STEROIDS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Steroids: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83640-X 1. Steroids-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on steroids. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON STEROIDS ................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Steroids ....................................................................................... 10 E-Journals: PubMed Central ..................................................................................................... 120 The National Library of Medicine: PubMed .............................................................................. 128 CHAPTER 2. NUTRITION AND STEROIDS ....................................................................................... 261 Overview.................................................................................................................................... 261 Finding Nutrition Studies on Steroids ...................................................................................... 261 Federal Resources on Nutrition ................................................................................................. 266 Additional Web Resources ......................................................................................................... 266 CHAPTER 3. ALTERNATIVE MEDICINE AND STEROIDS ................................................................. 271 Overview.................................................................................................................................... 271 The Combined Health Information Database............................................................................. 271 National Center for Complementary and Alternative Medicine................................................ 272 Additional Web Resources ......................................................................................................... 275 General References ..................................................................................................................... 296 CHAPTER 4. DISSERTATIONS ON STEROIDS ................................................................................... 297 Overview.................................................................................................................................... 297 Dissertations on Steroids ........................................................................................................... 297 Keeping Current ........................................................................................................................ 302 CHAPTER 5. CLINICAL TRIALS AND STEROIDS ............................................................................. 303 Overview.................................................................................................................................... 303 Recent Trials on Steroids ........................................................................................................... 303 Keeping Current on Clinical Trials ........................................................................................... 318 CHAPTER 6. PATENTS ON STEROIDS.............................................................................................. 321 Overview.................................................................................................................................... 321 Patents on Steroids .................................................................................................................... 321 Patent Applications on Steroids................................................................................................. 405 Keeping Current ........................................................................................................................ 441 CHAPTER 7. BOOKS ON STEROIDS ................................................................................................. 443 Overview.................................................................................................................................... 443 Book Summaries: Federal Agencies............................................................................................ 443 Book Summaries: Online Booksellers......................................................................................... 447 The National Library of Medicine Book Index ........................................................................... 467 Chapters on Steroids .................................................................................................................. 468 CHAPTER 8. MULTIMEDIA ON STEROIDS ...................................................................................... 473 Overview.................................................................................................................................... 473 Video Recordings ....................................................................................................................... 473 Audio Recordings....................................................................................................................... 475 Bibliography: Multimedia on Steroids ....................................................................................... 475 CHAPTER 9. PERIODICALS AND NEWS ON STEROIDS ................................................................... 477 Overview.................................................................................................................................... 477 News Services and Press Releases.............................................................................................. 477 Newsletter Articles .................................................................................................................... 482 Academic Periodicals covering Steroids..................................................................................... 482 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 483 Overview.................................................................................................................................... 483 U.S. Pharmacopeia..................................................................................................................... 483 Commercial Databases ............................................................................................................... 487
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Researching Orphan Drugs ....................................................................................................... 488 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 491 Overview.................................................................................................................................... 491 NIH Guidelines.......................................................................................................................... 491 NIH Databases........................................................................................................................... 493 Other Commercial Databases..................................................................................................... 496 The Genome Project and Steroids .............................................................................................. 496 APPENDIX B. PATIENT RESOURCES ............................................................................................... 501 Overview.................................................................................................................................... 501 Patient Guideline Sources.......................................................................................................... 501 Associations and Steroids .......................................................................................................... 509 Finding Associations.................................................................................................................. 509 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 511 Overview.................................................................................................................................... 511 Preparation................................................................................................................................. 511 Finding a Local Medical Library................................................................................................ 511 Medical Libraries in the U.S. and Canada ................................................................................. 511 ONLINE GLOSSARIES................................................................................................................ 517 Online Dictionary Directories ................................................................................................... 517 STEROIDS DICTIONARY .......................................................................................................... 519 INDEX .............................................................................................................................................. 667
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with steroids is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about steroids, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to steroids, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on steroids. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to steroids, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on steroids. The Editors
1 From
the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON STEROIDS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on steroids.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and steroids, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “steroids” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Use of Anabolic Steroids in HIV Disease Source: STEP Perspective; Vol. 5, No. 2. Contact: Seattle Treatment Education Project, 1123 E John St, Seattle, WA, 98102, (206) 329-4857, http://www.thebody.com/step/steppage.html. Summary: This journal article discusses the use of anabolic steroids in the treatment of HIV disease. It defines steroids and explains biologic and synthetic compounds and their functions. It mentions ongoing studies of steroid use to combat fatigue and weakness and suggests that until more results are available, physicians are likely to be wary of prescribing steroid therapy.
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Ovarian Steroids and the Brain: Implications for Cognition and Aging Source: Neurology. 48(Supplement 7): S8-S15. May 1997. Summary: This journal article describes neural actions of gonadal hormones on nonreproductive brain structures and processes, with particular emphasis on the effects of estrogen and progestin on the hippocampal formation and basal forebrain of the rat. These brain structures play a prominent role in learning and memory, and are sites of neural degeneration in Alzheimer's disease and other dementing illnesses. The article also discusses ovarian steroid influences on the midbrain and brainstem monoaminergic systems, in light of their widespread involvement with brain functions that subserve movement and affective states. 90 references.
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Corticosteroids in Rheumatic Disease Source: Postgraduate Medicine. 103(2):137,140-142; February 1998. Summary: This journal article for health professionals discusses the use of steroid therapy in rheumatic disease. The article describes the anti-inflammatory and immunosuppressive effects of corticosteroids, and it explains how to administer them, focusing on a single daily dose, split doses, or alternate day dosing. It also presents an approach to prescribing corticosteroids that accounts for selecting the initial dose, tapering doses, using local or topical steroids whenever possible, and considering the use of corticosteroid-sparing agents in patients who appear dependent on corticosteroids. 12 references.
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New Steroids for Inflammatory Bowel Disease Source: Inflammatory Bowel Diseases. 1(2): 135-141. Summer 1995. Summary: This article reviews the use of glucocorticosteroids (GCS) in inflammatory bowel disease (IBD). The author notes that the antiinflammatory effects of GCS are unsurpassed by those of any other type of drug, but the beneficial effects are often offset by troublesome, and sometimes irreversible, systemic side effects. Improved GCS have been developed with the aim of obtaining improved topical action, with reduced systemic side effects. A high tissue uptake and a high affinity for the GCS-receptor, in combination with a rapid and extensive biotransformation in the liver, are key prerequisites. Budesonide appears to be the most promising of the new topical GCS for IBD. In enema form, it is already in clinical use for active distal ulcerative colitis (UC). Oral, slow release preparations of budesonide are efficacious in the treatment of active ileocecal Crohn's disease (CD), causing less suppression of endogenous plasma cortisol levels than does oral prednisolone, and giving rise to fewer and less severe side effects. Budesonide may also have a role in preventing clinical relapse in certain groups of patients with CD, and is currently under evaluation for extensive and left-side UC. The author concludes that future development of GCS for IBD includes factors such as improved topical delivery systems, enhanced tissue uptake, and even more extensive first pass metabolism. 1 table. 63 references. (AA-M).
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Steroids OK in Alcoholic Hepatitis Source: Medical World News. 31(1): 11. January 8, 1990. Summary: Corticosteroid therapy can reduce mortality significantly in a select group of acute alcoholic hepatitis patients, according to a meta-analysis of almost a dozen controlled trials. Results from some of those trials that suggested no such benefit can be explained by poor study design. Failing to exclude patients with active gastrointestinal
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bleeding accounts for most conclusions that there is no mortality reduction. Neglecting to distinguish patients who did not have hepatic encephalopathy may also have misled researchers, as corticosteroids appear to actually increase mortality in such patients. However, corticosteroids' long-term effects need further study. •
Angiotensin Antagonists and Steroids in the Treatment of Focal Segmental Glomerulosclerosis Source: Seminars in Nephrology. 23(2): 219-228. March 2003. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: The use of ACE inhibitors, along with good blood pressure control, have been shown to significantly decrease the level of proteinuria (protein in the urine) and slow the progression of renal (kidney) insufficiency in patients with nondiabetic glomerular disease including focal segmental glomerulosclerosis (FSGS). This article considers this treatment strategy, noting that this should be part of the therapeutic approach for all proteinuric patients with FSGS; should be considered the mainstay of therapy for patients with FSGS secondary to conditions associated with hyperfiltration or reduced nephron mass; and should be used for those patients with nonnephrotic primary FSGS. However, nephrotic patients with primary FSGS may continue to have marked proteinuria and progression of renal disease despite these measures and thus require a more aggressive approach with the use of steroids and immunosuppressive agents. Although primary FSGS was once thought to be a steroid-nonresponsive lesion, recent experience has provided a note of optimism in the use of steroids and immunosuppressive agents in treating this otherwise progressive glomerulopathy. As a result, a course of steroid therapy in primary FSGS is now warranted in nephrotic patients with reasonably well preserved renal function in whom it is not otherwise contraindicated. 7 tables. 90 references.
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Primum Non Nocere: Should Adults With Idiopathic FSGS Receive Steroids?. (commentary) Source: Seminars in Nephrology. 23(2): 229-233. March 2003. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Corticosteroids have been widely recommended for the treatment of patients with idiopathic (of unknown cause) focal segmental glomerulosclerosis (FSGS), despite the lack of evidence-based data to support the use of steroids in this disease. This commentary article considers the limitations apparent in the published studies. The studies primarily have been retrospective, have included few patients, and have not been uniform with respect to the steroid treatment protocol. Furthermore, side effects associated with corticosteroid use have not been well documented. The Glomerular Disease Collaborative Network's experience with steroids in idiopathic FSGS has shown a low rate of remission even when steroids were used in the recommended doses and for prolonged periods. The authors discuss recommendations regarding a specific subset of patients who may benefit from steroid treatment. The authors conclude that the controversies regarding steroids in idiopathic FSGS will only be resolved with data from controlled clinical trials. 2 tables. 26 references.
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Basic Facts About Steroids Source: For Patients Only. 6(1): 13, 24. January-February 1993. Summary: This brief article describes the uses and complications of steroids, the drugs used to treat many medical conditions, including kidney transplantation. Topics include the positive effects of steroids; their use with immunosuppressive agents including cyclosporine and azathioprine; and symptoms of steroid complications, including blood glucose problems in patients with diabetes, fluid retention and weight gain, and indigestion. The author stresses that close medical supervision of treatment and knowledge of the signs of potential problems can minimize side effects of these drugs.
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Supplemental Corticosteroids for Dental Patients with Adrenal Insufficiency: Reconsideration of the Problem Source: JADA. Journal of the American Dental Association. 132: 1580-1587. November 2001. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Dental patients with primary or secondary adrenal insufficiency (AI) may be at risk of experiencing adrenal crisis during or after invasive dental procedures. Since the mid 1950s, supplemental steroids in rather large doses have been recommended for patients with AI to prevent adrenal crisis. This continuing education article reports on a study undertaken to evaluate the need for supplemental steroids in these patients. In this study, the authors searched the literature from 1966 to 2000 using MEDLINE and textbooks for information that addressed AI and adrenal crisis in dentistry. Reference lists of relevant publications and review articles also were examined for information about the topic. The review identified only four reports of purported adrenal crisis in dentistry. Factors associated with the risk of adrenal crisis included the magnitude of surgery, the use of general anesthetics, the health status and stability of the patient, and the degree of pain control. The limited number of reported cases strongly suggests that adrenal crisis is a rare event in dentistry, especially for patients with secondary AI, and most routine dental procedures can be performed without glucocorticoid supplementation. 2 figures. 1 table. 62 references.
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Topical Corticosteroids in Association with Miconazole and Chlorhexidine in the Long-Term Management of Atrophic-Erosive Oral Lichen Planus: A PlaceboControlled and Comparative Study Between Source: Oral Diseases. 5(1): 44-49. January 1999. Contact: Available from Stockton Press. Marketing Department, Houndmills, Basingstoke, Hampshire RG21 6XS, United Kingdom. (800) 747-3187. Website: www.stockton-press.co.uk. Summary: This article reports on a study undertaken to evaluate the efficacy of a combination of topical corticosteroids with topical antifungal drugs in the treatment of atrophic-erosive forms of oral lichen planus (OLP). The study population consisted of 60 patients with OLP subdivided into three groups matched for sex and age. The first group (n = 25) received 0.05 percent clobetasol propionate ointment; and the second group (n = 24) received 0.05 percent fluocinonide ointment; both groups also received antifungal treatment consisting of miconazole gel and 0.12 percent chlorhexidine mouthwashes. The third group (n = 11), the placebo group, received only a plain ointment (hydroxyethyl cellulose gel), and antifungal treatment as above. All the
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treatment regimens were carried out for 6 months; each patient was examined every 2 months and for a further 6 months of follow up after active treatment. All patients treated with clobetasol and 90 percent of the patients treated with fluocinonide witness some improvement, whereas in the placebo group only 20 percent of patients improved. However, when considering complete responses, only clobetasol gave significantly better results than placebo. Clobestasol resolved 75 percent of the lesions whereas fluocinonide was effective in 25 percent of cases and placebo in none. Similar results were obtained for symptoms. None of the treated patients contracted oropharyngeal candidiasis. After 6 months of follow up, 65 percent of the clobetasol treated group and 55 percent of the fluocinonide group were stable. Estimation of plasma cortisol levels showed no significant systemic adverse effects of clobetasol or fluocinonide. The authors conclude that a very potent topical corticosteroid such as clobetasol may control OLP in most cases, with no significant adrenal suppression or adverse effects. Moreover, a concomitant antifungal treatment with miconazole gel and chlorhexidine mouthwashes is a useful and safe prophylaxis agent against oropharyngeal candidiasis. 2 figures. 3 tables. 33 references. •
Review: Corticosteroid Therapy Does Not Reduce the Rate of Relapse in Crohn Disease (commentary) Source: ACP Journal Club. 130(2): 36. March-April 1999. Contact: Available from American College of Physicians-American Society of Internal Medicine (ACP-ASIM). 190 North Independence Mall West, Philadelphia, PA 191061572. Summary: This brief article offers a summary of a recent research study, with an accompanying commentary. The study was undertaken to determine whether conventional systemic corticosteroid therapy is effective and safe for the maintenance of clinical remission in Crohn disease; the study also investigated the long term toxicity of corticosteroid therapy. The literature was reviewed and a data extraction on methodologic quality, patient and disease characteristics, interventions, outcomes (at 6, 12, and 24 months), and adverse effects was performed. Of the 8 studies identified, 3 met the inclusion criteria (368 patients in each of the active drug and placebo groups). No study, individually or in combination, showed a reduction in the relapse rate of Crohn disease overall or at 6, 12, or 24 months. The commentary notes that although this rigorous meta analysis failed to identify a statistically significant benefit of glucocorticoid maintenance therapy, the pooled estimates of the treatment effect consistently showed a trend favoring the intervention over placebo. 2 references.
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Study Finds IV Cyclosporine To Be Effective in Steroid-Resistant Ulcerative Colitis Source: IBD Chronicle. 1(1): 1-2. May 1993. Contact: Available from Medical Information Services P.O. Box 1384, Ansonia Station, New York, NY 10023. Summary: This newsletter article reports on conferences and research related to inflammatory bowel disease. The article describes a study that found intravenous (IV) cyclosporine effective in steroid-resistant ulcerative colitis. In a double-blind study of 16 patients who had failed 10 days of therapy with parenteral steroids, 14 (88 percent) of those given cyclosporine (4 mg/kg/day) responded favorably, with a mean response time of 7.1 days. The intravenous route was chosen because oral cyclosporine is associated with erratic absorption and erratic blood levels in patients with bowel disease
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and diarrhea. The final section of the article explains how this research study confirms an earlier, pilot study of intravenous cyclosporine. •
Nonsteroidal Anti-inflammatory Drugs and Peptic Ulcer Disease: An Overview Source: Postgraduate Medicine. 89(7): 33-38, 40. May 15, 1991. Summary: This article reviews the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and gastroduodenal ulcers, as well as current data about prophylaxis against NSAID-induced ulceration. The mechanism of action of NSAIDs seems to be both topical damage to the mucosal barrier and the systemic effect of a reduction in levels of mucosal prostaglandins. Patients especially at risk are the elderly, those with concomitant debilitating disease, those with a history of ulcers, and those taking corticosteroids. The author discusses the use of histamine2 blockers and misoprostol to reduce the incidence of NSAID-induced ulcers. 1 table. 31 references. (AA-M).
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Drug Selection and the Management of Corticosteroid-Related Diabetes Mellitus Source: Rheumatic Disease Clinics of North America. 25(3): 489-505. August 1999. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article focuses on drug selection and the management of corticosteroidrelated diabetes mellitus. Glucocorticoid use is associated with the risk of hyperglycemia in patients who do not have diabetes mellitus and worsened glycemic control in people who have diabetes. The article begins with a discussion of the pathophysiology of impaired glucose tolerance and diabetes mellitus. This is followed by the identification of the mechanisms by which hyperglycemia occurs with glucocorticoid use and the patterns of hyperglycemia associated with glucocorticoid use. The article then presents data on the prevalence of hyperglycemia and discusses the rationale for treatment of glucocorticoid-induced hyperglycemia. Approaches to control of hyperglycemia are described, including employing nonpharmacologic measures such as diet therapy and regular exercise; using oral glucose lowering agents such as sulfonylureas, repaglinide, acarbose, biguanides, and thiazolidinediones; combining oral agents; and injecting insulin. The article then provides guidelines for management of glucocorticoid-related hyperglycemia based on the understanding of how glucocorticoids affect blood glucose, the mechanisms of action of glucose lowering agents, and professional experience in treating patients with glucocorticoid-related hyperglycemia. 1 figure. 2 tables. 69 references.
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Management of Steroid-Sensitive Nephrotic Syndrome and in Children with Type 1 Diabetes Source: Pediatric Nephrology. 17(5): 351-354. May 2002. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: This article reports the cases of four children with steroid-sensitive nephrotic syndrome (SSNS) coexisting with type 1 diabetes. This number is higher than expected according to the estimated prevalence rates for each disease separately. In three of the children, diabetes preceded nephrotic syndrome (NS) and in one child it developed almost simultaneously. None of the patients had hypertension (high blood pressure) or retinopathy (eye disease). Two had a renal (kidney) biopsy; in one it was compatible with minimal change histology (MCH) and the other had MCH and early diabetic
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nephropathy (kidney disease due to diabetes) changes. The authors also briefly report on 12 previously described cases with biopsy. In 11 of these 12 previously reported cases, the biopsy showed MCH. In none was treatment influenced by biopsy results. However, experience suggests that daily steroid taper allows easier glycemic control than alternate day steroids. The authors conclude that the indications for a kidney biopsy in nephrotic children with and without insulin dependent diabetes mellitus should be similar. 1 table. 19 references. •
Levamisole: Adjunctive Therapy in Steroid Dependent Minimal Change Nephrotic Children Source: Pediatric Nephrology. 17(5): 355-358. May 2002. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: In children with minimal change nephrotic syndrome (MCNS, a type of kidney disease), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. In addition, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. This article reports on the authors' experience in treating 20 steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3 to 15 years; 16 were boys and 4 were girls. Remission was first induced by steroids, then levamisole was added in a dose of 2.5 milligrams per kilogram body weight on alternate days for 6 months. During this period, the authors attempted to withdraw steroids completely and maintain patients on levamisole alone. Patients were followed for the occurrence of relapse and side effects. In 11 of 20 children (55 percent), steroids were successfully stopped for more than 2 weeks. At the end of the 6 month treatment period (i.e., after 4 months of steroid discontinuation), 10 patients (50 percent) were maintaining remission on levamisole alone. At the end of 12 months (i.e., after 6 months of levamisole discontinuation), five patients (25 percent) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. The authors conclude that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. 1 figure. 2 tables. 20 references.
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Response of Balanitis Xerotica Obliterans to Local Steroid Application Compared with Placebo in Children Source: Journal of Urology. 165(1): 219-220. January 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800)638-3030 or (301) 714-2334. Fax (301) 824-7290. Website: www.lippincott.com. Summary: Balanitis xerotica obliterans is a chronic inflammatory disease of unknown etiology that may affect the foreskin, glans penis, frenulum, and meatus or urethra in males. Presenting symptoms include sudden phimosis (tightness and inability to retract the foreskin) in a previously retractable foreskin, decreased glans sensation, meatal stenosis, dysuria, and urinary obstruction. This article reports on a study that evaluated the clinical effectiveness of topical steroid application for balanitis xerotica obliterans in children and analyzed the association of any clinical response with histological findings. The double blind, placebo controlled, randomized study included 40 boys in whom
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balanitis xerotica obliterans was diagnosed clinically. The severity of phimosis was graded into 4 groups and patients were randomized to receive the topical application of 0.05 percent mometasone furoate or placebo. After 5 weeks, phimosis severity was reevaluated and all patients underwent circumcision. Surgical specimens were histologically typed as an early, intermediate, or late form of balanitis. Seven patients were withdrawn from the study. In the steroid group, 7 boys had clinical improvement, and 10 had no change. Histological study showed an early, intermediate and late form of balanitis xerotica obliterans in 5, 5, and 7 cases, respectively. Of cases with clinical improvement, 5 were the early and 2 the intermediate type. In the placebo group, 5 cases worsened clinically and 11 did not change. The authors conclude that applying a potent topical steroid affects improvement in balanitis xerotica obliterans in the histologically early and intermediate stages of disease and may inhibit further worsening in the late stage. 1 figure. 14 references. •
Risk Factors for Steroid Dependency in Children with Idiopathic Nephrotic Syndrome Source: Pediatric Nephrology. 16(12): 1049-1052. December 2001. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: Minimal change disease, the most common cause of idiopathic nephrotic syndrome (INS) in children, has a high relapse rate, with approximately half of patients developing steroid dependency. This article reports on a study aimed at determining the predictive risk factors for the development of this steroid dependency. The retrospective study followed 123 children with steroid-responsive INS followed for at least 6 months between December 1974 and December 1999. The following parameters were studied: age at onset, gender, race, microscopic hematuria (blood in the urine) at onset, atopy (allergic reactions), concomitant upper respiratory tract infections (URTI) during relapses, and days to remission with initial steroid therapy. Of the 91 children who fulfilled the inclusion criteria, 61.5 percent became steroid dependent. Analyses revealed that initial remission time of 9 or more days and concomitant URTI during relapses were significant predictors of steroid dependency. By identifying those children with predictive factors of steroid dependency, the clinician will be better able to plan the long term management of these patients and reduce the morbidity seen with the frequent relapses and steroid treatment, in a disease that is otherwise associated with a favorable prognosis. 2 figures. 2 tables. 18 references.
Federally Funded Research on Steroids The U.S. Government supports a variety of research studies relating to steroids. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions.
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to steroids. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore steroids. The following is typical of the type of information found when searching the CRISP database for steroids: •
Project Title: 5 LIPOXYGENASE IN BONE Principal Investigator & Institution: Bonewald, Lynda F. Lefkowitz Professor; Oral Biology; University of Missouri Kansas City Kansas City, MO 64110 Timing: Fiscal Year 2001; Project Start 01-MAY-1993; Project End 31-AUG-2003 Summary: The underlying hypothesis for this application is that metabolites of the enzyme 5-lipoxygenase (5LO) play an important role in bone by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. 5LO metabolites of arachidonic acid may also be partially responsible for the bone loss which occurs due to estrogen deficiency. The specific aims of the proposal are: 1. To determine if the osteoclast is a producer of 5LO metabolites. 2. To determine the effects of 5LO metabolites on osteoblast function. 3. To characterize the dynamic and static features of bone in the 5LO knockout mice, and 4. To determine if 5LO plays a role in the increased bone loss associated with estrogen withdrawal. For Specific Aim 1, in situ hybridization for 5LO mRNA expression in bone and bone cells and quantitation of 5LO metabolite production by isolated osteoclasts will be performed. To determine if bone resorbing agents regulate mRNA and protein for 5LO, ribonuclease protection assays, immunoprecipitation, and immunoblotting will be performed. For Specific Aim 2, the effects of 5LOand bone-like nodule formation will be tested, as well as effects one bone formation in calvarial organ cultures. Osteoblast function in 5LO knockout animals will be compared to osteoblast function in wild- type animals. As the 5LO knockout mice have increased cortical bone, Specific Aim 3 will be performed to determine if this increase in bone is due to a decrease in osteoblast numbers or activity, an increase in osteoblast function, or a combination. The biomechanical properties of these bones will also be determined. In Specific Aim 4, it will be determined if 5LO metabolites mediate the effects of estrogen withdrawal by comparing bone loss in ovariectomized 5LO knockout mice with their wild-type controls. The proposed studies will provide important new insights into the role of 5LO metabolites in bone-a research are which is so far relatively unexplored. These studies may have clinical relevance to bone diseases such as osteoporosis and bone loss due to inflammatory conditions. Hence, these studies may also have profound implications for the increasing number of asthmatic patients who are currently being treated with steroids and 5LO inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: 500 MHZ NMR SPECTROMETER Principal Investigator & Institution: Franck, Richard W. Professor; Chemistry; Hunter College 695 Park Ave New York, NY 10021 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): Hunter College requests funding for a 500 MHz NMR spectrometer equipped with field gradients and reverse detection capabilities, and designated for the study of small bioactive organic molecules. The instrument will serve
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as a shared facility for users at Hunter and other City University of New York (CUNY) campuses. The routine availability of high-field NMR is a sine qua non for organic chemistry research of biological materials. The new NMR is necessary to prove structures and analyze conformations of materials important in health-related research projects at CUNY which involve chemoprotective agents from tropical fruits and vegetables, porphyrinic materials for photodynamic therapy, C-glycosyl lipids with antitumor activity, glycomimetics as potential drugs, lipids and steroids used in signaling, chemically-modified nucleosides, and peptides for nuclear medicine. An important capability of the new NMR will be its routine use in experiments such as HMQC and HMBC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A PROTEOMICS
GENETIC
SCREEN
FOR
PROTEIN
EVOLUTION
AND
Principal Investigator & Institution: Cornish, Virginia W. Chemistry; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): This grant application describes a cell-based assay for detecting molecular recognition and catalysis that can be used to evolve proteins with new functions. There is tremendous interest in being able to engineer proteins with new specificities and new activities for use as reagents for biomedical research, diagnostics and therapeutics for the health care community, and tools for the pharmaceutical industry. The screen builds from existing technology for dimerizing proteins inside a cell with dimeric ligands via the ligands' receptors (CIDs). By replacing one of the ligand-receptor pairs with potential binding partners, binding can be detected. By replacing the chemical linker between the two ligands with a bond and adding an enzyme, the assay can be used as a read-out for bond formation or bond cleavage. In Preliminary Results dexamethasone-methotrexate CIDs with non-cleavable and cleavable linkers have been developed. Aim 1 outlines our plans to evolve a protein receptor for estradiol that can be used in medical diagnostics for monitoring estrogen levels in women. We have developed a docking algorithm to pick several monomeric proteins from the PDB as the starting protein scaffolds. We plan to mutagenize these proteins using existing methods and then select for high affinity, specific receptors by screening for binding to estradiol and against binding to other common steroids. Aim 2 describes our plans to modify the yeast two-hybrid assay to detect catalysis and then evolve a penicillin-binding protein into a cephalosporinase enzyme. Penicillin-binding proteins are the target of penicillin antibiotics and are believed to be the evolutionary precursors of cephalosporinases, the bacterial resistance enzymes that hydrolyze and inactivate these antibiotics. Because of the evolutionary relationship, the PBPs present a tractable first target for enzyme evolution. Moreover, this project should provide insight into how bacteria evolve antibiotic resistance and the mechanism by which the resistance enzymes hydrolyze the antibiotic. Finally, in Aim 3, we propose to develop a bacterial CID so that future protein evolution experiments can be carried out in bacteria. Bacteria have faster doubling times and higher transformation efficiencies than yeast, and so a bacterial CID system should facilitate the evolution experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A NEW NEUROENDOCRINE MODEL OF SEASONAL BEHAVIORS Principal Investigator & Institution: Mendonca, Mary T. Biological Sciences; Auburn University at Auburn Auburn University, AL 36849
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Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 30-JUN-2004 Summary: (adapted from applicant's abstract): Comparative studies shed light on alternate neuroendocrine mechanisms underlying reproduction and its attendant sexual behaviors. By exploring alternate mechanisms and comparing them to the established paradigm, one can illuminate which neural substrates are basic and critical tot he expression of these behaviors. Bats are the second most prolific radiation of mammals yet they remain relatively unstudied. They display great diversity in their reproductive patterns and vespertilionid bats, in particular, constitute an excellent alternative model system to study neuroendocrine mechanisms affecting reproductive behavior due to unique features of their life history. They 1) have a dissociated pattern of reproduction, mating when gonads are regressed and sex steroids are basal, and 2) are heterothermic, with arousal from hibernation being a potent and rapid stimulator of sexual behavior. Therefore, an external cue (i.e. temperature change) appears to activate sexual behavior independent of the classical role played by sex steroids. Preliminary data indicate that male and female big brown bats, Eptesicus fuscus, a vespertilionid, can mate months (at least 6 for males and 18 for females) after gonadectomy when given the proper temperature regimen. The specific research objectives of this proposal are to test the hypotheses that this species has 1) become relatively (if not completely) independent of sex steroids as an activator of reproductive behavior and sexual behavior. If these hypotheses are supported, the PI proposes a starting point to explore which alternative neuroendocrine mechanisms may be replacing the classic mechanism of sex steroid activation of sexual behavior. To achieve these objectives, two intertwined lines of research will be established. One will document the extent to which the expression of sexual behavior by males and females is independent from gonadal sex steroids by removal of gonads at different points in the seasonal cycle as well as removal of possible extragonadal sources of sex steroids. Replacement sex steroids will be given at these points to determine their efficacy in re-instating the behavior in animals. The second line will document the pattern of torpor and arousal and how sex steroids change in relation to these states. It will also determine what degree of exposure to low temperature (or entrance into a torpid state) insures the expression of mating and how this is modified by the presence or absence of sex steroids. Preliminary experiments will administer intracerebroventricular doses of GnRH antagonist and agonist to begin testing if this is a potential neuroendocrine mechanism linking arousal from hibernation and mating in this species. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADOLESCENT ANABOLIC STEROIDS, VASOPRESSIN AND AGGRESSION Principal Investigator & Institution: Melloni, Richard H,. Assistant Professor; Psychology; Northeastern University 360 Huntington Ave Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-1996; Project End 31-MAR-2008 Summary: (provided by applicant): Recently much public attention has been drawn to the issue of youth violence, particularly that associated with drug abuse. It is well documented that anabolic steroid use in adolescent teenagers is associated with a higher incidence of aggression and violence. However, the basic biobehavioral processes underlying the development and maintenance of the aggressive phenotype following adolescent anabolic steroid exposure remain unknown. Recently, we have used peripubertal Syrian hamsters (Mesocricetus auratus) as an "adolescent" animal model to show that anabolic steroid exposure during this period facilitates the development of an aggressive behavioral phenotype when tested as young adults. In addition, aggressive,
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anabolic steroid-treated adult animals present with altered brain chemistry; specifically, arginine vasopressin and serotonin afferent innervation to the anterior hypothalamic brain region implicated in the regulation of offensive aggression. The research outlined in this proposal is a continuation of our work on adolescent anabolic steroids and the behavioral neurobiology of aggression. These studies examine the biobehavioral effects of adolescent anabolic steroid exposure on aggression permanence and the anatomy and function of the anterior hypothalamic arginine vasopressin and serotonin neural network controlling this behavior in hamsters. It is hypothesized that adolescent anabolic steroids disrupt the signaling equilibrium between anterior hypothalamic arginine vasopressin and serotonin, facilitating the development and maintenance of the aggressive phenotype. It is possible that this disruption occurs at the level of the signal molecules themselves, and/or at the level of their receptors. To test this, we are asking two questions: (1) how has adolescent anabolic steroid exposure affected the arginine vasopressin and serotonin neural systems and (2) are the changes in behavior and neurobiology permanent? Completion of the proposed research should provide new insight into the basic biobehavioral processes regulating adolescent anabolic steroidinduced aggression. This knowledge could provide a scientific basis for the rational treatment of aggressive, anabolic steroid abusers and a better understanding of the behavioral and biological changes that may predispose young individuals to behave in a self-destructive or violent manner later in life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADOLESCENT ASTHMA SELF-MANAGEMENT TELEHEALTH APPLICATION Principal Investigator & Institution: Cohen, Marc; President; Sixtyseven Kilohertz, Inc. 1801 Maple Ave, Ste 2307 Evanston, IL 60201 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): We theorize that a low-intensity disease selfmanagement intervention consisting of asthma related health messages based on the Health Belief Model and delivered regularly over an extended period via a personal digital music player, can improve asthma outcomes among low-income urban adolescents. The objective of the proposed study is to test this hypothesis and to obtain proof-of-principle that will serve as the basis for further research. Almost 25% of students in Chicago Public Schools located in high poverty neighborhoods have been diagnosed with asthma. Less than half of these children exhibit appropriate use of inhaled steroids or maintain regular visits with a physician. Through a grant from the National Institute on Drug Abuse, Sixty-Seven Kilohertz, Inc. and Northwestern University have developed a novel messaging platform for anti-drug PSAs called X-CD. X-CD delivers updateable content via long-distance wireless transmission to personal (Walkman type) digital music players. Because it does not require a PC or Internet connection, X-CD is an appropriate telehealth medium for the target population since most low-income urban adolescents do not have regular access to these tools. We have designed and built a personal CD player to work with the X-CD technology platform. However we do not believe this device is optimal for the target population since CDs may not be the primary music medium for low-income adolescents due to their high cost. Therefore, we will adapt the X-CD player to a personal music player that can tune commercial radio stations and receive, store and play MP3 music tracks that we transmit to the players. We propose to conduct a 24-week application efficacy study with nonrandomized experimental and control groups, 20-30 subjects in each. Participants will be recruited from the pediatric asthma clinic at Cook County Hospital. Outcome measures
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including: number and severity of asthma attacks, and disease knowledge and asthma self-management skills, will be assessed prior to the intervention and at 2, 6, 12, 18, and 24 weeks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANABOLIC STEROIDS AND CEREBELLAR GABAA RECEPTORS Principal Investigator & Institution: Yang, Paul; Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 01-OCT-2001 Summary: Anabolic-androgenic steroids (AAS) are an increasingly popular substance of abuse among adolescents, as well as elite athletes. The actions of AAS in the central nervous system are poorly understood, however, recent studies in rodents indicate that AAS induce rapid and reversible modulation of gamma-aminobutyric acid type A (GABAA) receptor-mediated currents in neurons of forebrain regions of both prepubertal and adult animals. Moreover, the ability of AAS to modulate currents in the forebrain is region- specific and depends on receptor subunit composition. The expression of GABAA receptors comprising different subunit isoforms is heterogeneous throughout the brain and regulated both in a region-specific and developmental manner. Therefore, understanding differential AAS modulation of GABAA receptors composed of different subunits establishes the essential groundwork for understanding the actions of AAS in the central nervous system. The cerebellum is an ideal system for allosteric modulation of GABAA receptors because the cell-specific patterns of expression of different subunits and the functional modulation of GABAA receptormediated currents by other modulators have been well characterized, especially in Purkinje and granule cells. In addition, the cerebellum is the essential structure in mediating motor memory and motor coordination, both of which may be affected during AAS. Using whole-cell patch-clamp recording techniques of neurons in acutely isolated brain slices, the ability of specific AAS to induce different patterns of modulation upon inhibitory postsynaptic currents (IPSCs) in Purkinje cells and granule cells of postnatal rats will be determined. Second, to correlate, at the single cell level, significant differences in the ability of AAS to modulate GABAergic IPSCs with cellspecific patterns of subunit gene expression, single cell RT-PCR will be used to detect the ratio of subunit families expressed. Finally, using ultrafast perfusion patch-clamp technique on recombinant GABAA receptors expressed in transfected cells, the subunit dependence of AAS IPSC modulation will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANABOLIC STEROIDS AND EXERCISE IN HEMODIALYSIS Principal Investigator & Institution: Johansen, Kirsten L.; Northern California Institute Res & Educ San Francisco, CA 941211545 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: The federally-funded End Stage Renal Disease program was initiated in 1972 with the goal of extending the lives of individuals with kidney disease and allowing them to return to the work force. Though dialysis has prolonged the lives of patients with ESRD, it has not produced the expected degree of occupational and physical rehabilitation. A recent study showed that more than one third of hemodialysis patients had a Karnofsky score below 70, meaning that they were unable to perform the normal activities of daily living without assistance. Investigation into the causes of this striking debility has been limited, but muscle atrophy and concomitant weakness probably
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contribute. Reduced lean body mass (LBM) and muscle weakness have been demonstrated in this population. Since muscle strength correlates with performance measures such as gait speed in elderly subjects, the reduction in LBM in dialysis patients may affect functional status, and treatments designed to increase muscle size and strength could be of benefit to such individuals. Both anabolic steroid treatment and resistance exercise training (RE) increase strength and muscle mass in healthy subjects. RE also resulted in improved functional status in frail elderly subjects. While there have been no reports of the effects of RE in patients on dialysis, we recently showed that nandrolone decanoate (ND), a 19-nortestosterone derivative, increased LBM and improved walking and stair-climbing time in patients on dialysis. Furthermore, ND was safe in this population and resulted in only occasional mild side effects. In the current application, we propose to perform two studies concurrently. In one, to elucidate the mechanisms of the muscle defects of dialysis patients, healthy control subjects and patients on dialysis will undergo measurement of physical activity levels, and of muscle size, strength, and oxidative capacity. In the second, we will determine whether RE and/or anabolic steroids can increase muscle size and improve muscle strength and physical performance in patients on hemodialysis. In a 12-week study, 80 hemodialysis patients will be randomly assigned to one of 4 groups as follows: ND, weekly ND injections; EX, resistance exercise training plus placebo injections; ND-EX, ND injections plus RE; and PL, placebo injections only. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF TEAM-BASED SUBSTANCE ABUSE PREVENTION Principal Investigator & Institution: Mackinnon, David P. Professor; Psychology; Arizona State University P.O. Box 873503 Tempe, AZ 852873503 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 31-JUL-2003 Summary: (adapted from Investigator's abstract) The purpose of this continuation proposal is to continue to complete and publish the evaluation of a prospective, randomized, study of the effects of the school-based anabolic steroid and other drug use prevention program, entitled ATLAS (Adolescents Training and Learning to Avoid Steroids). ATLAS is a social-influences based primary prevention program aimed at modifying those factors that increase the desire of young athletes to use anabolic steroids. In addition, nutrition and strength training alternatives to anabolic steroids are provided. The program uses peer leaders and coaches in a team-centered approach to exert positive peer pressure and role modeling. After one year, positive effects on selfreported steroid use, intentions to use steroids, nutrition behaviors, and many mediators of program effects were observed. 31 Portland, Oregon-area high school football teams were randomized to receive the ATLAS program (15 high schools) or a standard pamphlet on steroid use. Starting in the summer of 1994 with cohort 1, a total of four cohorts of all football players at these 31 high schools were measured for four years-- the last data collection was November, 1997. Over 4000 subjects are in this multiple wave longitudinal data set that includes questionnaire and anthropometric (e.g., height, weight, body fat, strength) measures. The data for the project were collected, cleaned and merged five months after funding for the grant expired. No new data collection is planned for this continuation proposal. We will apply recently developed statistical methods and software in the evaluation of program effects, mediation analysis to determine how the ATLAS program worked, moderator analysis to identify subgroups where the program is most or least effective, and etiological analysis to identify the precursors to steroid and other drug use. Advanced statistical methods including growth curve models, mixture models, multiple mediator models,
Studies 17
hierarchical linear models, missing data models, and models for categorical data will be applied across multiple waves and across each of the four cohorts. The overall purpose of the grant is to use advanced as well as more common statistical methods to extract the maximum important information from these data and publish the results. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIESTROGENS AND BREAST DENSITY IN PREMENOPAUSAL WOMEN Principal Investigator & Institution: Morrow, Monica; Professor; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001 Summary: Breast density is a major cause of the failure to detect breast cancer with screening mammography in pre-menopausal women. Tamoxifen is used for breast cancer risk reduction and treatment, but little is known about its effect on breast density, or the correlation between tamoxifen-induced changes in sex steroids and symptoms which decrease quality of life and limit the use of tamoxifen. The ideal agent would be one which decreased breast density without producing systemic effects. We propose to address this problem using full-field digital mammography to measure breast density reproducibility. The specific aims are: 1) to correlate changes in breast density with the hormonal changes throughout the menstrual cycle using a salivary assay for sex steroids. This study will determine whether this is a significant factor which must be controlled for in intervention studies; 2) To evaluate the alterations in breast density produced by tamoxifen, and correlate changes in steroid hormone levels with changes in quality of life; and 3) to examine the use of a topically applied anti- estrogen, 4hydroxytamoxifen, on breast density. The incidence of symptoms and changes in hormone levels will be assessed to determine the extent of systemic absorption and its clinical significance. This study will provide useful information to women about the scheduling of mammographic examinations; determine if tamoxifen reduces breast density, another potential benefit of the drug for high-risk women; and ascertain whether a local strategy of density reduction is effective without producing systemic symptoms. If so, this would offer a major opportunity to improve our ability to detect breast cancer in the female population as a whole. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASSESSMENT OF ANDROGENIC HORMONES IN PATIENTS WITH CORONARY HEART DISEASE Principal Investigator & Institution: Elam, Marshall B.; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001 Summary: This study is to determine if DHEA status predicts testosterone and estradiol levels, and will compare the relative strengths of the association of these gonadal sex steroids with CHAD to that observed with DHEA." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGICAL FOUNDATIONS OF VOCAL LEARNING Principal Investigator & Institution: Dooling, Robert J. Professor; Psychology; University of Maryland College Pk Campus College Park, MD 20742 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 30-JUN-2004
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Summary: The present proposal aims to understand the relationship between hearing, vocal development, and vocal learning in a small Australian parrot - the budgerigar or domesticated parakeet. Budgerigars learn new vocalizations throughout life with a capacity that may be unlimited. For a number of reasons, budgerigars provide a better animal model for studying some of the biological processes underlying human speech and language learning than the more well-studied songbirds. The present proposal involves a blend of behavioral physiological, and anatomical studies on hearing, perception, and the production of vocal signals, and the learning of new vocalizations through operant conditioning. Bringing vocal learning under operant control in an animal model provides a whole new range of opportunities to explore the relation between auditory perception and vocal production. Past auditory discrimination studies with simple and complex sounds have now led to a model of the budgerigar auditory system functions and is specialized for perceiving vocal signals and new experiments, using a linear systems approach, are now focused on testing aspects of that model. Vocal learning brought under operant control will test the role of auditory feedback, temporary threshold elevation, short-term memory, and short- term memory, and other behavioral mechanisms known to be involved in human speech and language. Achieving control over vocal learning is a major breakthrough and now allows a rigorous functional test of the role of the role various nuclei and pathways in the auditory vocal circuit suspected to be involved in vocal learning and auditory memory. Additional experiments are aimed at understanding the role of steroids in sex differences in vocal perception and vocal learning. Together, these experiments seek to identify and understand the basic biological principles that are capable of organizing and maintaining a complex, learned vocal communication system that remains plastic throughout adulthood. Results from these experiments should have relevance understanding the perception of complex natural sounds such as vocalizations ans speech, the effects of hearing (and hearing loss) on vocal learning, the design of sensorimotor interfaces and neural circuits that sustain complex learning, and the evolution of acoustic communication systems including human language. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGICALLY ACTIVE STEROID ANALOGS Principal Investigator & Institution: Hochberg, Richard B. Professor; Obstetrics and Gynecology; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-AUG-1984; Project End 31-JAN-2006 Summary: (Adapted from the Investigator's Abstract): Aim 1 is to synthesize 18F-labeled androgens for Positron Emission Tomography (PET) imaging of prostate cancer. The steroids include an active androgen as well as prohormones that are metabolically protected to maximize the biological signal. These steroids, labeled at C-7alpha with 18F, will be synthesized and tested for androgen receptor mediated concentration in the prostate of rats and rabbits. Aim 2 is to synthesize 18F and 123I labeled pyridyl and pyrimidyl N-substituted pyrazolo steroids based on the active glucorcorticoid, cortivazol. These steroids, containing N-activated leaving groups in their heterocyclic ring system, are designed specifically for isotope exchange reactions. The steroids are intended as PET or Single Photon Emission Tomography (SPECT) agents for imaging the glucocorticoid receptor rich region of the brain, the hippocampus. Aim 3 is to synthesize and test analogs of E2 that are potent estrogens and yet enzymatically labile which cause them to be converted rapidly into inactive metabolites. They are designed for use as local estrogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGY OF BREAST CANCERS ARISING IN OLDER WOMEN Principal Investigator & Institution: Benz, Christopher; Professor of Medicine; Buck Institute for Age Research Novato, CA 94945 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Recent analyses of nearly 4,000 primary breast tumors characterized by multiple prognostic and predictive biomarkers support the basic premise that breast cancer biology is age-dependent. While breast cancer biomarkers reflecting genetic instability and tumor growth as well as receptors for growth factors and sex steroids vary significantly with patient age, others reflecting tumor angiogenic, invasive and proteolytic potential show no age association, calling into question current cancer-aging hypotheses. Among known age-dependent breast cancer biomarkers some (e.g. p53- positivity, apoptotic index) exhibit most of their variation after age 50, others (tumor cell proliferative indices) show most of their variation before age 60, while others (ErbB2, EGFR, ER) change almost continuously with increasing age. Notably, the marked age-dependent rise in tumor estrogen receptor (ER) overexpression is unaccompanied by comparable changes in ER-inducible gene expression (e.g. PR, pS2, Bcl2) and associated with enhanced oxidant stress-activated signaling (P-Erk5) and transcription factor dysfunction (loss of Sp1 DNA-binding), supporting two corollaries to our fundamental breast cancer and aging premise: i) age affects breast cancer biology even among histologically similar ER-positive, nodenegative breast cancers, and ii) altered protein structure and function linked to oxidative stress and aging appear to clinically and biologically distinguish subsets of ER-positive breast cancers. To mechanistically distinguish ER-positive breast cancer subsets associated with aging, we will evaluate nucleic acid (DNA, RNA) and protein extracts from up to 264 cryobanked ER-positive node-negative ductal cancers arising in old (greater than age 70) vs. young (less than age 40) patients, with these age-grouped cases balanced for known risk factors and biomarkers linked to breast cancer incidence and biology. Since old and young ER-positive tumors are expected to use different p53dependent and p53-independent mechanisms for growth dysregulation, CGH microarrays, PCR-based microsequencing and methylation status determinations will be used to document the extent and type of chromosomal gains/losses, p53 mutations, and epigenetic silencing defects in p21WAF1 and p14ARF/p161NK4 loci associated with higher tumor proliferative rates and distinguishing old vs. young cases. Since subgroups of ER-positive tumors increase differently with age and are associated with different clinical outcomes, RNA expression microarrays will be used to identify specific transcript profiles clustering with higher tumor proliferative rates within and between the age-defined tumor groups. Lastly, protein extracts from these same tumor groups, as well as from oxidant stress-induced breast cancer cell line models, will be used to confirm that critical differences defining the biology of ER-positive breast cancers arising in older patients include the enhanced role of tumor-promoting and oxidant stress-associated cell signaling (P-Erk5, p66Shc), intracellular protein damage (carbony content), and loss of Sp1 DNA-binding and ER/Sp1-driven gene expression. These DNA, RNA and protein studies are expected to identify new breast cancer biomarkers that may be used to tailor age-specific therapeutics and improve our understanding of critical subcellular mechanisms affected by aging, oxidative stress and malignant transformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOMIMETIC FUNCTIONALIZATION OF STEROIDS Principal Investigator & Institution: Chruma, Jason J. Chemistry; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2002; Project Start 10-FEB-2003 Summary: (provided by applicant): The goal of this proposal is the development of artificial P-450 enzymes as a practical alternative to microbiological methods in the selective functionalization of steroids. Steroid pharmaceuticals play a prominent rote in the treatment of diseases ranging from arthritis to neuronal disorders. The continued identification of exciting biological activities from novel steroid natural products suggests that the potential for steroid scaffold-based drugs is far from being exhausted. The current manufacture of steroid medicinals relies heavily upon the ability of microorganisms to selectively oxidize steroid scaffolds. This proposal outlines strategies to efficiently synthesize novel sets of geometrically diverse hetero- and homogeneous catalysts that will mimic, and potentially surpass, the site-selective microbiological functionalization of steroids. In specific, groups of unique cyclophane thiols will be constructed in a modular fashion on polymer-support and then condensed with tetra(pentafluorophenyl)porphyrin (TFPP). These proposed cyclophanefluoroporphyrin conjugates were designed to address the limitations of current P-450 mimics, namely (1) the proclivity toward oxidative degradation and (2) the limited range of positions on the steroid scaffold that can be functionalized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CALCIUM AND POTASSIUM CHANNELS IN LYMPHOCYTE Principal Investigator & Institution: Rivera, Amelia; Universidad Central Del Caribe Bayamon, PR 009606032 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2005 Summary: The major goal of this project is to elucidate the mechanisms of non- genomic steroid effects in T lymphocytes. Non-genomic steroid actions have received much attention in the past decade. They are characterized by their rapid onset of action and by being independent of transcription and protein synthesis. Non-genomic steroid actions are ubiquitous and well documented. Steroid hormones have been shown by us and others to cause rapid changes in calcium signals in lymphocytes. These changes fall into the category of non- genomic steroid effects. In lymphocytes, initial calcium signaling upon TCR activation has been shown to occur by a two step process involving IP3 mediated release of calcium from internal stores and calcium influx through Ca2+ release-activated Ca2+ channels. This signaling cascade has been associated to tyrosine kinases in lipid rafts. Lipid rafts, or detergent insoluble microdomains, are surface membrane constituents that play important roles in signal transduction and membrane trafficking in lymphocytes and many other cells. We propose that non-genomic steroid actions are mediated by steroid association to the proteins of the lipid raft. The Specific Aims to be followed are: Specific Aim 1: Evaluate the non-genomic effects of the gonadal steroids on intracellular free Ca2+ levels in murine and human lymphoblastoid cell lines. Specific Aim 2: Determine the presence of caveolae and/or detergent insoluble microdomains (lipid rafts) in lymphoblastoid cell lines. Specific Aim 3: Correlate the presenc3e of caveolae and/or lipid rafts in l in lymphocytes with the non-genomic action of gonadal steroids on Ca2+ signaling. The results obtained in this project will contribute to our understanding of the cellular and subcellular mechanisms involved in signal transduction, non-genomic steroid action and for our understanding of the mechanisms involved in immunosuppression.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER, CATABOLIC STEROIDS, EXERCISE AND QUALITY OF LIFE Principal Investigator & Institution: Schwartz, Anna L. Associate Professor; Primary Care Nursing; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-MAR-2003 Summary: The purpose of this study is to compare the effects of two exercise interventions (aerobic and resistance exercise) on cancer-related fatigue (CRF, weakness, body mass, bone density and quality of life in cancer patients receiving catabolic steroids. The combination of CRF, weakness, physical decline, and debilitation are common and well- documented side effects of cancer treatment that affect a patient's quality of life during and after treatment, and result in loss of productivity. The primary specific aim of the study is to test the effects of two home-based exercise programs, aerobic exercise versus resistance exercise, on newly diagnosed cancer patients receiving chemotherapy regimens that include catabolic steroids. The secondary aims are to test the directional relationship between type of exercise, CRF, weakness, and quality of life. Eighty subjects will be enrolled and followed for 1 year. A randomized, clinical trials, repeated measures design will be used. Measures of CRF (Schwartz Cancer Fatigue Scale, Profile of Mood States fatigue and vigor subscales, and daily measure) and quality of life (Side Effect Symptom Checklist, Symptom Impact Profile subscales, and Positive Affect Negative Affect Scale) will be obtained at monthly intervals. Measures of weakness (1- repetition maximum test, DEXA scans of body mass) and quality of life (DEXA scans of bone density and the 12-minutes walking distance) that are likely to show smaller increments of change will be measured at 3 months. Analysis will be by intent to treated, blocking on gender and chemotherapy protocol. Repeated measures analysis will be used to determine the effects of the intervention on each of the study variables. Interventions that improve functional ability and prevent the long-term complications associated with catabolic steroids may help to control the side effects of treatment, improve quality of life, and have a positive impact on the cost of health care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIOTONIC STEROIDS FROM THE ADRENAL GLAND Principal Investigator & Institution: Doris, Peter A. Associate Professor; Human Genetics Center; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 30-JUN-2003 Summary: Regulation of the activity of sodium, potassium-ATPase (NKA, the sodium pump) is a critical element in the maintenance of extracellular fluid volume and blood pressure. When the enzyme is resident in its functional location in the cell membrane, regulation of the enzyme is possible at both the intracellular and extracellular surfaces. At the intracellular surface the enzyme is regulated by signals arising from cell surface receptors for humoral substances such as angiotensin II, dopamine and norepinephrine. There is now evidence that these signals alter the vectorial transport produced by NKA by changing its subcellular distribution (endosomal sequestration). At its extracellular surface, NKA projects a highly conserved cardiotonic steroid binding site which is an integral part of the enzyme and which serves no other function except to bind cardiotonic steroids with high affinity. Recent work in our laboratory and work by others in the field has defined the chemical identity of substances which bind to and inhibit the enzyme through the cardiotonic steroid receptor. We have shown that this
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inhibitor is an endogenous substance synthesized by the adrenal cortex. The present studies will further refine our understanding of the function of adrenocortical cardiotonic steroid. The present studies will further refine our understanding of the function of adrenocortical cardiotonic steroid. We will delineate important features of the biosynthetic pathway which leads to formation of the endogenous adrenal cardiotonic steroid. We will examine the role of cholesterol and cholesterol side chain cleavage in the metabolic pathway leading to the production of adrenal cardiotonic steroid. We will examine the control of activity in this novel steroidogenic surface receptors. Finally, we will examine and characterize the interaction between adrenal cardiotonic steroid and its receptor binding site on renal sodium, potassium-ATPase. We will also determine if the interaction with this site coordinates with regulation of ATPase activity by humoral substances and whether the mechanism of coordination occurs through increased sequestration of the receptor protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR AND ANTIEPILEPTIC DRUGS ON HIPPOCAMPAL NEURONS Principal Investigator & Institution: Kocsis, Jeffery D. Professor; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: Antiepileptic drugs act through a variety of mechanisms to modulate neuronal hyper-excitability. Their pharmacological effects can be mediated by direct interaction with ion channels or receptors, or by alteration in the mode or level of their expression. A key objective of the present study is delineation of acute effects of specific classes of antiepileptics and steroids on hippocampal neurons studied in tissue culture and in brain slice. Somatic conductances (Na+, Ca2+, K+ and GABA-mediated C1conductances) will be studied using patch clamp techniques on isolated CA1, CA3, and dentate neurons in culture. Intra-dendritic recordings will be obtained in a hippocampal slice preparation to study the actions of antiepileptics on modulating sustained repetitive firing of Na+-mediated dendritic action potentials, GABA-mediated dendritic inhibition and dendritic Ca2+ spikes. We will test the hypothesis that certain antiepileptics exert action on dendritic conductances which are not clearly discernable in somatic recordings. The effects of antiepileptics on the excitability of the nonmyelinated mossy fibers and Schaffer collaterals will be examined to determine if these agents can act by limiting conduction from dentate to CA3 and CA3 to CA1. Putative receptor proteins for steroids are expressed in restricted regions of hippocampus. Do appropriate steroid ligands acutely modulate voltage-gated ion channels or neurotransmitter action in neurons isolated from these regions? High resolution time-lapse video recording and laser confocal microscopy will be used to examine patterns of intracellular Ca2+ levels of hippocampal neurons in culture. Changes in [Ca2+]i will studied following exposure to the excitatory neurotransmitter glutamate. Patterns of change in [Ca2+]i will be compared between soma and dendrite from cells in different regions, and after antiepileptic and steroid application. A key question here is to determine if antiepileptics, or steroids can effect [Ca+]i by changing intracellular release or uptake. The present studies will focus on antiepileptic drug and steroid action of specific neurons in rat hippocampus studied in both culture and slice. The long-term objective of the proposed studies is to increase our understanding of ion channel organization and Ca2+ signalling in hippocampal neurons and to define the actions of certain anti-epileptics and steroids in modulating neuronal excitability in the hippocampus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR AND MOLECULAR MEDIATORS OF HANTAVIRUS INFECTION Principal Investigator & Institution: Klein, Sabra L. Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2007 Summary: Hantaviruses are zoonotic agents that are carried by a wide range of rodent host species, are geographically diverse, and cause human disease for which there is currently no cure. The primary goal of this proposal is to better elucidate the cellular and molecular mechanisms mediating host responses to hantavirus infection. Because the CDC classifies hantaviruses as potential biological agents, studies that examine the mechanisms mediating host susceptibility to infectior are required for developing adequate therapies against infection. Sex differences in hantavirus infection are documented in humans and in several rodent reservoir species in which more males are infected than females. Although sex differences in hantavirus infection may reflect dimorphisms in behaviors, such as aggression in rodents or occupation in humans, recent data from our laboratory illustrate that immune responses against infection and virus replication differ between the sexes. After inoculation with Seoul virus (i.e., the naturally occurring hantavirus in Norway rats), male rats exhibit higher antibody responses, shed virus longer and through more routes, and have more viral RNA copies present in target organs, such as the lungs, than females. The expression of antiviral transcriptional factors (e.g., eIF-2alpha, NF-KappaB, IRF, and STAT) is higher in females than males. Upregulation of transcriptional factors, e.g. NF-KappaB, in females may underlie the elevated expression of genes that encode for proinflammatory, chemotactic, and antiviral proteins in females compared with males. Sex differences in hantavirus infection may reflect the effects of steroid receptor signaling pathways on NF-KappaBmediated signal transduction. The primary aim of this research proposal is to test the hypothesis that steroid hormones, including androgens, estrogens, and glucocorticoids, mediate sex differences in Seoul virus infection through effects on cell signaling pathways. The aims of this proposal will be met by: 1) characterizing sex differences in the expression and translation of genes thal encode for proinflammatory, antiviral, and chemotactic proteins during the acute and persistent phases of infection; 2) manipulating sex steroids at different times during development, to determine if the expression and translation of genes that encode for proinflammatory, antiviral, and chemotactic proteins are influenced by sex steroids; and 3) assessing whether sex differences inthe expression and translation of genes that encode for proinflammatory, antiviral, and chemotactic proteins are mediated by dimorphisms in glucocorticoid receptor-mediated pathways. Taken together, these studies will provide a comprehensive analysis of how steroid hormones and genes that encode for immunoregulatory proteins interact to affect sex differences in phenotypic responses to infectious diseases and may assist in the development of treatments for qemorrhagic fever viruses that will be successful in both sexes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL CENTER-COPD CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Scharf, Steven M. Professor; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Chronic obstructive pulmonary disease is a major problem worldwide with increasing prevalence and morbidity/mortality. Current
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therapy is based on smoking cessation, maximizing lung function, treating infection and rehabilitation. The increase in knowledge about basic disease mechanisms affords the opportunity to explore new methods for treating this disorder. We propose the development of a clinical center at the University of Maryland to participate in the NIH COPD Clinical Research Network. In addition to describing the patient population and recruitment strategies, we present 2 model proposals for consideration by the network. The first proposal relies on recent findings that there is a strong inflammatory component in patients with end-stage COPD which may lead to weight loss, muscle wasting and increased mortality. A key inflammatory cytokine is tumor necrosis factor alpha (TNFalpha). We propose evaluating the effects of anti-TNFalpha therapy (inflixamab) in moderate to severe COPD patients in a 3-arm randomized blinded trial. Patients will receive 26 weeks of infliximab, 24 weeks inflixamab/12 weeks' placebo or 36 weeks of placebo treatment. Our primary outcome will be 6 minute walking distance, a measure of exercise tolerance. A number of secondary variables including proinflammatory cytokines in sputum and blood, pulmonary physiological and metabolic outcomes, body composition and quality of life (QOL) indices will be measured as well. The second proposal is on the use of inhaled steroids in COPD. Results from previous trials have in general been disappointing. However, there are likely to be subsets of patients who respond. We predict that patients with a prominent airway inflammatory component to their disease will be likely to respond to inhaled steroids and would be candidates for long-term treatment. We will determine if the sputum level of proinflamamtory cytokines is predictive of the response to steroid inhalers in COPD. We will determine if the presence of a single nucleotide substitution in the glucocorticoid receptor has a negative impact on the response. Outcomes from this randomized clinical trial will be gauged in terms of health related QOL. In addition to presenting these formal proposals, we have developed several concept proposals. We have also offered the development of a health cost utilization core for the COPD CRN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CNS ESTROGEN RECEPTORS AND SOCIAL BEHAVIOR Principal Investigator & Institution: Cushing, Bruce S. Associate Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Recombinant adeno-associated viral (rAAV) vectors can be used to directly introduce genes into cells making local manipulation of receptors possible and site-specifically alter the sensitivity of an animal to hormones. The goal of this study is to use this developing technology to enhance ERalpha in male prairie voles (Microtus ochrogaster). E influences a variety of male and female behaviors, including aggression, affiliation, social preferences, parental behavior, and mating. Prairie voles provide a unique opportunity to use rAAV to understand the role of steroids in regulating social behavior. Foremost, prairie voles are highly social and monogamous, displaying many social interactions similar to humans, making them a better rodent model for studying social behavior than species such as rats and mice. The development of ER knockout (KO) mice (a and a) has provided significant insight into the actions of E and with the advent of rAAV ER can be replaced in specific areas providing a powerful tool for examining the effects of E. A disadvantage of ERKO mice is they not only lack ER as adults, but also are not exposed to the organizational effects of E during development. In contrast prairie voles are subject to the developmental effects of E, but at the same time, males, at least from Illinois, express little or no ERalpha, and significantly less than females, in the BST and the MeA. In rats and mice, where
Studies 25
male/female social interactions are often limited to mating, both males and females express high levels of ERalpha in the MeA and BST. The MeA and BST play a major role in regulating social behavior, and a comparison of the pattern found in prairie voles with rats and mice suggests that the lack of ERalpha in these areas could account for increased social behavior displayed by male prairie voles. This possibility is further supported by comparing social behavior and ERalpha between prairie voles from Illinois (IL), which are monogamous, and Kansas (KN), which are less social and show many polygynous characteristics. KN males display an ERalpha pattern intermediate to IL prairie voles and rats, with KN males expressing significantly more ERalpha in the BST and the MA than IL males, but less than KN females in the BST. IL male prairie voles will be transfected with rAAV-ERalpha in the BST and MeA and transfected, sham and control males will be tested for aggression, parental behavior, partner preference, social contact (same and opposite sex), and sexual behavior, with the prediction being that increasing ERalpha will decrease affiliation and increase aggression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITION, STEROIDS AND IMAGING IN CUSHINGS DISEASE Principal Investigator & Institution: Starkman, Monica N. Associate Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 27-SEP-1997; Project End 31-AUG-2004 Summary: (Adapted from applicant's abstract): Dysregulation of the hypothalamicpituitary-adrenal axis resulting in hypercortisolemia is present in a significant proportion of the aged and in neuropsychiatric conditions such as Alzheimer's Disease and Major Depressive Disorder. However, the relationship of this dysregulation to clinical symptoms is still insufficiently understood. Patients with CD exhibit hypercortisolemia and develop disturbances in mood, sleep, libido, and cognition. The investigator's hypothesis is that steroid elevations in these various conditions have important neuroactive effects. The investigator's objective is to examine the role of steroids in the pathophysiology of behavior by exploiting the fact that patients with CD are a unique model providing sustained exposure to high concentrations of endogenous steroids over a long-term period. The studies proposed focus on abnormalities in cognition. Studies in animals indicate that elevated corticosteroids result in toxicity to the hippocampus. This is one likely mechanism for the manner in which glucocorticoids elicit cognitive dysfunction. The investigator proposes to use MRI of the brain together with neuropsychologic (NP) testing to investigate such a mechanism in humans. Evidence is accumulating that other steroids such as androgens play key roles in modulating neuronal excitability. In many patients with CD, testosterone and dehydroepiandrosterone (DHEA) are also markedly elevated. The investigator's specific aims are to: 1) Study in fine detail cognitive dysfunction in patients with CD using sensitive, specific tests with graded levels of difficulty to probe for subtle as well as easily-elicited abnormalities. 2) Examine, prior to treatment, MRI-determined hippocampal formation (HF) volume in patients with CD, and compare to the volume of age, sex, and education-matched normal controls. The investigator will examine specificity for region by measuring and comparing the volumes of caudate head (CH), frontal lobe and anterior temporal lobe (ATL). 3) Examine associations between severity of hypercortisolemia, NP impairment and HF volume. The volumes of CH, frontal and ATL will be used as comparison regions. 4) Repeat NP testing and MRI one and two years following treatment of CD, in order to determine if changes in cognition and HF volume are reversible. Associations between changes in volume and cognitive test
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scores will be studied. 5) Examine the potential modulatory role of the androgens testosterone and DHEA, co-secreted with cortisol, on tests of attention, learning and memory. Hypercortisolemia occurs with aging and in several important neuropsychiatric diseases. The studies proposed will help advance knowledge about the role of the glucocorticoid cortisol in the mechanisms contributing to cognitive dysfunction in these conditions. The rationale for developing protective drugs such as site-specific glucocorticoid receptor antagonists or excitatory amino acid suppressors would be strengthened. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPARATIVE STUDIES OF VOCAL CONTROL Principal Investigator & Institution: Brenowitz, Eliot A. Professor; Psychology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-APR-1995; Project End 31-MAR-2005 Summary: (Adapted From The Applicant's Abstract): A fundamental feature of nervous systems is that they provide plasticity of structure and function which allows animals to adapt to changes in their environment. We are only beginning to understand the underlying mechanisms, the limitations, and the behavioral consequences, such as learning, of naturally occurring plasticity in the brain. The song control system in the avian brain provides excellent opportunities for addressing such basic issues of behavioral neuroscience. Seasonal changes of environmental factors, such as photoperiod, have a profound effect on birds and most other animals. In songbirds seasonal changes in photoperiod elicit changes in circulating concentrations of gonadal steroid hormones, which in turn cause changes in song behavior and in morphological and physiological attributes of the neuroendocrine system that controls song. The exchange of social cues between individuals enhances the growth of the song system during the breeding season. The goal of this proposal is to use a comparative approach to explore the proximate mechanisms and behavioral functions of seasonal plasticity in the avian song control system. We will determine whether the social enhancement of the seasonal growth of the song nuclei is mediated by auditory stimuli. We will examine whether social stimulation from other birds enhances the growth of the song nuclei by increasing the recruitment and/or survival of newly generated neurons in the adult bird's song system. To test the hypothesis that maintenance of seasonally grown song nuclei depends on innervation from afferent nuclei, we will lesion nucleus HVc unilaterally in canaries that have been on breeding photoperiods for one month and compare the morphology of the afferent nuclei RA and Area X ipsilateral and contralateral to the lesion. The hypothesis that seasonal growth of the song nuclei is regulated by estrogenic metabolites of testosterone will be tested by measuring the morphology of song nuclei, song behavior, and plasma hormone levels in wild song sparrows implanted in early Fall with different steroids. We will use operant conditioning techniques to test the hypothesis that seasonal changes in song perception are functionally related to seasonal plasticity of the song system. The results of the proposed studies will increase our understanding of steroid hormonal and social influences on the nervous system, and of the relationship between plasticity in the adult brain and learning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORTICOTROPIN-RELEASING HORMONE-BINDING PROTEIN Principal Investigator & Institution: Seasholtz, Audrey F. Associate Professor; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-DEC-1990; Project End 30-JUN-2005 Summary: (Scanned from the applicant's abstract) Corticotropin-releasing hormone (CRH) is widely recognized as the key physiological regulator of the mammalian stress response. Within the hypothalamic-pituitary-adrenal (HPA) axis, CR1-I is the principal hypothalamic hormone controlling pituitary ACTH synthesis and release. At other sites in the central nervous system (CNS), CRH is thought to act as a neurotransmitter to mediate the behavioral, autonomic, and immunological responses to stress. The recent characterization of urocortin, a new CR1-I-like ligand in mammals, adds to the complexity of the CRH system. Both CRH and urocortin mediate their endocrine and/or synaptic effects via two classes of CRH receptors. Similarly, both CRH and urocortin bind to the CRH-binding protein (CRH-BP). This secreted binding protein is smaller than the CRH receptors, but binds CRH and urocortin with an affinity equal to or greater than that of the receptors, and blocks CRH-mediated ACTH secretion in vitro. The CRH-BP is expressed in the anterior pituitary and brain of rodents and primates. Some regions of CRH-BP expression colocalize with sites of CRH synthesis or release, suggesting that this binding protein may have a profound impact on the biological activity of CRH as a hypothalamic releasing factor and neurotransmitter. We have hypothesized that the CRH-BP is an important modulator of the actions of CRH and other CRH-like ligands in the pituitary and central nervous system in vivo. Recent studies in our laboratory suggest that gonadal steroids regulate pituitary CRH-BP expression. This sexual dimorphism in CRH-BP expression suggests that the CRH-BP may exhibit new gender-specific modulatory roles in the pituitary and brain. Studies in this proposal will examine the modulatory roles of the CRH-BP by characterizing its regulation in vivo and in vitro and examining its functions in mouse models of altered CRH-BP expression, paying particular attention to sexually dimorphic phenotypes. Studies in Aim I examine the in vivo regulation of pituitary CRH-BP expression by gonadal steroids. In Aim II, the molecular mechanisms mediating steroid hormone regulation of CRH-BP gene regulation will be examined, focusing principally on the differential regulation by glucocorticoids and positive regulation by estrogen. In aims 3 and 4, the in vivo roles of CRH-I-BP will be further analyzed using CRH-BP-deficient mice and new transgenic models of targeted, inducible CRH-BP overexpression. As dysregulation of CR1-I activity is thought to play a significant role in major depression, anxiety disorders, and anorexia nervosa, a clearer understanding of the role of CRH-BP in the modulation of activity of CR1-I and other CRH-like ligands may be important to our understanding of the etiology and treatment of these human disease states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOKINE CASCADE IN BLOOD & CENTRAL NERVOUS SYSTEM Principal Investigator & Institution: Coe, Christopher L. Professor; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVES To examine the influence of cytokines on the release of soluble mediators in the peripheral blood and intrathecal compartments. RESULTS Cytokines, such as interleukin-1 (IL-1), are potent stimulators of endogenous cytokine release and the neuroendocrine axis, and thus play an important role in the communication between
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the immune system and the brain. We have been investigating the influence of IL-1 on other cytokines, such as interleukin-6, in the peripheral blood and intrathecal compartments. Following our demonstration that IL-6 is released endogenously from within the CNS, we have been investigating the primary cellular source. This research has focused on the endothelial cells of the blood-brain-barrier. In addition, we have been investigating the degree to which corticosteroids are involved in modulating these proinflammatory responses, which has bearing on the role of steroids in sepsis and anaphylactic shock. FUTURE DIRECTIONS Our studies are now focused on endothelial cells of the blood-brain-barrier. For this project, we have established endothelial cell cultures that will permit the research to go forward with in vitro models of the BBB. KEY WORDS cytokines, interleukin-1, interleukin-6 cerebrospinal fluid, psychoneuroimmunology FUNDING NIMH Dissertation Award, NSF Predoctoral fellowship, NIMH MH41659 PUBLICATIONS Reyes, T.M. and Coe, C.L. 1998. The proinflammatory cytokine network Interactions in the CNS and blood of rhesus monkeys. American Journal of Physiology 43 R139-149. Reyes, T.M. & Coe, C.L. 1998. Resistance of the central nervous system interleukin-6 to glucocorticoid inhibition in monkeys. American Journal of Physiology 44 R612-618. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINE REGULATION OF BETA PROTEIN DEPOSITION Principal Investigator & Institution: Frautschy, Sally A. Associate Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 29-SEP-1991; Project End 31-MAY-2005 Summary: This continuation begins with three key observations: a) Although limited glia-associated Abeta remains for more than a year, most of the injected or infused betapeptide (Abeta) is rapidly scavenged by microglia/macrophages, a process key for Abeta removal. Abeta deposits are not stable and may be degraded or contribute to soluble Abeta aggregates that are potentially neurotoxic. b) Persistent plaque-like deposits in rats chronically infused with Abeta can be induced by an initial co- injection (i.e. transient presentation) of the potent anti- inflammatory cytokine, TGFbeta1. c) Abeta deposition by itself may not be sufficient to induce the major neurodegeneration found in AD because human and animal models can have large amyloid burdens with no dementia and limited synapse or neuron loss. We hypothesized that inflammatory factors regulate deposition and neurodegeneration and that TGFbeta1's antiinflammatory effect leads to deactivation of microglial phagocytosis of Abeta. We have now shown that TGFbetas1 and 3 also increase microglial associated Abeta (chemotaxis) and extracellular deposits in vivo as well as in an organotypic hippocampal slice culture (OHSC), a useful system for investigating the impact of cytokines on Abeta trafficking, deposition or degradation. We present new data supporting the hypothesis that TGFbetas and other microglial activation immunomodulators regulate Abeta deposition/degradation in vivo using our infusion paradigm. TGFbeta1 and very different antiinflammatory agents including steroids, curcumin and NS-398 (a specific COX II inhibitor) all increased Abeta deposition, but reduced neurotoxicity. In fact, in our Abeta infusion paradigm, increasing Abeta deposition is negatively correlated with Abeta toxicity across a number of very different manipulations consistent with the hypothesis that soluble Abeta or small aggregates available to neurons are more neurotoxic than massed aggregates walled off by glial scar formation. In contrast to TGFbetas1 and 3 brief exposure to TGFbeta2 causes increased region-specific neuronal Abeta immunoreactivity including in the CA1 and
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entorhinal cortex. Because TGFbeta2 is elevated in AD brains, this observation raises the hypothesis that TGFbeta2 increases trafficking of Abeta to neurons and results in neurotoxicity (Aim 1) and compromised neuronal function with reduced hippocampal LTP and spatial memory (Aim 2). The hypothesis that elevated TGFbeta2 expression is a correlate of neurotoxicity is also tested in Aim 3 which characterizes overall cytokine profiles in humans and animal models with and without major Abeta accumulation and neurotoxicity. In Aim 4 we test the hypothesis that acute TGFbeta2 induces persistent antiinflammatory cytokine profiles and characterize the impact of chronically elevated antiinflammatory cytokines on Abeta deposit degradation and neurotoxicity in vitro. Aim 5 pursues these goals in vivo. This project is designed to better understand the role of NSAIDs and antiinflammatory cytokines, especially TGFbeta2 in regulating Abeta deposition, trafficking, degradation and neurotoxicity. It should be of direct relevance to the prevention and treatment of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINE SIGNAL TRANSDUCTION IN OSTEOBLASTIC CELLS Principal Investigator & Institution: Bellido, Teresita M. Research Associate Professor of Medicine; Internal Medicine; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, AR 72205 Timing: Fiscal Year 2001; Project Start 15-DEC-1996; Project End 30-NOV-2001 Summary: Work leading to this application indicates that cells of the stromal/osteoblastic lineage collectively display all the known alpha and Beta subunits of the receptors for the interleukin-6 family of cytokines that includes IL-6, IL-II, LIF, CNTF, and OSM; different representatives of the lineage, however, express different receptor repertoire. Furthermore, acting via their specific receptors IL-6 type cytokines increase alkaline phosphatase and inhibit cell growth, suggesting their ability to induce differentiation. In addition, the level of expression of both the alpha and Beta subunits of these receptors is modulated in vitro by systemic hormones, such as sex steroids, parathyroid hormone and Vitamin D3. Based on these lines of evidence, the following hypotheses will be tested: IL-6 type cytokines act on cells of the osteoblastic lineage to promote their differentiation. Different members of the group act at specific stages of the differentiation process and such stage- dependent responsiveness to a particular cytokine is achieved by expression or repression of the respective receptor. Systemic hormones and other locally produced growth factors influence the prodifferentiating effects of these cytokines by modulating the level of cytokine receptor expression. To test these interrelated hypotheses, the specific aims of this application are to determine the effects of IL-6, IL-II, LIF, CNTF, and OSM on the expression of collagen type I, alkaline phosphatase and osteocalcin, osteoblast phenotype-related genes representative of proliferation, maturation and mineralization, respectively. In these experiments established osteoblast-like cell lines from animals and humans as well as primary cultures of murine calvaria cells and Northern blot analysis will be employed. Further, the effects of sex steroids, PTH, 1,25(OH)2D3, glucocorticoids, and retinoids on the expression of the ligand-binding subunit of IL-II and CNTF, and LIFRBeta and OSMRBeta, in the above cell models will be determined: and whether these changes alter cellular responsiveness to these cytokines. Finally, the pattern of distribution of cytokine receptors will be determined in cells of the osteoblastic lineage in vivo; from immature osteoblast precursors of the marrow, to the earliest morphologically recognizable elliptical preosteoblasts (type I cells) to cuboidal mature osteoblasts (type II cells) to older flattened and more elongated lining cells (types III and IV cells) and osteocytes. These studies will be performed in: a) bone marrow cell aspirates and b)
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sections of bone tissue from mice, and in situ RT-PCR in combination with histostaining and dynamic bone histomorphometry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINES INTERACTIONS
AND
HYPOTHALAMIC-PITUITARY-IMMUNE
Principal Investigator & Institution: Wardlaw, Sharon L. Professor; Medicine; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 10-MAR-1998; Project End 30-NOV-2002 Summary: (Adapted from the Applicant's Abstract): The long-term objective of this application is to understand how the immune and neuroendocrine systems interact when activated by stress or infection in the human and nonhuman primate. The specific aims will focus on the inflammatory cytokines (IL-1, IL-6, TNFalpha) and mechanisms of hypothalamic-pituitary-adrenal (HPA) activation with an emphasis in the role of gonadal steroids in modulating cytokine and neuroendocrine responses. Previous studies in the investigators' laboratory have established that intracerebroventricular (icv) IL-1 stimulates the HPA axis in the monkey and that this affect can be blocked by corticotropin-releasing hormone (CRH) antagonism. Preliminary studies in the monkey indicate that icv IL-1 also causes profound suppression of lymphocyte function and marked stimulation of Il-6 secretion into peripheral blood, possibly by a CRH dependent mechanism. In this application, using rhesus monkeys, IL-1 CRH interactions in the brain and their modulation by gonadal steroids will be examined in vivo with respect to mechanisms of HPA activation and regulation of peripheral lymphocyte and cytokine responses. A major focus will be to characterize the endogenous cytokine and neuroendocrine responses caused by a physiological inflammatory challenge in the human. Low doses of a highly purified endotoxin preparation will be use to stimulate cytokine release and to characterize the HPA response in women in the presence and absence of gonadal steroids. The CNS cytokines and CRH into CSF after stimulation with endotoxin will be measured in monkeys with chronic CSF catheters, and specific cytokine antagonists will be infused icv to establish a role for the endogenous cytokines within the brain in neuroendocrine regulation. The ability of gonadal steroids to modulate central cytokine release will also be studied. These studies may relate to a wide range of human diseases since cytokine interactions in brain triggered by injury or infection may be associated with neurodegeneration and immunosuppression. If sex steroids restrain these cytokine-neuropeptide interactions, such pathology could be exacerbated when sex steroid levels fall. These studies should thus have direct relevance to the important clinical issue of sex steroid replacement during menopause and in other hypogonadal states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF POTENT YET SAFER ANTI-INFLAMMATORY AGENTS: VIA MUTUAL PRODRUG APPR Principal Investigator & Institution: Mclean, Hugh M.; Hampton University E Queen & Tyler Sts Hampton, VA 23668 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Chronic inflammatory diseases affect approximately 10% of the U.S. population. Although both anti-inflammatory steroids (glucocorticoids) and non-steroidal antiinflammatory drugs (NSAIDS) are routinely used to provide palliative therapy for many of these maladies, there is still a distinct paucity of "safe"
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and effective drugs, particularly for long term therapy of many inflammatory diseases such as asthma, psoriasis, ulcerative colitis and rheumatoid arthritis. Glucocorticoids are usually considered to be the drugs par excellence for relieving inflammatory symptoms, however their therapeutic use is restricted due to their propensity to elicit potentially serious adverse effects, particularly their suppressive effects on pituitary function and the immune system. The main thrust of the proposed study is the development of antiinflammatory steroids with diminished penchant to elicit untoward systemic effects, via the mutual prodrug approach. To this end, the primary strategy is to incorporate a metabolically labile moiety, a carboxylic acid ester, into the steroid molecule (prednisolone), which would undergo facile systemic biotransformation to the less active and more readily excretable steroidal carboxylic acid. Such steroid acid esters have been dubbed antedrugs. To further enhance the topical potency and local/systemic activity ratios of these antedrugs, they will be conjugated via an ester linkage to selected NSAIDS (such as ibuprofen and indomethacin) at the 21-position of the glucocorticoids. Conjugates such as these have been dubbed mutual prodrugs, primarily because it is conceivable that upon administration, they would be biotransformed into the glucocorticoid and the NSAID, both of which could conceivably exhibit synergistic antiinflammatory activity. The results of these studies should establish axiomatically if the conjugation of glucocorticoids that are "antedrugs", and NSAIDS, is a fundamentally sound synthetic ploy in the development of potent yet safer anti-inflammatory steroids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIETARY ZINC--ITS EFFECTS ON THE IMMUNE RESPONSE Principal Investigator & Institution: Fraker, Pamela J. Professor; Biochem and Molecular Biology; Michigan State University 301 Administration Bldg East Lansing, MI 48824 Timing: Fiscal Year 2001; Project Start 01-JUN-1996; Project End 30-JUN-2003 Summary: Key to this project is the identification of the underlying mechanisms that cause the lymphopenia and reduced host defense that accompanies zinc deficiency (ZD) in humans and animal. The hypothesis to be tested is that ZD heightens apoptosis, reduces cycling and rate of production of precursor lymphocytes in the marrow and thymus. Conversely, the first line of defense, the phagocytic or myeloid cells, appear to be afforded some protection against ZD perhaps to provide minimal immune defense. Using the young adult mouse the following will be our objectives. 1. Lymphopoiesis: The effects of ZD over time on the phenotypic distribution, cell cycle status and rate of production and replenishment of precursor cells in the marrow will be assessed. 2. Myelopoiesis - Hematopoiesis: The impact of ZD on the stem cell, progenitor, erythroid and myeloid compartments will be monitored and the effect (if any) of ZD on myelopoiesis determined. Because there is a significant increase in neutrophils in the blood of ZD mice, it will be important to determine if they retain their phagocytic and killing capacity and if their half-life is altered. 3. Role of Apoptosis: Experiments will be extended that indicate apoptosis is significantly increased among thymocytes from ZD mice. The glucocorticoid antagonist RU38486 will be implanted to reduce the impact of the steroids produced during ZD to potentially open the way for drug and/or cytokine therapy in malnourished subjects. 4. Zinc - Induced Apoptosis: Finally, it will be shown that physiologically relevant levels of zinc (nM) can induce apoptosis in precursor cells being a new role for zinc. Human leukocytes, testicular cells, kidney cells, hepatocytes, etc., will be tested for propensity to undergo zinc-induced death. Whether the zinc death cascade includes classical components such as cell condensation, lipid inversion, activation of caspases, DNA fragmentation and induction of death genes will be determined. Transgenic mice over-expressing bcl-2 in their B-cell compartment will be
32 Steroids
used to determine if this important protooncogene acts as a regulatory point for the Zndeath pathway. Collectively, these experiments will provide the first detailed picture of the effect of a nutritional deficiency on the composition, function and regulation of the marrow and the role Zn can play in modulation of apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFERENTIAL EFFECTS OF GONADAL STEROIDS ON BONE Principal Investigator & Institution: Leder, Benjamin Z.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Osteoporosis in men is an important cause of morbidity and mortality, especially in the elderly. Hypogonadism is a well described risk factor for osteoporosis in men, but the mechanisms underlying hypogonadism-induced bone loss are incompletely understood. A fundamental unresolved question in this area concerns the differential effects of androgens and estrogens on the male skeleton. To address this question, in the first of 3 proposed studies, normal men will be randomly assigned to receive: 1) a GnRH analog alone for 12 weeks (suppressing endogenous gonadal steroids to pre-pubertal levels), 2) a GnRH analog plus testosterone (T) (normalizing circulating T and estradiol levels), or 3) a GnRH analog plus T plus an aromatase inhibitor (normalizing T but causing selective estrogen deficiency). Bone turnover markers will be measured every 4 weeks. Bone turnover will increase in Group 1 and should remain unchanged in Group 2. If estrogens are required to maintain normal bone turnover in men, bone turnover should also increase in Group 3. In the second study, normal men will be randomized into similar treatment groups for 8 weeks with the addition of a group that will receive a GnRH analog plus physiologic estradiol. PTH infusions will be performed every 4 weeks and bone turnover markers will be measured every 6 hours during each infusion. By comparing the rates of change in these markers during PTH infusion, the selective effects of androgens and estrogens on the skeletal sensitivity to PTH will be assessed. In the third protocol, murine stromal cell lines and primary mouse osteoblasts will be exposed to estrogens and androgens to assess their differential effects on osteoprotegerin (OPG) and osteoprotegerin-ligand (OPG-L) mRNA expression. These studies will help elucidate the mechanisms by which gonadal steroids act on bone and enable the candidate to appreciate basic developments in bone biology as well as develop and perform future translational research projects. The training portion of the proposal includes regular mentoring with Drs. Finkelstein and Bringhurst, extensive interaction with the Endocrine Unit faculty, and meetings with the GCRC biostatistician. The candidate will also enroll in the Harvard School of Public Health's Clinical Effectiveness Program and participate in courses offered by the MGH Clinical Research Program. These combined research and didactic endeavors will prepare the candidate to achieve his long-term goal to develop an independent research program focusing on the role of gonadal steroids in bone metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISCRIMINATIVE EFFECTS OF BENZODIAZEPINE WITHDRAWAL Principal Investigator & Institution: France, Charles P. Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2002; Project Start 15-MAR-1995; Project End 31-JAN-2007 Summary: Benzodiazepines and related gamma-amino butyric acid (GABA)A modulators are used widely for their anxiolytic, hypnotic and anti- convulsant effects.
Studies 33
These same compounds are also abused, both alone and in combination with other classes of drugs (e.g., opioids), and long- term use of benzodiazepines can lead to clinically significant physical dependence. The GABAA receptor complex is the site of action of other drugs of abuse (e.g., ethanol) and GABAergic systems, in general, are thought to indirectly modulate the effects of still other drugs of abuse (e.g., cocaine). Much has been learned over the past 10 years from molecular studies on GABA receptors, yet little of this knowledge has been applied to studies in behaving organisms, particularly with regard to GABA neurobiology and substance abuse. Procedures have been developed under this grant for studying discriminative stimulus effects of GABAA modulators in rhesus monkeys and studies proposed in this application will use those procedures to investigate the neurobiology of drugs that vary in their actions on GABAergic systems. Studies under Aim 1ill will compare GABAergic and other drugs for their ability to prevent and reverse benzodiazepine withdrawal and also to mimic the subjective (discriminative) effects of benzodiazepine in normal subjects. A parallel study (Aim II) will establish a discrimination with flumazenil in monkeys treated daily with the a1-s3lective positive modulator zolpidem to test whether this widely-prescribed sedative/hypnotic produces dependence that can be differentiated from that produced by diazepam.Neuroactive steroids will be studied under Aim III to see whether th eye modify the behavioral effects of other compounds that act at the GABAA receptor complex. This study is founded on positive preliminary data with pregnanolone and a literature showing that neuroactive steroids uncouple benzodiazepine receptors from the GABAA receptor complex in vitro. Blind evaluation of compounds will continue the auspices of the Drug Evaluation Committee of the College on Drug Dependence under Aim IV. Collectively, these studies will provide important quantitative information on the nature of drug/receptor and drug/drug interactions for GABAA modulators and related drugs. These data will promote an understanding of GABAergic neurotransmission and abuse liability for a variety of clinically relevant compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOES NEBULIZED DEXAMETHASONE IMPROVE PULMONARY FUNCTION IN NEONATES? Principal Investigator & Institution: Lugo, Ralph A.; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001 Summary: The specific aims of this randomized, double-blinded, placebo-controlled study are to: 1) measure the relative systemic availability of inhaled dexamethasone and assess the consistency of systemic absorption during a course of inhaled dexamethasone; 2) evaluate and compare changes in ventilatory support (rate of ventilation), peak inspiratory pressure, and fractional inspired oxygen in ventilator-dependent premature neonates receiving a 7-day course of inhaled dexamethasone or intravenous dexamethasone and; 3) define relationships between systemic drug exposure and improvements in ventilatory parameters and adverse effects after both intravenous and inhaled dexamethasone. Twenty patients have been enrolled on this study, but results have not yet been analyzed. An important treatment objective is to determine if one or the other forms of therapy being evaluated will reduce the severity and complications of bronchopulmonary dysplasia by minimizing ventilator-induced barotrauma and oxygen toxicity. Previous studies suggesting benefit from intravenous dexamethasone infusions were not blinded, and thus management may not have been equal between treated and untreated groups. Despite the apparent advantage of aerosolized steroids in minimizing
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systemic steroid exposure, studies conducted in neonates have not compared efficacy, adverse effects, or systemic absorption of inhaled steroids, and compared the outcome to more commonly administered intravenous dexamethasone. If inhaled steroids result in improved pulmonary function comparable to that claimed for intravenous steroids, the risk-benefit ratio would clearly favor treatment by inhalation. This protocol will address this very important issue in the care of premature neonates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF OXANDROLONE ON EXERCISE AND LV FUNCTION IN CHF Principal Investigator & Institution: Ansari, Maria N. Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-2001 Summary: Chronic heart failure (CHF) is a leading cause of morbidity and mortality. Exercise intolerance is a major limiting symptom in CHF and is due, in part to abnormalities of skeletal muscle. Reduced exercise capacity and degree of cachexia are associated with a poor prognosis. Anabolic steroids have increased lean body mass and improved muscle function in a number of wasting syndromes, but have not been studied in CHF. Specific Aims: To test the hypotheses that oxandrolone, an anabolic steroid with minimal androgenic effects, will: 1) increased skeletal muscles size and function and improve exercise capacity; 2) increase left ventricular (LV) mass and improve cardiac function in CHF patients. Methods: This will be a randomized, doubled-blind, placebo-controlled pilot study of 48 patients with ejection fractions (EF) 7.5% of the previous weight over 6 months). Patients will be randomized to oxandrolone 10mg po bid or placebo in a 2:1 ratio. The following measurements will be made at baseline and after 4 months of treatment: 1) lean body mass by dual-energy-xrayabsorptiometery; 2) strength and endurance of the quadriceps muscle by isokinetic dynamometry; 3) exercise capacity by respiratory gas exchange; 4) LV mass and EF by cardiac MRI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF RALOXIFENE ON SALIVARY STEROIDS Principal Investigator & Institution: Jordan, V. Craig. Cancer Center; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 02-MAR-2001; Project End 28-FEB-2003 Summary: (Applicant's Description) Raloxifene, a chemical cousin of tamoxifen, is currently being tested as a breast cancer preventive in Study of Tamoxifen and Raloxifene (STAR) in postmenopausal, high-risk women. Raloxifene is a drug approved to prevent osteoporosis and has not been tested in premenopausal women. Clearly, if raloxifene is found to be of value to prevent breast cancer in postmenopausal women there will be a need to use the drug in premenopausal women. The NCI has initiated a safety study to evaluate the effect of raloxifene on bone density in high-risk premenopausal women. Raloxifene is a less estrogenic antiestrogen than tamoxifen and there is a possibility there could be significant bone loss. Additionally, it is anticipated that raloxifene will have an effect on the menstrual cycle. This is being monitored by extensive blood drawings. However, this is extremely inconvenient for any clinical study. This proposal monitors the actions of raloxifene on circulating steroids by measuring estradiol and progesterone in saliva. We have developed and validated a sensitive assay to measure salivary steroids. The clinical work is ongoing and the
Studies 35
specific aims are 1.) to determine the salivary changes in estradiol and progesterone throughout the menstrual cycle, 2.) to establish the changes initiated by two doses (60mg and 300 mg daily) of raloxifene by comparison with nontreatment cycles, and 3.) to determine changes in salivary cortisol produced by raloxifene. Completion of the safety study will establish the endocrine effects of raloxifene in pre-menopausal women. Most importantly, completion of the study will validate an important new methodology to monitor the ovarian effects of any new chemopreventive that can be used in premenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF ANDROGENS, ESTROGENS, AND PTH ON BONE Principal Investigator & Institution: Finkelstein, Joel S. Massachusetts General Hospital 55 Fruit St Boston, MA 02114
Associate
Professor;
Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-JUL-2004 Summary: The goal of this application is to support my personal development as a clinical investigator and to help me train future clinical investigators. My clinical research program has two global aims. The first global aim is to investigate the anabolic actions of parathyroid hormone (PTH) on the skeleton, particularly as an agent to prevent estrogen deficiency bone loss. There are 2 major projects to address this aim: 1) an investigation of the effects of ability of short-term parathyroid hormone administration on bone loss in young women with GnRH analog-induced estrogen deficiency and 2) an investigation of the effects of ability of long-term parathyroid hormone administration to prevent bone loss in early postmenopausal women. The first of these projects was supported by an NIH FIRST Award that expires next year. This project demonstrated that daily PTH administration prevents bone loss from the spine, hip, and total body when a GnRH analog is administered to young women for 1 year. This study was too short, however, to determine whether PTH could prevent cortical bone loss in estrogen- deficient women but it did provide the basic premise for the second project which is funded as a portion of the MGH Specialized Center of Research (SCOR) grant on osteoporosis. The second global aim of my research program is to assess the roles of androgens and estrogens on the skeleton. This aim encompasses 2 additional projects: 1) The Study of Women's Health Across the Nation (SWAN) and 2) a group of newly designed studies to investigate several key questions about the roles of androgens and estrogens in bone metabolism in men. SWAN is a multicenter, multiethnic study investigating a wide range of physiologic, endocrinologic, epidemiologic, and psychosocial issues as women transition through the menopause. One key aim of SWAN, which is the major reason for my participation, is to assess the relationship between estrogen deficiency and bone loss during the menopause transition. The newly designed studies on androgens and bone will examine the relative roles of androgens and estrogens in maintaining bone turnover in men, the dose-response relationship between gonadal steroids and bone turnover in men, and novel ways to prevent androgen-deficiency bone loss in men. If I am successful in obtaining this award, I will be able to reduce my current clinical activities by 50 percent and devote the additional time to my clinical research studies. Moreover, I am now training a clinical research fellow in endocrinology and a junior staff member of the Department of Medicine, both of whom are interested in the roles of androgens on the skeleton. It is clearly necessary for me to reduce my current clinical activities in order to devote sufficient time to the training of these young clinical investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF INHALED STEROIDS ON AIRWAY DISTENSIBILITY Principal Investigator & Institution: Jean, Lee-Gardie; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 25-FEB-2003 Summary: (provided by applicant): Patients with severe asthma have chronic airflow limitation that is partly due to increased airway smooth muscle tone and structural changes of the airway wall. In addition, such patients appear to have lost a major protective function of their lungs, the ability of lung infaltion (through deep inspiration) to reverse airway tone and to bronchodilate. This ability is strong in halthy subjects and only minimally reduced in mild asthmatics. Using HRCT, our group has observed that lung inflation distends the airways of healthy subjects and subjects with mild asthma. However, a decrease in airways distensibility has been observed in subjects with chronic airflow limitation. There are two possible causes for reduced airways distensibility, increased airway tone and/or structural wall changes. These structural wall changes have a reversible and irreversible component. The reversible component is believed to be sensitive to steroids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENVIRONMENTAL INFLUENCES ON BRAIN PLASTICITY Principal Investigator & Institution: Crews, David P. Professor; Zoology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, TX 78712 Timing: Fiscal Year 2001; Project Start 10-MAR-1998; Project End 28-FEB-2003 Summary: (Adapted from applicant's abstract): This research addresses the fundamental question of what determines behavioral variation. Many environmental variables can produce predictable effects on phenotype. One such variable is the incubation temperature of eggs in many reptiles. In the leopard gecko, embryos become male or female depending upon their temperature during development. In addition, betweensex as well as within-sex differences attributable to incubation temperature have been found in morphology, secretion of and sensitivity to steroid hormones, sociosexual behavior, reproductive success, and in the neuroanatomy and metabolic activity of brain areas that mediate sociosexual behaviors. These environmental effects are analogous to the effect of intrauterine environment in mammals, including humans. Given the homology of the endocrine and nervous systems across vertebrates, it is important to determine if homologous mechanisms underlie these analogous effects on behavior. If the mechanism underlying environmental effects on behavior in the leopard gecko is conserved (i.e., via sex steroids), this research will lend new insight into the evolution of sexual differentiation because temperature-dependent sex determination is thought to be the evolutionary precursor to genotypic sex determination (present in birds and mammals) and because reptiles are the ancestors of both birds and mammals. If the mechanism is different (i.e., direct temperature effects), this research would elucidate a novel process of sexual differentiation that may also be present in birds and mammals but, because of homeothermy, is masked. This latter possibility is especially important because young birds and mammals cannot regulate their body temperature as do adults. The proposed research is broadly categorized into three groups: thermoregulation and its relation to sociosexual behaviors (i.e., the degree to which the neural substrates mediating thermoregulatory and sociosexual behavior overlap), the development of the neural phenotypes of these brain regions and hormone milieus, and the effects of hormonal manipulations during development and neural manipulations in adulthood on thermoregulatory and sociosexual behaviors. The final category of experiments is
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particularly important as it will discern whether the incubation temperature effects are direct or indirect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN AND INFLAMMATION IN TMD PAIN Principal Investigator & Institution: Bereiter, David A. Research Professor; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 30-JUN-2007 Summary: (provided by applicant): Arthritis and musculoskeletal disorders, including temporomandibular joint disorders (TMD), are chronic pain conditions that occur more frequently in women of reproductive age than men. Current status of the neural mechanisms of articular pain has relied mainly on experimental models of the knee or ankle joint. However, organizational differences between trigeminal and spinal systems suggest the mechanisms that mediate deep craniofacial pain cannot be fully understood from results obtained by other models of joint pain. The proposed experiments use an animal model to study nociceptive signaling from the temporomandibular joint (TMJ) by neurons in the lower trigeminal brainstem under naive conditions and during chronic inflammation. The overall goal of this study is to test the hypothesis that sex steroid hormones influence central neural processing of sensory signals arising from TMJ region. Aim 1 determines if sex steroid replacement therapy (estrogen and progesterone) modifies neural activity evoked by stimulating the TMJ. Aim 2 determines if sex steroids act through glutamate receptors to modify processing of nociceptive signals from the TMJ. Aim 3 determines if mitogen-activated protein (MAP) kinase, a transduction pathway shared by estrogen and nerve growth factor, contributes to processing of nociceptive signals from the TMJ. Three approaches are used to provide converging lines of evidence: c-fos immunocytochemistry determines neural population responses at single cell resolution, microdialysis determines amino acid transmitter release and electrophysiological recording determines the properties of individual trigeminal neurons that encode sensory input from the TMJ region. This information may lead to a better understanding of how the brain integrates pain-like signals relevant for TMD in women Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ESTROGEN EFFECTS ON AGE RELATED COGNITIVE DECLINE Principal Investigator & Institution: Gallagher, Michela; Professor; Psychology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from applicant's abstract): The long-term objective of this project is to evaluate the role of estrogen in modulating different types of memory and to understand the neural mechanisms underlying cognitive effects produced by estrogen as a function of aging. Ovarian steroids affect the brain throughout the life span and their effects are not limited to the areas primarily involved in reproduction, but also include the areas relevant to memory. Despite evidence that estrogen affects the brain, however, there have been no studies that directly test the effects of estrogen on memory as a function of aging. Our preliminary studies have indicated that ovariectomy (OVX) has a more rapid effect on cognition in older rats than in young. This has led to our main hypothesis that memory systems are more dependent on estrogens in aged rats. The main aims proposed in this application are to test the working hypothesis that with aging or long-term deficiency of estrogen, cognitive functions decline, and therefore,
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become more dependent on estrogens. Furthermore, it can be predicted that the types of memory that decline most with aging are most sensitive to estrogen. These studies will test these hypotheses in extended behavioral analyses that will produce detailed information on the interactions of aging and estrogen effects on cognition and the role of IGF-1 as a possible mediating mechanism for estrogen effects in the brain. The four specific aims that will be tested are whether 1) specific cognitive functions are more sensitive to estrogen, 2) with longer estrogen withdrawal cognition will decline more and effects of estrogen will depend upon the duration of the withdrawal, 3) estrogen effects differ as a function of aging, and 4) IGF-1 effects on NMDA receptors mediate the estrogen induced effects on cognition. The results of these studies will be the first to critically analyze the effects of estrogen on cognition as a function of aging, duration of estrogen deficiency and type of cognitive task and will also, test a potential neuroendocrine mechanism. Therefore, the data will be of importance in the understanding of age related changes in cognitive function and will have important clinical relevance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN, HIPPOCAMPAL NEUROGENESIS AND LEARNING Principal Investigator & Institution: Gould, Elizabeth; Professor; Psychology; Princeton University 4 New South Building Princeton, NJ 085440036 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 05-DEC-2002 Summary: The dentate gyrus of the hippocampus is unusual because it continues to produce new neurons in adulthood in a variety of mammals, ranging from rodents to primates. Exposure to learning tasks that require the hippocampus for acquisition enhances the survival of adult-generated neurons in the dentate gyrus. In addition, adult female rats produce more new neurons than males, and these sex differences are positively correlated with sex differences in hippocampal-dependent learning. These findings indicate that learning influences the survival of new hippocampal neurons and raise the possibility that adult-generated granule neurons are involved in hippocampaldependent learning. The broad, long-term objectives of this proposal are to characterize the influence of ovarian steroids and learning on the production, survival and gene expression of hippocampal granule neurons generated in adulthood in both sexes. Moreover, the potential role that new granule neurons play in hippocampal-dependent learning and memory will be explored. Using associative learning paradigms of trace classical eyeblink conditioning and the Morris spatial water maze, the role of hormones and experience in the production and survival of new granule neurons in males and females will be investigated with markers of proliferating cells, such as 3H-thymidine and bromodeoxyuridine, combined with immunocytochemistry for neuronal and glial markers. Combined in situ hybridization and immunocytochemistry will be used to explore changes in expression of genes important for cell survival, synaptic plasticity and/or learning, such as NMDA receptor subunits, BDNF and bcl-2, specifically in adult-generated granule neurons following associative learning. Furthermore, the function of hippocampal granule neurons generated in adulthood will be explored in animals depleted of new neurons by endocrine manipulations or treatment with selective toxins for proliferating neuronal precursors and then tested on tasks that require the hippocampal region for acquisition. This proposal is relevant to disorders or age- and disease-related cognitive decline which can be ameliorated by ovarian steroids. In addition, these studies may provide insight into mechanisms of neuronal regeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM
ESTROGENIC
STEROIDS--NEUROTROPHIC
ACTION
AND
Principal Investigator & Institution: Brinton, Roberta Diaz. Associate Professor and Director of The; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001 Summary: The broad goal of this research is to discover estrogenic steroids with neurotrophic activity that will promote the growth and survival of neurons derived from brain regions involved in cognitive function. Germination this proposal began when we discovered several estrogenic steroids that exhibit relatively low affinity for the uterine estrogen nuclear receptor (122-126), which could reduce the risk of breast and uterine cancer, but which exerted a neurotrophic effect similar to what we had observed for the endogenous human female estrogen, and beta-estradiol. (3) Of particular interest was the neurotrophic activity of the equine estrogen, equilin. Equilin is a major component of Premarin, a complex formulation of at least 10 different conjugated equine estrogens, that is currently the leading prescribed pharmaceutical for estrogen replacement therapy in postmenopausal women and is currently under study in 8,000 women participating in the multicenter Women's Health Initiative Memory Study. (59) The proposed studies are designed to test the overall hypothesis that steroids which are estrogenic in chemical structure will influence neuronal outgrowth and survival with varying efficacies depending on their molecular structure. Further, the basis for the different efficacies and potencies of estrogen steroids on neuronal outgrowth will be reflected in their ability to regulate receptor channel function. We further hypothesize that mechanisms that promote an increase in intracellular calcium will underlie estrogenic steroid-induced neurotropism. Lastly, we hypothesize that estrogenic steroids that exert a neurotrophic effect will also promote neuronal survival by enhancing viability and thereby will enhance the capacity of neurons to resist a oxidative stress by beta-amyloid peptide and other free radical generators. To test these hypotheses morphological analyses of dissociated cortical and hippocampal neurons in culture in response to estrogenic steroids and to pharmacological agents that block nuclear estrogen receptors, plasma membrane glutamatergic receptors and protein kinases will be conducted. In addition, whole cell recording will conducted in cultured neurons and slice preparations to analyze the electrophysiological effects of neurotrophic estrogens. Results of these studies will have a direct impact on the use and design of estrogen replacement therapy for the amelioration of cognitive deficits in postmenopausal women and for the prevention of Alzheimer's Disease in this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL WITHDRAWAL AND NEUROACTIVE STEROIDS Principal Investigator & Institution: Finn, Deborah A. Associate Professor; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001 Summary: The neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20 one (3alpha, 5alpha-P or allopregnanolone) is a potent positive modulator of GABA receptors. Recent results from years 01-04 of the previous Center application suggest that genotypic differences in the modulatory effect of 3alpha,5alpha-P on EtOH withdrawal severity may reflect a balance between the change in sensitivity of the GABAa receptors to 3alpha, 5alpha-P that are occurring concomitantly during EtOH withdrawal. These
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studies were conducted in two different animal models of ethanol (EtOH) withdrawal severity [i.e., DBA/2 (D2) and C57BL/6(B6) inbred strains and the selectively bred Withdrawal Seizure-Prone and-Resistant lines]. In addition, gene mapping studies in BXD Recombinant Inbred strains found a significant genetic correlation between chronic EtOH withdrawal severity and a region of chromosome 13 (combined p=0.00008) in which the murine gene for the enzyme 5alpha-reductase-1 (Srd5alpha1). Since 5alphareductase is the rate-limiting enzyme in the biosynthesis of 3alpha, 5alpha-P, we hypothesize that Srd5a1 represents a candidate gene for differences in EtOH withdrawal severity in mice derived form the B6 and D2 inbred strains. Because male and female mice differ in endogenous levels of 3alpha, 5alpha-P (i.e., female > male) and in EtOH withdrawal severity ( female <male), studies related to Specific Aims 1 and 2 will determine whether male and female B6 and D2 mice differ in Srd5a1 sequence and whether the genotypes differ in enzyme activity and/or gene expression of Srd5a1 following exposure to chronic EtOH. The physiological consequence of 5alpha-reductase inhibition or deletion on EtOH withdrawal severity will be examined in Specific Aims 3 and 4. Therefore, the combined use of behavioral, biochemical, genetic and molecular strategies will determine the importance of 3alpha, 5alpha-P as a neuromodulator of EtOH withdrawal severity by assessing Srd5a1 as a candidate gene for genetic differences in EtOH withdrawal severity. These goals are consistent with the two main themes of the Center, which are to identify genes and to explore mechanisms underlying EtOH neuroadaptation. A longer-term goal of this research is to gain information that would help in the development of new strategies for the treatment of alcohol dependence. As recent findings emphasize the therapeutic potential of neurosteroid treatment during alcohol withdrawal, the studies proposed in Component #5 will determine whether neurosteroid biosynthesis represents a target for therapeutic intervention in the treatment of alcohol dependence and withdrawal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXERCISE SUBSTRATE UTILIZATION: THE CROSSOVER CONCEPT Principal Investigator & Institution: Brooks, George A. Professor; Integrative Biology; University of California Berkeley Berkeley, CA 94720 Timing: Fiscal Year 2002; Project Start 15-JUL-1994; Project End 30-JUN-2007 Summary: (provided by applicant): Our overall objective is to identify and understand the factors that control the balance of energy derived from endogenous carbohydrate, lipid, and amino acid sources during sustained, submaximal exercise. A related objective is to understand how various life situations (physical fitness, diet, gender, age) affect the balance of substrate utilization (partitioning) in humans. The theoretical basis of our approach is the 'Crossover Concept' which postulates that during rest and mild to moderate intensity exercise in the post-absorptive state, lipids provide the greatest proportion of energy for muscle and the body at large. However, as the exercise intensity increases from moderate to hard to maximal, the balance of substrate utilization in working muscle switches, or 'crosses over' from lipid to carbohydrate. Using this concept, we seek to describe the mechanisms by which exercise, exercise training, ovarian steroids, age, and dietary history affect the balance of substrate utilization. In pursuit of our overall objective, we propose to explore two specific aims. These are to: (1) describe the interactive effects of exercise intensity and endurance training on muscle and whole body fatty acid oxidation; and (2) evaluate the effects of aging and ovarian sex steroids on the balance of substrate utilization. With these data we shall be able to expand our model of substrate utilization. To assess effects of exercise intensity and to make comparisons at given relative and absolute exercise
Studies 41
intensities before and after endurance training, for Aim 1 young men will be studied before training at power outputs (P0) that elicit 45 and 65% VO2peak; after training they will be studied at the P0 that elicited 65%V02peak before training, and at the new 65%V02 peak. To assess acute and long-term metabolic and enzymatic responses at whole-body and working muscle (leg) levels we will use the combination of tracers {[113C]palmitate, [1,1,2,3,3-2H2]-glycerol (D5-glycerol), and D2-glucose}, indirect calorimetry, (a-v) measurements, biopsies, and, possibly, NMR spectroscopy. For Aim 2 studies on older men, young amenorrhic as well as older postmenopausal women we will use tracers {[1-13C]palmitate, D5-glycerol, D2- and [1-13C]glucose, as well as [113C]leucine}, and indirect calorimetry. On older women longitudinal designs will be employed to assess effects of training and HRT on substrate partitioning. Age-matched males will also be studied. All techniques, whether they involve exercise physiology, indirect calorimetry, tracer infusion and blood sampling, metabolite derivatization, isotopic enrichment determination by GC /MS, metabolite and hormone assays, Western blotting and dietary control, are highly developed by the investigative team. Further, we have the auxiliary personnel and facilities to conduct longitudinal training studies Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FASEB CONFERENCE : STEROIDS AND BONE Principal Investigator & Institution: Kumar, Rajiv M. Chair, Mayo Proteomics Research Center; Federation of Amer Soc for Exper Bio Bethesda, MD 208143998 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2002 Summary: (adapted from the application) This is an application for partial funding of the 2001 FASEB summer conference on "STEROIDS AND BONE" to be held in June, 2001 at the Big Mountain Resort in Whitefish, Montana. The conference is held under the auspices of the Federation of American Societies for Experimental Biology (FASEB). The objective of this meeting is to bring together leading investigators in the area of steroid hormone action and bone physiology, and young investigators (graduate students, postdoctoral fellows, and junior faculty) to discuss innovative ideas and research in an informal setting that is conducive to scientific interchange. The Specific Aims of this conference are: 1) To foster scientific interchange between leading investigators in the area of bone biology and steroid hormone physiology and pharmacology, in an informal atmosphere that encourages the presentation of new information and ideas. 2) To provide the opportunity to young investigators, just beginning their research and scientific careers, to present their scientific data before an audience of established investigators and before their peers. Specific efforts will be made to encourage the participation of women and investigators from under represented minorities. The topics to be included for discussion are: Steroid Hormone Structure and Function, the Role of Co-activators and Co-repressors in Steroid Hormone Function, Estrogen and Progesterone Actions in Bone, Novel Aspects of Steroid Hormone Receptor Signaling, Selective Estrogen Receptor Modulators, Androgen Action /Tissue Selective Androgens, Glucocorticoid Hormones, Vitamin D and Analogs/Mechanisms of Action (2 sessions) and Poster Sessions (4 sessions). There will be nine oral sessions, each including, on average four talks. The first talk will be a "long talk" of approximately 40 minutes duration. Three "short talks" of 20 minutes duration will also be scheduled in each oral session. There will be four poster sessions. Six "free communication" sessions will also be held. Ample time for discussion will be provided. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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•
Project Title: FEMALE GENDER HYPERTENSION
&
EXPRESSION
OF
RISK
GENES
IN
Principal Investigator & Institution: Seely, Ellen W. Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-FEB-1996; Project End 31-JAN-2006 Summary: (Adapted from the applicant's abstract) Hypertension is a major contributor to cardiovascular disease, the leading cause of death in US women. Most studies of hypertension have focused on men. Women have a lower incidence of hypertension until age 50 at which time, the incidence of hypertension in women becomes greater than that in men. Since age 50 is the average age of menopause in US women, this observation suggests that ovarian steroids, present in the premenopausal state, mask genetic predisposition to hypertension and that with loss of these steroids at menopause, genetic predisposition to hypertension becomes manifest. Earlier studies by these workers have shown that a specific intermediate phenotype of essential hypertension is associated with polymorphism of the angiotensinogen gene which result in greater tissue activity of the renin-angiotensin- aldosterone system (RAAS) as a possible cause of hypertension. This phenotype is uncommon in premenopausal Caucasian women compared to age-matched men but the frequency of this phenotype increased at menopause becoming equal in men and women. Estradiol has major effects on many of the genes of the RAAS and therefore is a prime candidate for modulating the expression of genotype and being responsible for the change in phenotype frequency in pre- versus postmenopausal women. The overall objectives of this proposal are to: 1) demonstrate a difference in frequency of specific polymorphism of genes of the RAAS in premenopausal hypertensive women as compare to hypertensive postmenopausal women and men, 2) test the hypothesis that the administration of estrasiol to postmenopausal hypertensive women with these specific polymorphism in RAAS genes will alter the intermediate phenotype and lower blood pressure, and 3) examine activity of the tissue RAAS according to specific genotypes in these three groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FEMALE SEXUALITY: MODULATION BY ESTROGEN AND ANDROGEN Principal Investigator & Institution: Wallen, Kim; Dobbs Professor of Psychology and Behavi; Psychology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The hypothesis is investigated that female sexual interest is stimulated by the neural actions of ovarian estrogens and that androgens regulate the bioavailability of these estrogens through interactions with sex hormone binding globulin (SHBG). Three projects, using a rhesus monkey model of endocrine function and behavior, investigate the hormonal basis of female sexual initiation. Project I investigates sexual initiation in females across the menstrual cycle, comparing the occurrence of female sexual initiation in a social group context during normal cycles treated with an androgen receptor blocker (flutamide) or an estrogen receptor blocker (tamoxifen). This will clarify whether androgens or estrogens act neurally to modulate female sexual motivation. Project II tests the novel hypothesis that SHBG regulates bioavailable estrogens and androgens through these steroids' different affinities for SHBG. This project uses a monkey model of hormonal replacement therapy for reproductively prime females after surgical removal of their ovaries and tests the
Studies 43
hypothesis that chronic estradiol (E2) ceases to effectively stimulate female sexual interest as estrogen is sequestered by SHBG. It further investigates whether an androgen, 5a-dihydrotestosterone (DHT), with a markedly higher affinity for SHBG than estradiol can acutely and rapidly reinstate female sexual interest by increasing free estradiol by displacing SHBG-bound estradiol. Ovariectomized females receiving chronic estradiol treatment mimicking mid-follicular estradiol levels will be observed for sexual initiation during chronic E2 treatment alone and following chronic E2 and an injection of DHT or E2. Concurrent administration of flutamide or tamoxifen with the estrogen or DHT will discriminate between behavioral changes resulting from the activation of neural androgen or estrogen receptors. The effects of these treatments on neuroendocrine function will also be investigated. Project III investigates whether common human hormonal replacement therapies of chronic estrogen, or chronic estrogen plus testosterone with or without concurrent progestin, can reinstate female sexual interest in reproductively prime ovariectomized female monkeys. The hypothesis will be tested that chronic progestin therapy reduces or eliminates the effectiveness of therapies that reinstate female sexual interest without progestin. These therapies will also be compared on their effects on neuroendocrine function. These studies will markedly increase our understanding of the role that ovarian steroids play in modulating women's sexuality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN YOUNG PATIENTS Principal Investigator & Institution: Watkins, Sandra L. Professor of Pediatrics; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, WA 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Primary focal segmental glomerulosclerosis (FSGS) is an organ-specific autoimmune disease with poor response to immunomodulating agents and a poor prognosis. The relatively small number of children and young adults with FSGS and the lack of compelling prospective double-blind randomized multicenter therapeutic studies have hampered the formulation of an evidenced-based therapeutic approach. Cyclophosphamide and calcineurin inhibitors act on different sites of the cytotoxic T cell cycle and support the hypothesis of synergistic effectiveness of combination therapy. We propose a double-blind, randomized, controlled trial comparing A) sequential cyclophosphamide followed by tacrolimus with oral steroids and angiotensin-converting enzyme inhibitors (ACEI) with B) tacrolimus with oral steroids and ACEI. We will develop a database to compare the response to each treatment arm with respect to the primary end-point: reduction in proteinuria. The secondary outcomes will be remission rate, relapse frequency, progression of renal failure as measured by glomerular filtration rate, total cumulative corticosteroid dose and adverse events. Patient age, ethnicity, gender, renal histological classification, podocin mutation status, baseline proteinuria and baseline renal excretory function will be correlated with primary and secondary outcomes. We have formed a Western Pediatric Nephrology Clinical Trials Group consisting of 28 pediatric centers with collaborating adult nephrologists. These centers have a rich history of successful collaborative studies in the past. From our initial survey of patients in the past two years, we have a more than sufficient patient population-base from which to recruit to ensure enrollment of at least 100 study subjects in our region. We will participate as a regional center in the collaborative, multicenter randomized controlled clinical trial of
44 Steroids
therapy to improve the clinical course of children and young adults with primary FSGS as stated in the RFA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GABAERGIC MEDIATION OF STEROID FEEDBACK ON GNRH NEURONS Principal Investigator & Institution: Sullivan, Shannon D. Neurological Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-2002 Summary: Gonadotropin-releasing hormone (GnRH) neurons are the final common pathway regulating reproduction. Pulsatile GnRH release from the hypothalamus stimulates synthesis and secretion of pituitary gonadotropins and is absolutely required for fertility. GnRH pulse patterns are largely regulated by negative feedback from the ovarian steroids estrogen (E) and progesterone (P). Evidence suggests one mechanism of steroid hormone feedback is via interneurons to modulate GnRH pulsatility transsynaptically. Anatomical and physiological data support a role for gammaaminobutyric acid (GABA)-producing neurons in this communication. The goal of this study is to characterize GABA/A-receptor-mediated inhibitory post-synaptic currents (IPSCs) within GnRH neurons and their modulation by steroids and neurosteroids. Specifically, whole-cell voltage clamp techniques will be used to characterize IPSCs in three defined mouse models of steroid hormone feedback. Based on reports of decreased GnRH neuron response to steroid negative feedback in some hypothalamic fertility disorders, IPSCs will also be characterized in an animal model that recapitulates reduced responsiveness to steroid feedback, IPSCs will also be characterized in an animal model that recapitulates reduced responsiveness to steroid feedback. Molecular analyses of GABAA receptor subunit expression within GnRH neurons and changes in hypothalamic levels of enzymes involved in the production of neuroactive steroids will complete these data. The absolute requirement for proper regulation of GnRH pulsatility for fertility underscores the importance of the proposed research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENDER DIFFERENCES IN STIMULANT ACTION Principal Investigator & Institution: Kuhn, Cynthia M. Professor; Pharmacology and Cancer Biology; Duke University Durham, NC 27706 Timing: Fiscal Year 2002; Project Start 15-MAR-1995; Project End 30-JUN-2006 Summary: (provided by applicant): Women comprise about one third of cocaine addicts. They start using cocaine earlier in life, are more sensitive to some cocaine effects and progress to dependence more rapidly. Rodents show some similarities to this pattern: cocaine elicits greater increases in cocaine-stimulated locomotion, females work harder for cocaine reinforcement and extracellular dopamine rises more than in male rats. Our preliminary findings suggest that developmental exposure to gonadal steroids contributes to sex differences in cocaine action. The purpose of this proposal is to investigate the basis for the organizational effect of gonadal steroids on forebrain dopamine systems and the behavioral response to psychomotor stimulants mediated by these systems. We will test the hypothesis that sex differences in cocaine effects reflect anatomical or functional differences in dopamine neurons established during ontogeny. To determine when steroid effects are exerted, male and female rats will be gonadectomized on postnatal day 2, prepubertally on day 25 or in adulthood, and cocaine-stimulated locomotion and electrically-stimulated dopamine overflow will be
Studies 45
determined on postnatal day 70. To evaluate which steroid mediates these effects, rat pups will be treated with vehicle, testosterone or estrogen antagonist ICI82780 (females), an aromatase inhibitor or androgen antagonist flutamide (males) during the early postnatal window or during puberty and the same dependent measures will be assessed. Finally, to evaluate how organizational effects of steroids are manifested, the number of dopamine neurons, density of innervation, dopamine content and electrically-stimulated dopamine release in nucleus accumbens and caudate nucleus will be determined following the same treatments. These studies should provide insight into potential biologic mechanisms that influence gender differences in diseases related to dopamine neuronal function in humans including Parkinson's disease and psychostimulant addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENDER, SEX STEROIDS AND DRY EYE SYNDROMES Principal Investigator & Institution: Sullivan, David A.; Schepens Eye Research Institute Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 30-SEP-1985; Project End 30-NOV-2001 Summary: The preocular tear film plays a critical role in maintaining ocular surface integrity, protecting against microbial challenge and preserving visual acuity. Tear film dysfunction, in turn, may severely impact the eye and lead to desiccation of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and pronounced visual impairment and blindness. Countless people suffer from tear film disorders, which are termed dry eye syndromes and are classified into 2 major types: aqueous-deficient and evaporative. Aqueous- deficient dry eye is due to decreased tear secretion from the lacrimal gland. An example is Sjogren s syndrome, a common autoimmune disease that afflicts primarily women and destroys the lacrimal gland. Evaporative dry eye is typically caused by meibomian gland dysfunction and may be a major cause of dry eye during menopause and aging. The long range objectives of this grant application are to test our hypotheses that: (1) androgens are extremely important in the physiological regulation of the lacrimal and meibomian glands, as well as the production of the tear film; and (2) gender, sex steroid hormones, and in particular androgen deficiency, are critical etiologic factors in the pathogenesis of both aqueous-deficient and evaporative dry eye syndromes. Experimental procedures involve mouse and rabbit models, differential display techniques, RT-PCR, cloning, Northern and Southern blots, in situ hybridization, cell cultures, immunoassays, HPLC/mass spectrometry, enzyme assays, histology, image analysis, hormone reconstitution experiments, as well as clinical studies with humans. Our specific aims are to: (1) define the mechanism(s) underlying the androgen-induced suppression of lacrimal gland inflammation in mouse models of Sjogren s syndrome; (2) identify the genes and proteins involved in the androgen control of the rabbit meibomian gland; (3) determine whether androgens regulate the lacrimal and meibomian glands of humans; (4) examine whether a correlation exists between total androgen deficiency and dry eye syndromes in women with Sjogren s syndrome; and (5) evaluate whether the human lacrimal and meibomian glands contain the enzymatic machinery necessary for the local synthesis and action of sex steroids. Results from the studies should significantly advance our understanding of the processes by which gender and sex steroids influence the anterior segment of the eye. In addition, findings may have health relatedness for the eye, because they: (1) explore the regulation of the tear film; and (2) may lead to the development of specific therapies for the clinical treatment of dry eye syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENDER-SPECIFIC NEUROANATOMY
ONTOGENIC
COCAINE
EFFECTS:
Principal Investigator & Institution: Dow-Edwards, Diana L. Professor; Physiology and Pharmacology; Suny Downstate Medical Center 450 Clarkson Ave New York, NY 11203 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JAN-2007 Summary: Previous work has demonstrated that a brief period of cocaine exposure produces long-term functional alterations in components of the mesolimbic and nigrostriatal dopamine systems which depend on the gender of the rat. In males, postnatal day (PnD) 11-20 cocaine causes a dampening of the responsivity of the mesolimbic system primarily due to a disruption in D1-mediated cellular events. In females, the mesolimbic system appears to function normally but the nigrostriatal system does not. Gonadal hormones appear to be most significant in females since recent studies show that gonadectomy does not interact with cocaine in males while ovariectomy before cocaine administration dampens cocaine's effects in females. Aim 1 of this proposal will determine the role of ovarian hormones in producing cocaine's effects. First, the critical hormone will be identified in females and then the long term neurochemical, molecular and behavioral effects of PnD 11-20 cocaine administration in ovariectomized females will be established. Since 2DG studies show that adult males postnatally exposed to cocaine exhibit relative independence of functional components of the dopaminergic circuits, Aim 2 will examine the coupling of metabolism and behavior following amphetamine sensitization in PnD 11-20 cocaine-exposed males and females. Aim 3 will expand the scope of this work by drawing on findings from clinical studies of cocaine exposed children. Cocaine will be administered both pre and postnatally and brain metabolism and behavior will be assessed in offspring focusing on anxiety, arousal, and cognition, all previously demonstrated to be affected by either pre and/or postnatal cocaine in our lab. Together these studies will examine the neuroanatomic basis for developmental cocaine's effects on function in males and females and determine the roles of gonadal steroids in producing these effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICALLY ENGINEERED VIRUSES FOR BRAIN TUMOR THERAPY Principal Investigator & Institution: Martuza, Robert L. Chief of Neurosurgery; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 31-MAR-2003 Summary: We have proposed the development of genetically engineered viral vectors that can selectively and efficiently infect and kill brain tumor cells in situ without harming surrounding brain cells and without causing systemic disease and have focused on conditionally-replicating mutants of herpes simplex virus-1 (HSV-1) which we have genetically engineered to be attenuated for neurovirulence. We developed the vector, G207, a multimutated HSV-1 that conditionally replicates in glioblastoma, malignant meningioma, and other tumors but is non-neuropathogenic in HSV-sensitive mice and subhuman primates. Safety and efficacy studies have been done to allow G207 to be considered for human trial. We have also demonstrated that G207 can induce a specific cell-mediate immune response to tumor cell surface antigens and that this can be boosted with the introduction of cytokines such as IL-12 into a defective vector grown with G207 as a helper virus. We now plan studies to optimize this treatment. We will study factors with possible adverse effects on the clinical use of HSV for brain tumor therapy such as the effects of co- treatment with steroids and the consequences of
Studies 47
prior exposure to HSV on the efficacy of HSV-tumor therapy. Tumor models in mice will be used to test. The effects of exposure to steroids or of prior exposure and seropositivity to HSV. In order to improve the specificity of targeted tumor cell destruction, we also construct and test transcriptionally targeted HSV vectors for selective destruction of cells expressing nestin or midkine. In order to improve the treatment of cells at a distance from virus inoculation, we will also explore the use of HSV vectors expressing cytokines, immune co-stimulatory molecules such as B7-1 and/or a suicide gene, or a combination of these in order to modulate the host immune system to optimize brain tumor therapy with HSV. Through our first grant, we have developed the first HSV vector that can be safely used for brain tumor therapy. Through these studies we expect to create the next generation of HSV vector with improved efficacy and selectivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOMIC & NONGENOMIC EFFECTS OF STEROIDS ON SALT INTAKE Principal Investigator & Institution: Sakai, Randall R. Associate Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, OH 45221 Timing: Fiscal Year 2001; Project Start 01-JUL-1995; Project End 31-MAR-2005 Summary: (applicant's abstract): The expression of sodium appetite in the rat is controlled by a multitude of hormonal mechanisms evoked when the animal is sodium depleted. Research has shown that it is not the sodium deficiency itself but rather the synergistic action of angiotensin and aldosterone, hormones that are released in response to the sodium depletion, which 1) generate the appetite for salt, and 2) have long-term effects that enhance subsequent salt intake. The proposed experiments examine the genomic and non-genomic effects of steroids on sodium intake and are based upon a foundation of past research examining the neurohormonal basis of sodium intake in the rat. This research proposal attempts to extend the current understanding of how and where these hormones act in the brain to elicit their specific behavioral effects by using A) site specific directed stimulation of brain parenchyma by steroids to: 1) identify those brain areas sensitive to adrenal steroids in eliciting sodium intake, and 2) to examine the mechanism by which the steroids act, i.e., either by classical genomic actions on the neurons that require hours of activation prior to eliciting a behavioral response or by acting at putative membrane receptors such that changes in behavior occur within minutes after steroid application; and B) by using current cell and molecular biological techniques in an in viva preparation to examine the effects of selective interference of endogenous steroid and peptide receptor production in brain. In addition to increasing our understanding of a classic instance of self-regulatory behavior, this research has health relevance. These results may provide rational therapies for patients in whom sodium intake complicates the management of hypertension and renal disease. With a better understanding of how endocrine mechanisms operate in eliciting sodium intake, chemical therapies that interfere with the actions of the/hormones can be directed at different levels of its production or mechanisms of action to reduce the craving for sodium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLOMERULAR PERMASELECTIVITY IN STEROID RESISTANT NEPHROTIC SYNDROME Principal Investigator & Institution: Myers, Bryan D.; Stanford University Stanford, CA 94305
48 Steroids
Timing: Fiscal Year 2001 Summary: Focal segmental glomerular sclerosis (FSGS) is an often progressive form of nephrotic syndrome responsible for 10-15% of end-stage renal disease in children. Patients with FSGS are often resistant to oral steroid therapy, necessitating the use of very aggressive alternative treatments (high-dose intravenous steroids, cyclophosphamide, plasmapheresis). Some patients will respond with remission only after months of this intensified therapy. It would be of great value to be able to predict the severity of disease early in its course, to avoid subjecting patients with less malignant disease to overly aggressive therapy, while starting such therapy promptly in patients likely to have the most resistant disease. Our study is designed to examine the glomerular hemodynamics, macromolecular permeability and quantitative pathology (stereology) of pediatric patients with steroid-resistant nephrotic syndrome or biopsyproven FSGS, in order to distinguish at disease onset those patients who will require aggressive therapy from those in whom a more extended course of routine oral steroids may eventually lead to persistent remission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSE MEATBOLISM IN THE HUMAN OVARY Principal Investigator & Institution: Charron, Maureen J. Professor of Biochemistry; Biochemistry; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2003; Project Start 20-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): GLUT4 is the main insulin responsive glucose transporter in adipose and muscle which plays an important role in regulating glucose metabolism. While not sensitive to regulation by sex steroids, GLUT4 is commonly decreased in insulin resistant states. GLUTx1, also known as GLUT8, is a recently discovered glucose transporter that appears to be sex steroid regulated. It is expressed in human ovary and inhibited by sex steroids in human testis. These results suggest a sex steroid regulation of GLUT8 expression and a possible involvement of GLUT8 in the provision of glucose required for metabolic processes and DNA synthesis in germ cells. Glucose transport activity, could be an important determinant of metabolic as well as reproductive function in women. Alterations in peripheral as well as ovarian glucose transporters could be directly related to insulin resistance and perhaps to reproductive dysfunction. The relative expression of peripheral and ovarian GLUT4 and GLUT8 in women with Polycystic Ovarian Syndrome (PCOS) and normally cycling women has only partially been characterized. Alterations of GLUT8 and GLUT4 could provide insight into the pathophysiology of PCOS. To clarify the role of glucose transporters (e.g. GLUT8 and GLUT4) in normal and PCOS ovaries, the following Specific Aims are proposed. Aim 1 will examine the regulation of glucose transport and GLUT8 and GLUT4 expression/localization in a steroid-producing cell line to test the hypothesis that GLUT8, and not GLUT4, is sex steroid regulated within the ovary. Novel human ovarian theca-like and granulosa-like cell lines (HOTT and HGL-5 cells, respectively) will be used. Additionally, the ability of rosaglitazone (insulin sensitizer) to improve glucose uptake and transporter expression/localization in these cells will be assessed. Aim 2 will determine the expression and cellular localization of glucose transporters in normal human ovary. Aim 3, concurrent with Aim 2, will test the hypothesis that the ovarian expression of GLUT8 and GLUT4 is decreased in women with PCOS relative to normally cycling age- and BMI-matched controls. Aims 2 and 3 will be carried out by a prospective, case-control study of women with PCOS undergoing ovarian drilling/wedge resection for fertility and a group of normally cycling women undergoing elective tubal sterilization. Immunohistochemistry, immunoblots and RT-
Studies 49
PCR/real time PCR will be used to determine the expression and cellular localization of GLUT8 and GLUT4 in different tissues. The proposed studies are expected to provide mechanistic insight into the regulation of glucose transport within the ovary in women, an area that has been essentially unexplored. These observations are hoped to have relevance for understanding of basic reproductive physiology and the mechanism of reproductive dysfunction in PCOS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GNRH GONADOTROPIN TRANSCRIPTION AND STEROID FEEDBACK Principal Investigator & Institution: Shupnik, Margaret A.; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2003; Project Start 23-APR-2003; Project End 31-MAR-2008 Summary: GnRH pulses and sex steroids act on the pituitary to regulate the synthesis and secretion of LH and FSH. In the past funding period, we cloned the rat alphasubunit promoter, identified GnRH-responsive DNA elements and transcription factors for rat LHbeta and alpha-subunit promoters, and characterized intracellular signaling pathways mediating GnRH responses. The LHbeta promoter requires pulsatile GnRH stimulation in vivo, and has two cooperating complex DNA elements, a distal element with overlapping Sp1 and CArG box sites, and a proximal element with two bipartite sites for SF-1 and Egr-1. Both elements bind Sp1 family zinc finger proteins that could differentially affect transcription. Relative roles of these transcription factors in GnRH stimulation will be assessed by DNA-protein binding, chromatin immunoprecipitation (CHIP) and real-time RT-PCR, and transfection ot deletion/mutation luciferase constructs in LbetaT2 ceils. Preliminary data show that steroids both enhance (17betaestradiol (E) or pM dihydrotestosterone, DHT) and suppress (nM DHT) the GnRH transcriptional response, without steroid receptor binding to DNA. Coactivator/integrator proteins SNURF and CBP will be tested in cotransfection and protein-protein binding studies for modulation of the GnRH response. Parallel biochemical and functional strategies will be used to investigate both stimulatory and suppressive effects of steroids in normal gonadotropes and LbetaT2 cells. These include tests of altered promoter occupancy by Sp1/Egr- 1 family members in ChIP assays, rescue of suppression by overexpression of transcription factors, and alteration of gene expression by focused microarray analysis and real-time RT-PCR. Promoter regions and transcription factors mediating steroid responses will be defined. Nuclear receptor requirements will be tested with steroid antagonists, and the Tfm androgen receptor mutant mouse. Non-genomic steroid effects on intracellular signaling pathways will be measured in the absence or presence of GnRH. These studies will further our understanding of GnRH regulation of the gonadotropins, and steroid modulation of this response. This research has important implications for understanding fertility disorders such as PCOS, in which elevated circulating androgens are accompanied by altered GnRH and LH secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GROWTH FACTORS IN FOLLICULAR DEVELOPMENT Principal Investigator & Institution: Roy, Shyamal K. Professor; Obstetrics and Gynecology; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2001; Project Start 01-JUL-1992; Project End 31-MAY-2003
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Summary: (adapted from the applicants abstract) The use of isolated intact follicles in long term culture provides an alternative to culture of isolated cellular components of follicles. This method allows for the study of proliferating cells in their more natural follicular environment. These follicles synthesize cAMP and steroids, proliferate and respond to gonadotropins as well as express gonadotropin receptors and unique proteins. In addition, this model shows that the mitogenic action of FSH is mediated via the action of epidermal growth factor (EGF). The research plan during the past 4 years and in the proposed future grant focuses on preantral follicles about which little is known in comparison to antral follicles. The investigator has established that hamster follicular cells express EGF, transforming growth factors beta (TGF-beta1 and -beta2), EGF and TGF-beta receptors. The goal of the present proposal is to define the role(s) of hormones and growth factors in modulating the expression of EGF and TGF-beta receptors, and the functional implications of growth factor receptor expression during follicular development as a mechanism regulating folliculogenesis. The working hypothesis is that one of the mechanisms of growth factor regulated follicular development involves a negative interaction of EGF-R and TbetaR, the expressions of which act as a pivotal determinant to direct follicular cells either to proliferation or to functional differentiation (e.g., onset of androgen and estrogen synthesis)--two most fundamental requirements for follicular development. Growth factor receptor expressions in follicular cells, in turn, is critically regulated by gonadotropins, ovarian steroids and growth factors themselves. The hypothesis will be tested on preantral and antral follicles exposed to endogenous hormones in cyclic hamsters, on preantral follicles deprived of hormonal support in long term hypophysectomized (HX) hamsters, and on preantral follicles from cyclic and HX hamsters cultured in vitro in the presence of gonadotropins, ovarian steroids, EGF and TGF-beta using: (1) immunohistochemical and biochemical analyses of follicular cell proliferation, and growth factor receptor expression, (2) analysis of follicular steroidogenesis, and (3) quantitative RT-PCR analyses of TGF-beta receptor gene transcripts. The information will shed light on the mechanisms involved in hormonal control of folliculogenesis via intraovarian growth factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GUIDELINES FOR STEROIDS IN CHILDREN WITH LUPUS Principal Investigator & Institution: Brunner, Hermine I. Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2003; Project Start 08-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): BACKGROUND: This is a pilot study to evaluate the use of steroids and other medications in children diagnosed with SLE (cSLE). After having revolutionized the prognosis of lupus in the 1950s, steroids remain the mainstay of therapy of cSLE. Recent studies suggest that, despite their proven benefits, steroids contribute to the development of permanent disease damage in both adult and pediatric SLE patients. 10-year patient survival is only at 85%. Preliminary data support that there is a considerable degree of practice variation among pediatric rheumatologists treating cSLE and that these differences in treatment approach may have an impact on patient outcomes. There are no published guidelines of how to best treat cSLE, especially how to use steroids for its the treatment and when to introduce other steroid-sparing medications. GOALS: 1) To document treatment patterns of pediatric rheumatologists for patients with cSLE in order a) To identify key factor that prompt physicians to choose a certain steroid dose and document the factors that make physicians change a given dose of steroids; b) To identify the key variables that prompt physicians to
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introduce of immunosuppressive therapies for patients diagnosed with cSLE. 2) To measure quality of life and specific outcomes (damage, costs) associated with the treatment of children and adolescents diagnosed with cSLE. STUDY DESIGN: A cohort of consecutively sampled patients treated for cSLE (n=70) at 4 pediatric US and Canadian Rheumatology Centers (Chicago, Cincinnati, Minneapolis, Toronto) will be assessed in at least tri-monthly intervals over an 18-month period regarding their disease course (disease activity, number of flares, infection and hospitalization), treatments, and outcomes (damage, quality of life). Key determinants that prompt the physicians to use certain therapies will be recorded. Relevant retrospective patient information will be obtained by chart review. Patient quality of life and treatment costs will be measured. Correlation, regression, multivariable modeling including repeated measure analysis will be used to analyze the relationship of cSLE therapies to outcomes (damage, quality of life, costs) and to key determinants of treatment decisions in cSLE. SIGNIFICANCE: The proposed pilot study will provide information regarding physician treatment patterns, cost of cSLE and patient quality of life. Data will be collected to support that there are important differences in the approach to cSLE therapy that have a significant impact on patient outcomes. Results of the study will be used to generate hypotheses towards improved treatment approaches for cSLE. The proposed study constitutes a first step towards the development of evidence-based guidelines. Information on HRQL and costs of patients diagnosed with cSLE is required for future cost-effectiveness analyses of treatments for cSLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL CONTROL OF FEMALE REPRODUCTIVE TRACT Principal Investigator & Institution: Brenner, Robert M. Senior Scientist; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001 Summary: This research aims to increase our understanding of the stromal-epithelial interactions that mediate the action of steroids in the reproductive tract. Our studies focus on the regulation and effects of specific growth factors, and on specific enzymes called matrix metalloproteinases (MMPs). Our studies have progressed in three main areas. First, we have characterized two novel forms of hepatocyte growth factor (HGF) expressed in the macaque endometrium. These two truncated transcripts of HGF are similar to two variants (HGF/NK1 and HGF/NK2 ) that are reported for the human genome. Northern blot of total RNA from microdissected, estradiol-treated endometrium showed that HGF/SF mRNA was expressed at 10 fold higher levels in the functionalis than in the basalis zone. In situ hybridization confirmed this expression gradient and showed that specific signal was confined to the subepithelial and perivascular stromal cells. Second, we immunocytochemically localized expr ession of two forms of vascular endothelial growth factor (VEGF) receptor, Type I (FLT1) and Type II (flk1/KDR) in the macaque endometrium. FLT1 staining was detected on the endothelial surface of small vessels and muscles of larger spiral arteries. Arterial staining was strongest in monkeys treated with estradiol plus progesterone (E2 + P), suggesting that VEGF may play a role during luteal phase artery growth. KDR staining was also evident in vascular endothelial cells. However, when P was withdrawn at the end of the cycle, a wave of strong KDR staining was observed in the stromal cells of the upper functionalis zone. KDR in stromal cells may play a functional role in remodeling the endometrium at the end of the menstrual cycle. Third, a critical period of P withdrawal is required to induce menstruation. We have evaluated expression of various matrix metalloproteinases (MMPs) during and after the critical period. When P
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is replaced during the critical period, expression of M MP-1, MMP-2, MMP-3, and TIMP 1 are blocked. However, when P is replaced after the critical period, some but not all MMPs are blocked. This indicates that MMPs vary both in their sensitivity to P suppression and their importance in menstruation. FUNDING NIH HD19182 PUBLICATIONS Lindsey JS, Brenner RM. Rhesus macaque endometrium expresses two novel transcripts of hepatocyte growth factor/scatter factor. Biol Reprod (Suppl 1) 58:173 (abstract 324). Lindsey JS, Slayden OD, Brenner RM. A zonal gradient of hepatocyte growth factor/scatter factor expression in rhesus macaque endometrium. Mol Biol Cell 9:477a,1998 (abstract). Rudolph-Owen LA, Slayden OD, Matrisian LM, Brenner RM. Matrix metalloproteinase expression in Macaca mulatta endometrium Evidence for zone-specific regulatory tissue gradients. Biol Reprod 59:1349-1359, 1998. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL CONTROL OF PROLIFERATION Principal Investigator & Institution: Thompson, E A. Professor of Human Biological Chemistry; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001; Project Start 01-AUG-1987; Project End 30-JUN-2005 Summary: Glucocorticoids kill both normal and malignant lymphoid cells. Consequently, steroids of this class remain a principle tool in chemotherapy of both malignant and non-malignant lymphoproliferative diseases. Glucocorticoids also mediate normal immune development and differentiation, and are very important pharmacological and physiological modulators of the immune response. Virtually all individuals in the United States will use glucocorticoids for some purpose during their life. Nevertheless, we do not understand the mechanisms whereby such steroids affect proliferation and death of either normal or transformed lymphoid cells. This proposal presents a cogent hypothesis to explain how glucocorticoids kill malignant T lymphoid cells, and is a continuation of more than 20 years of work in this area. We have determined that glucocorticoids inhibit the expression of cyclin D3. This is a posttranscriptional process in which the degradation of cyclin D3 mRNA increases rapidly upon addition of dexamethasone. Destabilization involves at least two proteins that bind to a defined response element within the 3' untranslated region of cyclin D3 mRNA. Approximately half of the project (Specific Aim 1) deals with isolation and characterization of these two proteins, analysis of their mechanism of action, and identification of other proteins that may participate in glucocorticoid-mediated destabilization of cyclin D3 mRNA. We have determined that inhibition of cyclin D3 expression causes a redistribution of the cyclin-dependent kinase inhibitor, p27Kip1, which dissociates from Cdk4-containing complexes as the abundance of cyclin D3 falls and binds to and inhibits cyclin E/Cdk2 complexes. We have recently discovered that the antiapoptotic protein Bc12 is a substrate for Cdk2. Inhibition of Cdk2 by glucocorticoids and other agents causes net dephosphorylation of Bcl2. We propose that dephosphorylation of Bc12 leads to cell death, perhaps by decreasing the affinity of Bc12 for Bax, favoring the formation of Bax homodimers and cell death. The remaining half of this proposal (Specific Aim 2) deals with testing this hypothesis. We will analyze the phenotype of cells that express dominant negative Cdks and p27, with particular attention to Bc12 phosphorylation and cell death. We will also analyze the phenotype of cells that express Bc12 mutants that cannot be phosphorylated as well as mutants that mimic constitutive phosphorylation. Upon completion of these specific aims. we hope to have, for the first time, a mechanism that accounts for the relationship between glucocorticoid inhibition of Cdk2 activity, cell proliferation, and cell death.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL REGULATION OF BRAIN MATURATION Principal Investigator & Institution: Stonestreet, Barbara S. Professor; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, RI 02905 Timing: Fiscal Year 2000; Project Start 01-JUL-1997; Project End 31-DEC-2003 Summary: The importance of the hypothalamic-pituitary-adrenocortical axis in the transition to extrauterine life is well-known. This axis potentially also exerts regulatory influences upon the developing brain. Recent evidence suggests that antenatal corticosteroid (steroid) therapy for fetal maturation reduces the incidence of intraventricular hemorrhage. Thus, this axis is most likely important in brain maturation. Nevertheless, the effects antenatal steroids on the developing brain have not been well documented. This proposal examines the hypotheses that antenatal steroids matue physiologic and improve pathophysiologic brain development. Physiologic, histlolgic, biochemical and molecular methods are combined in the following Specific Aims: Aim 1 examines the effect of antenatal steroids on blood-brain barrier (BBB) function in fetal and newborn lambs. BBB permeability is quantified by the integral technique to 14 C-alpha-aminooisobutyric acid. The hypothesis to be tested is that antenatal steroids accelerate maturation of the blood- brain barrier. Aim 2 examines the effect of steroid pretreatment on brain volume regulation in fetal, newborn and adult sheep. Brain volume, water and electrolytes, are measured by standard methods and graded osmotic stress achieved with mannitol. The hypothesis to be tested is that steroid preteatment improves brain volume regulation in fetuses and newborns. Aim 3 examines the effect of steroid pretreatment on Na+, K+-ATPase activity and specific isoform gene expression in brain and choroid plexus. We will also examine whether these increases correlate directly with maturational effects of steroids on brain volume regulation. Aim 4a examines the potential neuroprotective effects of antenatal steroids on brain ischemia in the fetus. After antenatal steroids or placebo, brain ischemia is induced by bilateral carotid artery occlusion after ligation of the vertebro-occipital anastomoses. Fetal cerebral perfusion and metabolism are measured before, after 40 minutes of ischemia, and sequentially during 48 hrs of reperfusion. Cerebrospinal fluid injury markers, brain lipid peroxidation products, histology and immunohistochemistry will define brain injury, and brain water and electolytes tissue edema. The hypothesis to be tested is that antenatal steroids attenuate brain injury in the fetus. Aim 4b examines the effect of antenatal steroids on Na+,K+-ATPase activity and gene expression in ischemic and normal brain, as in Aim 3. The hypothesis to be tested is that antenatal steroids attenuate ischemia-related decreases in Na+,K+-ATPase activity and gene expression. The proposed studies will provide important information on the effects of antenatal steroids on physiologic and pathophysiologic cerebrovascular and brain maturation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONE REGULATION OF PAIN PERCEPTION Principal Investigator & Institution: Quinones, Vanya; Hunter College 695 Park Ave New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: Gender differences have been observed in pain and opioid sensitivity. In general, females have lower nociceptive thresholds and achieve less analgesia from morphine-like (mu) opioids. During different reproductive stages female rats experience
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different pain thresholds, suggesting that the hormonal environment may modulate their nociceptive responses. The proposed studies will examine pain and opioid sensitivity in ovariectomized (OVX) rats with and without steroid replacement Behavior and gene expression will be concurrently examined. We will measure not only the response to an acute thermal stimulus (tail flick) but also models of subacute (formalin and intrathecal, IT NMDA) and chronic (nerve constriction) nociception and a test for mechanical sensitivity. Because the glutamatergic receptor system is an important modulator of pain sensitivity in animals and humans and in the development of morphine tolerance, we will examine this system together with the opioid system. Steroids can have powerful effects on gene expression and therefore we will measure their effects on glutamate and opioid receptors and neuropeptide mRNA and protein levels. The project will be conducted as an integrated mentoring and collaborative relationship between investigators at Hunter College of the City University of New York and Weill Medical College of Cornell University of New York and Weill Medical College of Cornell University. The Quinones' group will focus on understanding the role of steroids in the modulation of pain (nociception-tail flick and formalin tests) and opioid (mu and kappa) sensitivity (acute, development of tolerance and efficacy of NMDA receptor antagonists). The Inturrisi group will train Quinones' group in, not only the techniques necessary to produce the pain and opioid tolerance models, but also in the design and analysis (e.g., dose-response) of the proposed studies. The mentoring experience will extend to Hunter College students, who will have the opportunity to obtain further training in this area of neuroscience resulting in the expansion of neuroscience research at Hunter. The research expertise acquired through the mentoring-collaborative interactions will ensure that Dr. Quinones is more competitive in obtaining future independent funding. Research into the mechanisms underlying gender differences in pain and opioid sensitivity is of considerable interest since it can reveal systems, e.g., hormonal which modulate pain and opioid responsiveness, and therefore can provide a new understanding of how females cope with the aversive stimuli that may accompany copulation, parturition, and nursing. The proposed studies may also provide new insights into pain management approaches for females including those utilizing estrogen or progesterone based contraceptives or estrogen replacement treatment after menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN ENDOMETRIAL NITRIC OXIDE: REGULATION AND FUNCTION Principal Investigator & Institution: Khorram, Omid A. Associate Visiting Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (Provided by Applicant): Nitric oxide (NO) is a free radical with diverse physiological functions one of which is its smooth muscle relaxant effects. By virtue of this effect NO plays a key role in regulating vascular tone and therefore 1: flow to many organs including the reproductive tract. Recent identification of predominantly endothelial nitric oxide synthese (eNOS) in the human uterus with primary localization to the endometrial glands has raised the possibility that this molecule may have functions other than regulation of blood flow, such as control of endometrial glandular secretion. Additionally, the marked increase in the endometrial expression of eNOS mRNA and protein around the expected time of implantation with a decline just prior menstruation suggests that endometrial eNOS is regulated by sex steroids, and plays a role in implantation process. In this proposal we will test the hypothesis that sex
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hormones regulate endometrial eNOS, and NO in turn functions as a mediator of estrogenic influence on cellular proliferation, progesterone's effect in induction of endometrial decidualization. To test our hypothesis we will use in vitro approach using primary human derived endometrial cells to test the direct effects of estrogen progesterone and their combination on eNOS expression and NO secretion (Specific Aim 1) Using pharmacological tools to block the synthesis of endometrial NO, and transfection studies to upregulate eNOS gene expression we will determine if NO mediates E and P actions in the endometrium or independent of sex steroids influence cellular proliferation and endometrial secretion of decidual products (Specific Aims 2 and 3). To complement these studies we will use an ex vivo approach to determine if patients with implantation failures may have endometrial eNOS defects Specific Aim 4). This pilot study should shed light on regulation and function of human endometrial NO pathway, an uninvestigated area of research with profound clinical significance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERPOLARIZED ASTHMATICS
HELIUM-3
MRI
OF
THE
LUNG
IN
Principal Investigator & Institution: De Lange, Eduard E. Professor of Radiology; Radiology; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2004 Summary: (Verbatim from the Applicant's Abstract): Asthma is an important public health concern affecting more than l4 million people in the United States including over 4.8 million children. Epidemiological studies show a trend toward increasing prevalence and morbidity, but the reasons for these increases remain unclear. Asthma is a chronic disease defined by reversible obstruction of the small airways, inflammation, and increased airway responsiveness to a variety of stimuli: a process that disrupts adequate ventilation of the alveoli causing dyspnea and hypoxia. Existing methods of small airways disease are either indirect or imprecise. Hyperpolarized helium-3 (H3He) gas MR lung imaging is a new technology which allows direct visualization of the lung airspaces, the ventilation and small airway disease, enabling assessment of disease activity at a level that was previously impossible to evaluate. Thus, H3He MR imaging has the potential to provide insight into the pathophysiology of asthma and to contribute to improved clinical management. Preliminary studies with H3He MR have demonstrated ventilation defects in asthmatics, even when they were asymptomatic and had normal lung function tests, and the findings suggest that this new technology is capable of detecting subclinical disease. The goal of the proposed research is to gain a better insight into the H3He MR imaging characteristics in asthmatics (Specific Aim # 1) and to determine how these findings correlate with disease activity and severity (Specific Aim #2). In order to obtain information on the imaging characteristics, we will evaluate the H3He MR imaging findings in populations of symptomatic and asymptomatic asthmatics, using healthy, non-asthmatics as controls. In addition, we will determine in small subgroups of patients how these findings compare to those obtained with two existing lung imaging modalities, nuclear medicine ventilation scanning and computed tomography (CT). To determine the ability of H3He lung MR in assessing disease activity, we will evaluate the imaging changes that occur during tests that provoke (worsen) and treat (improve) asthma. Provocation tests include inhalation of methacholine, exercise, administration of endobronchial allergen and viral inoculation, and treatments include inhaled of p2agonist (albuterol) and steroids (asthmacort). The results of the studies proposed in this research will serve as a foundation for developing future clinical and basic research applications.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF GONADAL STEROID UPON SEROTONERGIC FUNCTION Principal Investigator & Institution: Berga, Sarah L. Professor and Chair; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: Objective: Gonadal steroids are important modulators of neuronal function and associated behavioral states. Sex steroid excursions have been implicated in premenstrual dysphoric disorder, postpartum depression, perimenopausal and menopausal mood changes, Alzheimer's Disease (AD), and overall cognitive function. A critical neuronal system mediating mood and cognition is serotonin. Methods to directly assess the effects of sex steroids upon central serotonergic function in humans are expanding with the development of specific serotonin radioligands. Through PET imaging with the 5-HT 2a radioligand [18F]altanserin, we aim to demonstrate that estrogen will upregulate central serotonin function, while progesterone will further modify the effects of estrogen. We also aim to explore the relationships between central 5-HT 2a receptor density, platelet 5-HT 2a and 5-Ht 2a density, and tests of neuropsychological function to determine the sample size needed for future studies to test hypotheses about the interrelationship of these variables. Design: Seven physically and mentally healthy menopausal women will receive 10 weeks of estrogen followed by 2 weeks of combined estrogen progestersone replacement. At three time intervals (baseline, following 10 weeks of unopposed estrogen treatment, and following 2 weeks of combined hormone treatment), subjects will undergo studies of neuropsychological functioning, blood sampling for platelet, serotonin activity, and PET studies with the 5HT 2a ligand[18F]altanserin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INHALED STEROID ADHERENCE IN MODERATE & SEVERE ASTHMA Principal Investigator & Institution: Apter, Andrea J. Associate Professor of Medicine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 10-SEP-2000; Project End 31-AUG-2005 Summary: Candidate's Plans/Training: I, Andrea J. Apter, MD, MSc, plan a change in career emphasis from clinician-educator to an independent investigator in asthma clinical research. I want to use my extensive clinical experience and recent prior training in clinical epidemiology to better understand how social setting with its barriers to treatment influences disease. The training is designed to fill my knowledge gaps and will be interdisciplinary. it will include advanced formal course work in epidemiology, biostatistics, behavioral science, and health services research along with structured mentoring as I conduct the proposed research project. Environment: The University of Pennsylvania is an environment uniquely suited for this training award. its Center for Clinical Epidemiology and Biostatistics will provide structured mentoring and formal coursework. The Leonard Davis institute is a renowned center for health services research and the Annenberg School is a center for behavioral science research. The Pulmonary, Allergy, Critical Care Division serves a large, diverse patient population and has a record of outstanding clinical research. Research: Given the substantial morbidity and mortality associated with asthma and the proven efficacy of inhaled steroids in reducing this morbidity and mortality, identifying solutions for the problem
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of poor adherence to inhaled steroid regimens takes on great urgency. Recent research indicates low socioeconomic status and inadequacy of physician-patient communication are predictors of poor adherence. The low-income inner city asthma population is at high risk for poor clinical outcome. This project identifies potentially modifiable sociobehavioral factors that impede adherence to inhaled steroid regimens with a focus on the inner city poor population. The central hypothesis is that mutable social and behavioral factors influence adherence and that adherence can be improved by modifying these factors. This project has two phases, an observational cohort study and a randomized intervention. Phase I has 2 aims. We will identify potentially modifiable sociobehavioral barriers associated with poor adherence using electronic monitoring and controlling for disease activity and socioeconomic status (Aim 1). A behavioral model of adherence will be employed to formulate and test hypotheses. Aim 2 will examine how fluctuations in adherence influence asthma severity measured by electronic monitoring of nighttime use of a short-acting beta-agonist. In Phase II we will implement a randomized controlled pilot trial to improve adherence (Aim 3). Possible interventions that will be studied include the effect of enhanced patient-physician communication using electronic monitoring data and/or an educational program on improving adherence. This intervention will be designed taking into account the results of the cohort study performed in Phase I of this training program. Upon the foundation of my prior clinical experience and education, this training program is designed to equip me with the additional skills and research experience necessary to become a fully independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LABELING THE NEUROACTIVE STEROID SITE OF GABBA RECEPTORS Principal Investigator & Institution: Sawyer, Gregory W. Molecular & Med Pharmacology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 24-JAN-2001 Summary: The primary objective of the research proposed in this fellowship application is to further the understanding of neuroactive steroid and anesthetic action at the GABA/A receptor by photoincorporating novel radiolabeled neuroactive steroid and anesthetic ligands into purified recombinant GABA/A receptor of known subunit composition. The data collected during this investigation will provide valuable information for understanding the molecular targets of general anesthetics and for modeling the allosteric effects of both neuroactive steroids and general anesthetics at the GABA/A receptor. Specifically, a novel neuroactive steroid anesthetic photolabel (HBPP) will be used to label amino acids within or near the binding site for neuroactive steroids on recombinant alpha1beta2gamma2 GABA/A receptor purified from Sf9 cells. Following photoincorporation, the subunits of the receptor are separated using SDSPAGE and the labeled subunit(s) is fragmented using V8 protease. The fragments generated from protease digestion are identified using photoaffinity labels and antibodies that bind to known domains of GABA/A receptor subunits and are then sequenced. Following the identification of the amino acid residue(s) bound by HBPP, chimeras and site-directed mutants at or near the area bound by HBPP will be generated to verify the contribution of the labeled amino acid to the binding and/or action of neuroactive steroids. This mutational analysis has the potential to identify amino acids not labeled by HBPP that contribute to neuroactive steroid binding and/or action. The general anesthetics promegestone, azi- octanol, and etomidate will also be used as
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photolables to label amino acid residues within or near the anesthetic binding site at recombinant alpha1beta2gamma2 GABA/A receptor. The identification of amino acid residues bound by these anesthetics will proceed as described above. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LENS MEMBRANE STEROID BINDING PROTEIN (MSRP) Principal Investigator & Institution: Cenedella, Richard J. Biochemistry; Kirksville College of Osteopathic Med 800 W Jefferson St Kirksville, MO 63501 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-MAY-2003 Summary: Chronic therapeutic use of steroid hormones to treat a variety of inflammatory conditions carries a high risk of cataracts, even in children. There is no consensus on the mechanism of steroid induced cataracts and disagreement on whether the lens contains classic steroid receptors. The purpose of this project is to exploit a serendipitous observation to provide a fresh approach to exploring the basis of steroid induced cataracts. We discovered a 28 kDa membrane protein present in the epithelium of lenses from several species, including humans, that binds steroids with high affinity. This protein, originally discovered in liver microsomal membrane, is purported to be a new type of steroid receptor and is termed the membrane steroid binding protein (MSBP). We hypothesize that this protein mediates nongenomic actions of steroids on the eye, actions which can contribute to lens opacification. Our broad goals are to clone the genes for this protein (which may be prenylated), described the protein's steroid hormone binding characteristics and the types of steroid actions the protein may mediate. Based upon partial sequence information, primers were used to amplify, clone and sequence a 290 bp segment of the MSBP which was subsequently digoxigenin labeled. This probe will be used to screen cDNA libraries from bovine, rat and human lens for the genes of MSBP. The structure of the coded protein(s) will be deduced, including identification of prenylation sites. The lens epithelial cell membrane fraction responsible for binding steroids will be identified by enzyme analysis and Percoll gradient distribution. Is it plasma or microsomal membrane? Binding studies using radiolabeled steroids will be conducted to establish the binding hierarchy of steroid hormones, principally glucocorticoids, relative to the standard, 3H-progesterone. The capacity of steroids to induce "rapid"-nongenomic effects on lens cells will be evaluated by measuring the capacity of steroids to affect epithelial cell free calcium levels (using Fura-2 fluorescence spectroscopy), Na+/K+- ATPase (using ouabain inhibitable 86Rb uptake), apoptosis measured by the TUNEL assay and in vivo rates of lens epithelial cell migration and differentiation following pulse labeling with 3H-thymidine. Preliminary findings and published data support the possibility that steroids can rapidly elevate intracellular calcium and inhibit Na+/K+-ATPase activity in lens epithelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LOCATING GENERAL ANESTHETIC SITES IN ACETYCHOLINE RECEPTORS Principal Investigator & Institution: Cohen, Jonathan B.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001 Summary: Locating General Anesthetic Sites in Acetylcholine Receptors We wish to identify the sites of binding of representative general anesthetics when they are acting as inhibitors of nicotinic acetylcholine receptors (AcChoRs). The anesthetics to be studied include steroids, which are likely to act at the protein-lipid interface, alcohols and
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barbiturates, that may act within the ion channel domain, and halothane, a volatile anesthetic that may interact with novel regions of the AcChoR that are important for the gating of the ion channel by agonists. Mapping studies will be carried out with AcChoRs in nicotinic postsynaptic membranes isolated from Torpedo electric organ. Radio-labeled, photo- activatable anesthetics will be covalently incorporated into AcChoRs and labeled AcChor subunits will be isolated and degraded so that the sites of labeling can be determined by N-terminal protein sequence analysis of the labeled peptides. These structural studies provide a definition of the amino acids and regions of the AcChor that tare in contact with the anesthetics. but they do not assess the functional importance of these sites of contact. To address this for steroid antagonists, we will characterize interactions of progesterone and progesterone analogs with wild type and mutant AcChoRs expressed in Xenopus oocytes to identify structural determinants important for drug potency and to determine how mutations within different AcChoR functional domains alter drug potency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LOW RENIN HYPERTENSION Principal Investigator & Institution: New, Maria I.; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001 Summary: Adrenal steroid secretion and metabolism are being studied to define the role of adrenal steroids in various hypertensive disorders of childhood. Under-standing the pathophysiology of childhood hypertension will permit specific modes of therapy to be devised and may prevent irreversible hypertension. Adrenal steroid secretion and metabolism are being studied to define the role of adrenal steroids in various hypertensive disorders of childhood. Under-standing the pathophysiology of childhood hypertension will permit specific modes of therapy to be devised and may prevent irreversible hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MALE REPRODUCTIVE PHYSIOLOGY IN THE HUMAN Principal Investigator & Institution: Crowley, William F. Professor; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2002; Project Start 01-JUL-1981; Project End 30-JUN-2007 Summary: (provided by applicant): Using the human disease model of men with idiopathic hypogonadotropic hypogonadism (IHH), it is possible to: a) control the timing and pace of their testicular maturation via administration of either exogenous gonadotropins or pulsatile GnRH; b) manipulate their gonadal sex steroid hormonal milieu by administration of steroid hormone inhibitors; and c) vary the dose and frequency of their hypothalamic input of GnRH. This ability to clamp the hypothalamic input to their pituitary via GnRH and contrast the responses of IHH men with those of normal and castrate men (whose hypothalamic-pituitary-axis is unconstrained) allows us to dissect the hypothalamic from pituitary sites of action and address several physiologic issues that are not otherwise approachable in the human. Thus, In Specific Aim #1, we will thus explore the relative roles of gonadal sex steroids and Inhibin B (IB) in restraining FSH secretion across the full spectrum of gonadal development were serum IB levels vary from prepubertal levels to those of normal adult men. Our preliminary results suggest that their relative roles appear to change during gonadal maturation. It also permits us to understand the role of the frequency of GnRH in FSH
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feedback and thus place it in context with both sex steroids and lB. In Specific Aims # 2 & 3, this model allows us to test the ability of FSH to increase Sertoli and germ cell number, testicular size, and sperm counts when administered to IHH men with immature gonads and compare these results with those obtained when FSH stimulation is accompanied by that of LH via pulsatile GnRH therapy. During such studies we will also have access to testicular tissue in these men and thus can validate both MIS and IB as markers of Sertoli cell numbers, proliferation, and maturation in a quantitative and statistically valid fashion that has not been previously possible. In collaboration with Dr. Martin Dym, we will perform quantitative histomorphometry on these maturing gonads via serial testicular biopsies prior to and following 4 months of therapy and correlate these histological findings with serial measurements of IB and MIS as well as other clinical and biochemical aspects of gonadal maturation. Finally, in Specific Aim #4, the availability of serial testicular tissue in these men during Sertoli and early germ cell development will allow us to gain insight into the specific genes activated in the human during early testicular development. Thus, these studies offer a unique approach to gain new insights into the physiology and developmental biopsy of the male reproductive axis. They also lay the groundwork that provides a context for the exploration of new tools to gain further insights into the complexities of reproductive dysfunction in the male. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISTIC STUDIES OF PRO-APOPTOTIC BENZODIAZEPINES Principal Investigator & Institution: Glick, Gary D. Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2004 Summary: (Principal Investigator's Abstract) Systemic lupus erythematosus (SLE) is a multisystemic autoimmunune disorder of unknown etiology. Many patients afflicted with SLE develop a severe nephritis mediated by the localization of immune complexes within glomeruli. Current treatments of this nephritis and other symptoms of the disease center on the use of steroids or cytotoxic immunosuppressive agents. While effective in some patients, these agents are non-specific and can cause serious side effects that often force discontinuation of treatment. We have identified a benzodiazepine (1) that does not bind to the central benzodiazepine receptor, which shows significant efficacy in treating the glomerulonephritis and other symptoms of disease in both (NZB x NZW)F1 and MRL/MpJ-lpr/lpr mice, the two most clinically relevant animal modes of human SLE. Both in vitro and in vivo experiments demonstrate that this benzodiazepine selectively induces apoptosis in lymphocytes directly responsible for autoimmune (B and T cell) mediated inflammation. At therapeutic doses, treatment suppresses the autoimmune response without altering normal immune function or evidence of side effects. Further development of 1 into a clinically useful agent requires a better understanding of both how this molecule induces cell death, and by what means apoptosis of lymphocytes results in disease improvement. To address this need, we propose to characterize the effects 1 has on cellular immune function by determining the phenotype of lymphoid cells killed by 1 in vivo and in vitro. Phenotypic analysis will be based on plasma membrane determinants and cytokine expression. Next, to uncover the mechanism by which 1 functions, we will identify the sub-cellular systems (e.g. caspases, mitochondria and other components of death response) triggered to execute 1-mediated cell death. Lastly, we will isolate the receptor of 1 based on yeast three-hybrid screening. If 1 is lethal to yeast, we will pursue an alternative strategy of mutagenesis followed by classical yeast genetics and
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functional cloning to generate resistant strains and identify molecules necessary for 1induced death. The resistant strains developed will then serve as host strains for the three-hybrid system. These experiments will complement on-going efforts to identify the receptors(s) for 1 using more traditional affinity chromatography methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLEC RECOGNITION IN INTESTINAL LIPID BINDING PROTEINS Principal Investigator & Institution: Cistola, David P. Assistant Professor; Biochem & Molecular Biophysics; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 30-NOV-2002 Summary: This project involves the study of several intracellular lipid-binding proteins from the small intestine. These proteins have distinct specificities, stoichiometries and affinities for fatty acids, steroids, retinoids and eicosanoids, but the basis for these differences is unclear. The long-term goal of this research is to define the rules that govern molecular recognition in this protein family. The specific aims are (1) to characterize a panel of mutants designed to perturb the dynamic portal of rat and human intestinal fatty acid-binding protein (I-FABP); (2) to engineer variants of rat and human I-FABP with increased affinity for fatty acids, and to develop prototype highaffinity ligands for wild-type I-FABP; (3) to engineer a second- generation helix-less variant of I-FABP and use it as a model system for investigating the determinants of lipid-binding specificity; (4) to characterize the interactions between a physiologically relevant bile salts and ileal lipid-binding protein (I-LBP); and (5) to determine the 3D structures and backbone mobilities of human I-LBP with and without bound bile salts. The experimental approach employs triple-resonance NMR, fluorescence spectroscopy and isothermal calorimetry to characterize these proteins and their complexes with lipids. Definition of the roles for lipid-protein recognition may lead to the design of specific high affinity inhibitors with therapeutic potential in type II diabetes and hypercholesterolemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISM Principal Investigator & Institution: Crews, Fulton T. Director, Bowles Center for Alcohol Stu; Center for Alcohol Studies; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-1997; Project End 30-NOV-2002 Summary: This Alcohol Research Center Grant (ARC) is focused on the unifying hypothesis that common cellular and molecular events caused by ethanol lead to alterations in cellular signaling that trigger tissue specific pathologies. Interdisciplinary research themes include studies on cellular signaling, calcium levels, steroids, gene regulation, transcription factor activation, oxidative stress behavioral responses to ethanol and the use of gene delivery to investigate and/or modify the effects of ethanol. The ability to study single cell types in vitro complements and strengthens studies of molecular signaling events in specific brain regions. The pathologies associated with alcoholism represent a central theme that is divided into two foci, tissue pathology and the pathological processes that regulate alcohol seeking behaviors. This ARC connects 15 funded research projects focused on molecular and cellular processes that underlie the pathogenesis of alcoholism and alcohol toxicity. Oxidative tissue damage is a focus
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of several components and cores that link eight currently funded research projects together within this Center to test the hypothesis that oxidative stress is a major mechanism of ethanol toxicity. Components within the ARC will study free radical production, cytosolic calcium signaling, mitochondrial calcium and membrane potential, activation of transcription factors NFkappaB and APl, cytokine formation and the activation of kinase signaling cascades. The interaction of CYP2EI, reperfusionoxygen tension and other determinants of oxidative stress will be related to apoptosis and cell death. Factors that determine gene expression and transcription factor activation will connect liver, brain, fetus and pancreas. Three components of this ARC will focus on brain and bridge together seven active research projects studying the cellular and molecular mechanisms that promote addictive behavior. The molecular mechanisms that control brain reward systems and ethanol withdrawal sensitization will be studied to elucidate the pathogenesis of alcohol addiction in brain. The signaling pathways involved in these processes will be determined by following transcription factor formation, induction of immediate early genes, regulation of ethanol sensitive receptor genes and the ability of steroids and delivered genes to modulate ethanol self administration, preference and dependence. Gene delivery will be used to modify transcription factor activation and GABAa receptor sensitivity as well as to deliver antioxidants and enzymes that enhance neurotransmitter synthesis. Models of chronic ethanol administration, eg. Tsukamoto-French, repeated ethanol withdrawal, chronic self administration, will be shared among components providing greater insight into the aspects of ethanol consumption that contribute to toxicity. Studies of both males and females are included in several components to better understand the role of gender and steroid hormones m ethanol pathology, particularly since steroids appear to modulate ethanol dependence and the free radical capacity of cells. These studies build on existing knowledge in different tissues and cellular systems that allow molecular and cellular hypothesis on ethanol toxicity to be specifically tested. Studies in multiple cellular and tissue systems strengthen the ability of investigators to explore new avenues to uncover the molecular mechanisms of alcohol pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS FOR GENDER SELECTIVE EFFECTS OF ETHANOL Principal Investigator & Institution: Devaud, Leslie L. Associate Pharmaceutical Science; Idaho State University Pocatello, ID 83201
Professor;
Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 30-JUN-2004 Summary: The goal of this proposal is to characterize the molecular basis for gender differences underlying ethanol dependence. The objective is to test the hypothesis that gender influences neuroadaptations of GABA and glutamatergic systems elicited by chronic ethanol exposure. GABAA and NMDA receptors are key sites in the brain mediating the effects of ethanol. Ethanol dependence results in subunit selective alterations in gene expression and function for both GABAA and NMDA receptors. We have recently found profound gender differences in the effects of chronic ethanol consumption on GABAA receptor alpha and NMDA NR1 subunit expression. This shows that gender impacts the effects of ethanol dependence on gene expression for these two key neurotransmitter systems. This suggests that neuroadaptations associated with ethanol dependence and withdrawal may be dependent on the hormonal context of the ethanol exposure. However, there is little evidence showing a direct association between ethanol dependence and withdrawal behaviors and the molecular changes observed for GABAA and NMDA receptors. The proposed studies will investigate the
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molecular basis for gender differences in the effects of ethanol dependence and withdrawal by correlating the development of and recovery from ethanol dependence with changes in gene expression and receptor regulation. This proposal will test the hypothesis that ethanol dependence induces gender-selective alterations in 1) GABAA receptor regulation, function and gene expression, 2) NMDA receptor regulation, function and gene expression, and 3) levels of several key neuroactive steroids. We will determine whether these alterations show a temporal correlation with behavioral manifestations of ethanol dependence and withdrawal. These studies are particularly important as the expression of neuroadaptations to chronic ethanol consumption varies according to gender, even though both genders display similar behavioral signs of dependence and withdrawal. It is critical to ascertain whether the timing of functional or molecular changes in GABAA or NMDA receptors are associated with physiological manifestations of dependence and withdrawal, including the influence of differing endogenous regulation. These investigations are important for understanding the neurobiological basis of ethanol dependence and withdrawal in both males and females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MODELING OF HUMAN P450C17 & P450C21: ADRENARCHE, ANDROGEN Principal Investigator & Institution: Auchus, Richard J.; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001 Summary: Cytochrome P450c17 (17-hydroxylase, 17,20-lyase) catalyzes both the 17hydroxylation and oxidative cleavage of C21 steroids in both human adrenal glands and gonads. These two activities, however are independently regulated in vitro and in human physiology by such factors as phosphorylation and the allosteric effect of cytochrome b5. P450c21 is a related steroidogenic enzyme that catalyzes the 21hydroxylase reaction. P450c17 and P450c21 have high sequence similarity and identical gene structures, and both utilize the same substrates (pregnenolone, progesterone, and their 17-hydroxy derivatives). The subtle differences in their substrate selectivities and catalytic specificities lead to the production of different steroid hormones with vastly different biological activities. We believe that structure-function comparisons of the two enzymes will yield important insight to the actions of steroidogenic enzymes and approaches to their selective inhibition. We have completed a computer-graphic model of human P450c17 based on the X-ray structure of the bacterial P450BM-P using the resources at the UCSF Computer Graphics Laboratory. Based on our analysis of the P450c17 model using the CGL resources, we have designed chimeric proteins in an attempt to confer 21-hydroxylase activity to P450c17 and 17-hydroxylase activity to P450c21. We have also analyzed several structures of cytochrome b5 and apocytochrome b5 in the CGL. Based on this analysis, plus our biochemical studies, we are engineering mutant forms of b5 which we will use to probe the interaction of P450c17 with b5. We will use these data to refine the model and to dock protein surfaces together, with the goal of describing the structure of the entire catalytic complex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR STRUCTURE OF STEROIDS Principal Investigator & Institution: Duax, William L. H.A. Hauptman Distinguished Scientist; Hauptman-Woodward Medical Research Inst 73 High St Buffalo, NY 14203 Timing: Fiscal Year 2001; Project Start 01-DEC-1979; Project End 30-NOV-2002
64 Steroids
Summary: The goals of this project are to achieve a molecular level understanding of the biological and physiological events surrounding steroid synthesis, function and metabolism and to use this knowledge to facilitate the development of safe, effective drugs for use as steroid agonists and antagonists in controlling fertility, cancer chemotherapy, and the treatment of hypertension, atherosclerosis and other steroid hormone related disorders. X-Ray crystal structure determinations of hormonal steroids and the proteins with which they interact are being undertaken, and correlations between molecular conformation and biological activity are being elucidated. The Molecular Structure of Steroids Project has generated hundreds of steroid crystal structures in collaboration with biochemists, pharmacologists, and endocrinologists, provided answers to specific questions about steroid synthesis and activity, produced an empirical model for steroid hormone receptor binding and activity, revealed unanticipated conformations of the most potent progestins, estrogens and corticoids, and produced 164 manuscripts, 34 chapters and two volumes of the Atlas of Steroid Structures in which the structural determinations were reported and their significance discussed. The immediate goals of the project are the determination of the threedimension structures, the mechanisms of action and inhibition and the basis for hypertension, and neoplasia (bacterial 3alpha, 20beta- hydroxysteroid dehydrogenase, 3alpha,20beta-HSD; porcine 20beta- hydroxysteroid dehydrogenase, 20beta-HSD; human 17beta-hydroxysteroid dehydrogenase, 17beta-HSD; porcine 20beta-11betahydroxysteroid dehydrogenase, 11beta-HSD) a microbial cholesterol esterase (Cc ChE) of relevance to atherosclerosis, and a mammalian prostatic binding protein (PBP) implicated in prostate cancer therapy. The complex of 3alpha,20beta-HSD and a licorice analogue will be used to model inhibition of mammalian 11beta-HSD and 15-hydroxy prostaglandin dehydrogenase (15-HPD). Inhibition of the former induces hypertension and of the latter combats peptic ulcers. The structure of 20beta-HSD will allow us to improve our models for the NADP-dependent 11beta-HSD and 15-HPD. The comparison of the active sites of 3alpha,20beta-HSD and 20beta-HSD should explain why 20beta-HSD does not accept corticosteroids with oxygen substituents at C(11) as substrates. The architecture of the active site revealed by X-ray analysis of 17beta-HSD will be compared with that in the observed structures of 3alpha,20beta-HSD and 20betaHSD and the modeled structure of 11beta-HSD in order to identify features that determine 17beta specificity and might be exploited in designing active site directed inhibitors of potential use in breast cancer therapy. A comparison of the structure of Cc ChE with those of other esterases should reveal the basis for cholesterol specificity and permit design of specific inhibitors of ChE that would block hydrolysis of cholesterol esters thereby controlling cellular uptake. The structure of PBP will reveal the molecular architecture of the heterodimer and the nature of binding of estramustine and foster the design of drug-steroid conjugates that might be selectively delivered to the prostate for cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MONOAMINE AND RELATED REGULATORY SYSTEMS IN TOURETTE'S Principal Investigator & Institution: Ciliax, Brian J. Neurology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (Verbatim from the Applicant's Abstract) A prominent theory of the pathophysiology of Tourette Syndrome (TS) is based on abnormal function of monoaminergic (e.g. dopaminergic, serotonergic, and noradrenergic) pathways in basal
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ganglia. The abnormality may lie within the neurochemistry of the "primary" monoaminergic systems themselves or that of "secondary" systems (e.g.) gonadal steroid receptors or oxytoxin and vasopressin pathways that project to basal ganglia), which regulate the basal ganglia or their monoamine afferents. Monoamines have been implicated in TS by metabolic abnormalities, increased dopamine transporter binding, and effective treatment with dopamine receptor blockers. However, gonadal steroids and their peptidergic effector systems also may be involved, since male to female ratios are disproportionate, changes in steroid hormone levels alter tic severity, and androgen antagonist were efficacious in preliminary trials. Moreover, steroid hormones and oxytocin and vasopressin pathways have distinct sex differences, have distinct ontogenic events that could account for the chldhood onet of TS, and regulate monoaminergic circuits and related locomotor and limbic behaviors. The goal of this research proposal is to determine if there are neurochemical alterations in either of these primary and secondary circuits that could cause the pathophysiology of TS. The specific neurochemicals to be studied will be the plasma membrane transporters for dopamine (DAT), sertonin (SERT), and norepinephrine (NET), and the vesicular monoamine transporter (VMAT2), gonadal steroid receptors (androgen (AR) and estrogen (ER)), and receptors for oxytocin (OT-R), and vasopressin (V1a). The specific techniques to be used include immunocytoghemistry quantitative immunoautoradiography, quantitative immunoautoradiography, quantitative counting methods, and quantitative radioligand binding autoradiography in postmortem TS brain tissue. Our transporter analysis will focus on the respective monoaminergic neurons in brainstem and their terminal fields in basal ganaglia, whereas the steroid receptor and neuropeptide receptor analyses will focus on parvocellular oxytocin and vasopressin neurons in paraventricular nucleus of hypothalamus and bed nucleus of stria terminalis/medial amygdala complex, and their terminal fields in brainstem monoamine cell groups and basal ganglia. The findings of this study will help elucidate the neurochemical changes that occur in TS and might suggest novel therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DERIVATICES
MULTICOMPONENT
COUPLING--STEROIDS
/ETOPOSIDE
Principal Investigator & Institution: Herndon, James W. Associate Professor; New Mexico State University Las Cruces Las Cruces, NM 880038001 Timing: Fiscal Year 2001 Summary: The major objective of this proposal is to explore a series of novel synthetic reactions which culminate in new synthetic routes to pharmaceutically-important aromatic and heteroaromatic compounds, including synthetic steroids, etoposide anticancer drugs, and 2-arylfuran natural products. The reaction under investigation involves the coupling of highly conjugated acetylene derivatives with Fischer carbene complexes, and is divided into two sections: coupling of carbene complexes with enzyme-carbonyl compounds, and coupling complexes with conjugated enediynes. The major focus involves exploration of the coupling of Fischer carbene complexes with enyne-carbonyl compounds, which provides the biologically-important furan ring system in a single step. Extension of the reaction to aromatic systems will lead to the unstable isobenzofuran ring system, which can undergo high-yielding a predictable reactions with electron-deficient alkenes. Exploitation of this reaction for the single step synthesis of the steroid ring system provides a remarkable versatile method to prepare a diverse array of steroid derivatives for biological testing. A similar reaction process can provide rapid synthetic routs to the structural analogs of the anti-cancer drug etoposide.
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The other area to be investigated is the coupling of conjugated enediynes with Fischer carbene complexes. This reaction process affords aromatic diradical intermediates, and a major effort will be made to understand and control the reaction pathways of the free radical intermediates. A major feature of these reaction processes is the selective introduction of functional groups into unfunctionalized alkyl chains. Use of this reaction for the synthesis of 2-arylfuran natural products will also be investigated. The field of synthetic organic chemistry has had a profound impact on human health. Investigation of the synthesis of pharmaceutically- important molecules can provide analogs, which are useful for maximizing the desired pharmacological effects and for a better understanding of the mode of action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NASAL STEROIDS & CHRONIC FATIGUE SYNDROME INDUCED SLEEP DISTURBANCE Principal Investigator & Institution: Craig, Timothy J. Associate Professor; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, PA 17033 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL AND BEHAVIORAL ACTIONS OF ANABOLIC STEROIDS Principal Investigator & Institution: Clark, Ann S. Psychological & Brain Scis; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 10-DEC-1993; Project End 30-JUN-2004 Summary: (Adapted From The Applicant's Abstract): The long-term objective of this project is to elucidate the neural and behavioral actions of anabolic-androgenic steroid(s) (AAS). Although the majority of published research focuses on males, it has been shown that women and adolescent girls take AAS to improve athletic performance and to achieve a muscular physique. We have demonstrated that individual AAS have discrete and quantifiable effects on the estrous cycle and sexual receptivity in adult rats. The goal of the present proposal is to extend our analysis of AAS effects to include motivation for sexual behavior and to delineate the physiological mechanisms by which AAS affect the nervous system in female rats. First, we will broaden our analysis of AAS effects on female sexual behavior and physiology and address the following questions: (a) does prepubertal AAS administration alter the onset of puberty and produce short- or longterm changes in estrous cyclicity or fertility, (b) do AAS given in combination act synergistically or antagonistically to alter the estrous cycle or sexual behavior, and (c) do AAS alter sexual behaviors that underlie motivation that may be comparable to libido in humans? Second, we will test the role of three brain areas (ventromedial hypothalamus, preoptic area, and lateral septum) rich in androgen and estrogen receptors, in the inhibition of sexual behavior by AAS. Specifically, (a) does direct application of AAS to these brain regions produce effects on behavior that mimic systemic administration, and (b) does the ability of AAS to modulate sexual behaviors at these central sites depend on signaling through steroid (androgen or estrogen) receptors? Third, we will test the possibility that AAS may alter sexual behaviors by acting at gamma-aminobutyric acid type A (GABAa) receptors, because transmission mediated by the GABAergic system is known to modulate sexual behavior. Expressly, does the central administration of AAS modulate sexual behaviors via effects on neuroendocrine processes underlying the AAS modulation of female sexual behavior. Characterizing AAS effects on the central
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nervous and endocrine systems in laboratory animals will provide valuable scientific evidence that will improve our understanding not only of the physiological and behavioral responses to high dose AAS abuse in women, but also to other naturally occurring disorders that are accompanied by androgen excess, such as polycystic ovarian syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL STEROIDOGENIC ENZYMES AND BRAIN FUNCTION Principal Investigator & Institution: Schlinger, Barnett A. Assistant Professor; Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (applicant's abstract): Steroids have profound effects on the development and function of the brain. Traditionally, the brain is viewed as a target for action of sex steroids synthesized in the gonads, or to a lesser degree the adrenals, since each of these organs express all the enzymes that catalyze the conversion of cholesterol into the active sex steroids. In the last two decades, evidence has emerged indicating that some steroidogenic enzymes could be found in the central nervous system, suggesting that the brain itself could synthesize the active steroidal signaling molecules. Nevertheless, despite their identification in brain tissue, there is little evidence confirming a functional role for these enzymes in brain. We believe that steroids synthesized in brain may contribute to the organization and activation of specific behaviors in songbirds. Behavioral and neuroanatomical studies show that some steroid-dependent functions occur in songbirds in the absence of detectable steroid signaling from the periphery. These functions may be activated by a local, non-systemic steroidal signal. We have obtained support for this hypothesis in that we have found neural expression and/or activity of all 4 steroidogenic enzymes (CYP11A1, 3B-HSD, CYP17, and CYP19) required for the conversion of cholesterol to progestins, androgens, and estrogens in adult zebra finches, including expression of all enzymes in cerebellar Purkinje cells. The goal of these studies is to explore this hypothesis more fully by determining 1) if mRNA for each steroidogenic enzyme in brain is translated into functional protein, especially in Purkinje cells of adult zebra finches; 2) if neural expression of steroidogenic enzymes is associated with the organization of the neural song control circuit and with song learning in developing zebra finches and song sparrows, and 3) if neural expression of steroidogenic enzymes is associated with the activation of sex steroid-dependent behavioral functions when circulating steroids are basal in adult song sparrows. We believe these studies will contribute significantly to our understanding of the steroidogenic capability of the brain, and expand concepts of steroids as neural signaling molecules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROENDOCRINE CONTROLS OF SALT APPETITE Principal Investigator & Institution: Fluharty, Steven J. Professor of Pharmacology; Animal Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 15-FEB-1997; Project End 31-DEC-2006 Summary: (provided by applicant): Body fluid and cardiovascular homeostasis depend on the coordinated regulation of complementary physiological and behavioral mechanisms. The principle behaviors that ensure stability of the volume and composition of the fluid matrix are thirst and salt appetite. Accumulating evidence
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strongly supports a major role of the renin-angiotensin-system (RAS) in control of both of these motivated behaviors. Moreover, steroid hormones regulate the brain's responsivity to angiotensin II (AngII) and thus the arousal of water and salt intake. In the present application we investigate the cellular and molecular mechanisms underlying two well established examples of these hormonal interactions: 1) estrogen regulation of AngII-induced thirst; and 2) corticosteroid potentiation of salt appetite. In each of these examples we focus on the signaling properties of AngII receptors in a major receptor zone, the subfornical organ (SFO), gene expression within neuronal projections from the SFO to the paraventricular nucleus (PVN) and dorsal perifornical lateral hypothalamus (dpLHA), and activation of these effector pathways that subserve behavioral and complementary neurohypophysial function. Collectively, these studies will provide a more complete understanding of the neuroendocrinology of body fluid homeostasis, as well as elucidate fundamental principles of steroid/neuropeptide interactions governing behavior. More specifically, we will test these hypotheses: (i) Adrenal and ovarian steroids regulate thirst and salt appetite by modulating AngIIreceptor mediated signal transduction in discrete brain regions; (ii) Adrenal and ovarian steroids regulate thirst and salt appetite by modulating gene expression within separate populations of AngII-responsive SFO neurons that project to hypothalamic nuclei; (iii) Changes in endogenous levels of adrenal and ovarian steroids, as occur during hypovolemia and the estrus cycle, regulate gene expression in the same SFO projections to hypothalamic nuclei; and, (iv) The genes regulated by ovarian steroids are important for neurotransmission in the SFO axonal projections to hypothalamic regions that control water and salt consumption as well as neurohypophysial secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURONAL DYSFUNCTION IN PREMENSTRUAL DYSPHORIC DISORDER Principal Investigator & Institution: Epperson, Cynthia N. Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 05-DEC-1999; Project End 30-NOV-2004 Summary: After a year and a half on the faculty in the Departments of Psychiatry and Obstetrics and Gynecology, I find myself at a crossroads in my career development. I have been involved primarily in clinical postpartum mood disorders and obsessive compulsive disorders research. However, my clinical and scientific interests have shifted. During my tenure as the Director of the Yale Behavioral Gynecology Program, I have developed an appreciation for the complex interplay between neuroactive steroids and the neurochemistry involved in regulation of mood and cognition. In addition, I have developed basic skills in proton-magnetic resonance spectroscopy (1H-MRS), a novel, non-invasive method to quantify in vivo amino acid neurotransmitters. I have designed the K23 award to enable me to pursue a five-year comprehensive researchtraining plan. This plan will provide me with the skills necessary to become an independent investigator who can apply MRS techniques to determine the impact of neurosteroids on GABA and glutamate neurotransmission as they reltate to the pathophysiology and treatment of premenstrual dysphoric disorder (PMDD). Without support from a K23 award, I would be required to continue my significant administrative and clinical duties as the director of a busy clinical program and would not be afforded the opportunity to make this shift in my scientific career. We have obtained exciting pilot data using 1H-MRS demonstrating fluctuations in cortical GABA levels across the menstrual cycle of women with PMDD and health menstruating controls with between group differences in the fluctuation pattern. I propose to continue
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these investigations with three goals. 1) To conduct the first longitudinal (across the menstrual cycle) characterization of both frontal and occipital cortex GABAergic and glutamatergic systems in healthy menstruating women and those with PMDD. 2) To determine the relationship between neuroactive steroids and amino acid neurotransmitter levels across the menstrual cycle. Amd 3) To determine whether the selective serotonin reuptake inhibitor fluoxetine exert its therapeutic effect in the treatment of PMDD via modulation of neuroactive steroids and/or GABAergic and/or glutamateric function. I have identified several key areas where I will require additional training in order to advance the use of 1H-MRS techniques to the study of PMDD. These areas include; 1) nuclear magnetic resonance application of reproductive endocrinology to PMDD research, 3) neurochemistry and kinetic modeling, and 4) neuropharmacology and clinical trials methodologies. Under the mentorship of my Yale mentors Drs. Krystal, Rothman, and Naftolin and my extra-mural mentors Drs. Rubinow and Schmidt, the career development program outlined in this program is certain to prepare me for a career as an neuroendocrinologist who can utilize MRS technology to study the impact of neuroactive steroids on brain neurochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROREHABILITATION PREGNENOLONE
WITH
PROGESTERONE
&
Principal Investigator & Institution: Wright, David W. Emergency Medicine; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): There are about 5.3 million people in this country living with a range of disabilities caused by traumatic brain injury, and about 25-30% of those people are unable to return to work one year later. At present, there are no effective clinical treatments currently available to the victims of traumatic brain injuries that can repair the primary and secondary damage caused by the cascade of cytotoxic damage unleashed by the initial insult. Obviously, a safe, low cost and effective treatment for such a significant health problem is worth addressing. Numerous reports have documented the role of neurosteroids in immediate post-injury neuroprotection. However, few studies have examined the effect of these steroids as a treatment after the acute phase. We are particularly interested in the effect of progesterone long-term because it is currently being tested in a human clinical trial as an acute phase neuroprotectant. Extensive preclinical trials have shown that progesterone is neuroprotective when administered shortly after injury. However, at least two of the potential mechanisms (inhibition of NMDA transmission and stimulation of GABAA receptors), by which progesterone exhibits neuroprotection, could potentially worsen subacute rehabilitation and subsequent long-term recovery. Conversely, pregnenolone, the precursor of progesterone, exhibits opposite effects with respect to NMDA and GABAA modulation and could enhance neurorehahilitation. We propose to determine the effects of progesterone and pregnenolone when treatment is delayed after injury in animals. The data gathered would provide information regarding the potential utility of these neurosteroids in subacute or long-term treatment conditions. In addition, should progesterone prove to be an effective neuroprotectant in the human clinical trial, it will be necessary to know how long treatment should be maintained and whether long-term treatment enhances or deters post-injury rehabilitation. There is a growing body of evidence that both progesterone and pregnenolone can also stimulate remyelination of damaged nerve cells and that they also have the potential to stimulate neuronal repair after the initial injury cascade has long subsided. This means that these steroids, both of
70 Steroids
which are synthesized in the brain, may be beneficial as adjunct therapies for long-term rehabilitation. We propose to investigate the role of the neurosteroids progesterone (PROG) and pregnenolone-sulfate (PREGS) as putative treatment for traumatic brain injury during the rehabilitation phase of recovery in both male and female subjects. Therefore, we will examine two delayed treatment paradigms (7 days & 28 days post injury) on the recovery process at the behavioral and morphological levels of analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROSTEROIDS: BIOSYNTHESIS AND REGULATION Principal Investigator & Institution: Soma, Kiran K. Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-APR-2001 Summary: Steroids, such as testosterone and estradiol, have dramatic effects on the brain. Research has traditionally focused on sex steroids produced by the gonads and adrenals. However, recent data indicate that the brain and spinal cord can also produce steroids ("neurosteroids"). Data are accumulating on the locations of steroidogenic enzymes in the brain and on neurosteroid levels in the brain. However, the regulation and functions of neurosteroids remain unclear. The regulation of steroidogenic enzymes in the brain may be critical for their function, as in the gonads and adrenals. This proposal addresses the regulation of neural steroidogenic enzymes in the avian brain. The first study will assess the effects of gonadectomy on the expression of genes for steroidogenic enzymes in brain, using in situ hybridization, Northern blots, and RTPCR/Southern blots. The second study will investigate the regulation of neural steroidogenic enzymes in vitro. In primary cell cultures, regional differences in enzyme activities will be measured in both sexes. The effects of cAMP and sex steroids on enzyme activities will also be tested. These data will fill critical gaps in the new field of neurosteroids and be relevant for understanding the regulation of neurosteroids in the other vertebrates, including humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC OXIDE EFFECTS ON BRONCHOPULMONARY DYSPLASIA Principal Investigator & Institution: Bland, Richard D. Professor of Pediatrics; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract) Bronchopulmonary dysplasia (BPD) often complicates prolonged mechanical ventilation after premature birth. Defining the mechanisms that cause BPD and developing a safe, effective treatment strategy are the ultimate objectives of this project. To study the pathogenesis of BPD and to test various therapeutic interventions, we developed a preterm lamb model that mimics the clinical and pathological findings of this disease. The underlying hypothesis is that early postnatal inflammation of the immature lung exposed to prolonged, repetitive stretch with 02enriched gas leads to oxidant and protease induced lung injury that can be inhibited or prevented by early and continuous postnatal delivery of inhaled nitric oxide (iNO), the response to which may be enhanced by antenatal steroid treatment. The proposal has 3 specific aims: (i) to compare immediate vs delayed (7d) postnatal delivery of continuous, low-dose iNO (and the relevant control, no iNO) in chronically ventilated preterm lambs; (ii) to determine if antenatal steroid treatment will modify the response to immediate or delayed iNO; and (iii) to determine if iNO will inhibit lung inflammation and thereby facilitate postnatal adaptation of the pulmonary circulation
Studies 71
and respiratory tract, leading to improved respiratory gas exchange. This project complements the clinical trial of iNO in preterm infants with respiratory failure. Serial specimens of bronchial secretions, lung lavage fluid and lung lymph will allow assessment of inflammation in evolving BPD. The research plan includes physiological, biochemical, histological and molecular techniques to define mechanisms underlying abnormalities in the lung circulation (persistent elevation of vascular resistance, edema from increased vascular filtration pressure, loss of the pulmonary vasodilator response to iNO, increased arterial smooth muscle, reduced numbers of microvessels and less capillary surface density, decreased expression of endothelial nitric oxide synthase and soluble guanylate cyclase); respiratory tract (increased expiratory resistance, proliferation of bronchiolar smooth muscle, reduced numbers of alveoli); and lung interstitium (increased lung tropoelastin expression and disordered elastin accumulation) that characterize the lamb model of BPD. Collaborative studies with other SCOR projects that focus on surfactant proteins and function (I), vascular endothelial growth factor and its receptors (II), inflammatory mediators (III), and mitogens that influence smooth muscle proliferation and connective tissue elements (IV) will provide new insight on mechanisms of lung dysfunction and dysplasia in BPD and the impact of iNO and antenatal steroids on these abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NONGENOMIC SIGNALING BY STEROIDS AT THE CELL MEMBRANE Principal Investigator & Institution: Hammes, Stephen R. Assistant Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): A longstanding question in steroid physiology is how steroids mediate nongenomic, or transcription-independent, effects. Examples of rapid, steroid-triggered nongenomic signaling are myriad, including estrogen-mediated up-regulation of nitric oxide synthase (NOS) in endothelial cells, vitamin D-induced calcium mobilization in osteosarcoma cells, and progesterone-induced maturation of frog and fish oocytes. These signaling events may mediate important biological functions such as blood vessel relaxation, bone metabolism, and fertilization. Unfortunately, most of these processes are part of complex biological systems that are difficult to manipulate in vitro, which presents a serious problem when trying to understand the biology behind them. This proposal uses the phenomenon of steroidinduced maturation of frog oocytes as an experimental model for studying nongenomic steroid signaling. The maturation of an oocyte refers to the meiotic stage at which an oocyte rests. "Immature" oocytes are arrested in prophase of meiosis I, while "mature" oocytes rest in metaphase II. Steroids induce this re-entry into the cell cycle via a transcription-independent process that appears to involve membrane bound classical steroid receptors and possibly signaling via G proteins. Although controversial, the primary physiological mediator of oocyte maturation in Xenopus appears to be the androgen, testosterone. This system offers many advantages in studying nongenomic signaling by steroids. Steroid-induced oocyte maturation is reproducible, easy to detect, and biologically relevant. Furthermore, oocytes are easily manipulated in vitro for protein expression and signaling studies. The aims of this proposal are: 1) to improve our knowledge of the early signaling pathways induced by steroids in oocytes, including the role of G proteins, in the maturation process; and 2) to elucidate the role of the classical androgen receptor in the maturation process. Understanding nongenomic steroid-induced signaling in oocytes should prove helpful in elucidating the
72 Steroids
mechanisms involved in other nongenomic signaling pathways and may lead to new insights toward controlling their associated biological processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL NEURON STEROIDAL INTERACT MODEL IN SEIZURE INDUCT IMPLICAT FOR EPILEPSY Principal Investigator & Institution: Grove, Kevin L.; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001 Summary: Changes in ovarian steroids alter brain functions, such as mood, anxiety, cognition and neural degeneration. However, the mechanisms by which these steroids alter neuronal function only now are being understood. The focus of our study is to determine the mechanisms by which progesterone and suckling stimuli interact in the lactating rat to provide neuroprotection against seizure induction and neuronal damage in the hippocampus (Hipc). This past year, we made the following observations 1) Although there is a small change in the N-Methyl-D-Aspartate (NMDA) receptor subunit protein expression in the Hipc, this change is unlikely enough to provide such dramatic resistance to seizure activation and damage. 2) The lactating rat displayed normal behavioral responses and immediate early gene (cFos) protein expression in response to direct application of an NMDA receptor agonist into the Hipc. These results suggest that the refractoriness to neuroexcitation in the Hipc of the la ctating rat is not due to a blunting of the post-synaptic NMDA response. Therefore, the lactating rat likely has a blunted presynaptic or afferent inputs into the Hipc. One of the candidates that may be involved is neuroactive steroids (NAS). We are presently mapping the mRNA and protein expression of 3?-hydroxysteroid dehydrogenase (3?-HSD), a NAS producing enzyme, in the rat brain. We have been able to determine that Hipc displays a high level of expression of the mRNA for 3?-HSD, while it has a low level of protein expression. This may suggest that the Hipc has the potential to produce large amounts of this NAS producing enzyme under specific conditions. An understanding of the mechanisms by which suckling and progesterone interact to provide resistance to hyperexcitation and neuronal damage in the lactating rat will provide important information for the understanding of changes in epileptic seizure activity in women during different reproductive stages. FUNDING Medical Research Foundation of Oregon PUBLICATIONS Grove KL, Smith MS. N-methyl-D-aspartate (NMDA) resistance in the hippocampus of the lactating rat is not due to a lack of a functional receptor system. Brain Res 814:157-163, 1998. Grove KL, Smith MS. 3?-hydroxysteroid dehydrogenase (3?-HSD) protein and mRNA distribution in the rat brain. In Endocrine Society Program & Abstracts 80th annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 493, 1998 (abstract #P3-527). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ONTOGENY MECHANISMS
OF
IDENTIFIABLE
NEURONS
AND
OPIOID
Principal Investigator & Institution: Gintzler, Alan R. Professor; Biochemistry; Suny Downstate Medical Center 450 Clarkson Ave New York, NY 11203 Timing: Fiscal Year 2002; Project Start 01-MAY-1980; Project End 31-MAR-2007 Summary: (provided by applicant) Gestation, in laboratory animals and women, is accompanied by a hormonally activated antinociception that is predominantly driven by spinal dynorphin/K- and enkephalin/6- analgesic systems. Notably, this
Studies 73
antinociception appears not to be subject to tolerance lormation. Spinal dynorphin tone, augmented during pregnancy and its hormonal simulation (HSP), results from the offset of its negative modulation by endogenous spinal opioids and nociceptin (orphanin FQ; N/OFQ). In fact, in HSP animals, the delta-opioid inhibition of dynorphin release reverses to an enhancement. This renewal application proposes to build on these observations to elucidate mechanistic underpinnings of the antinociception of pregnancy and HSP. The organizing hypothesis is that interactions between visceral afferent input and ovarian sex steroids are causally associated with altered regulation of spinal opioid action. This results in the reciprocal feed-forward regulation of dynorphin/K and enkephalin/delta spinal opioid pathways and the ovarian steroiddependent amplification of opioid neuronal transmission. The specific objectives are to (1) Determine the influence of pregnancy and 17-betaestradiol (E2) and progesterone (P) on analgesic responsiveness to intrathecal (i.t.) delta-opioid agonists and the receptor profile thereof, (2) Determine whether or not the pregnancy profile of E2/P activates an enkephalin spinal antinociceptive system analogous to its effects on spinal dynorphin; the influence of E2/P, N-OFQ, opioids and interactions thereof on the in vitrorelease of lumbar spinal enkephalin will be investigated, (3) Determine the sequelae of sustained ovarian sex steroid treatment of orchidectomized sexually mature male rats on spinal opiold release: compare and contrast with females, (4) Determine the relevance of augmented afferent tone to the blunted formation of tolerance to endogenous opioids and the recently discovered E2/P-induced 'feed forward' opioid antinociception and (5) Determine the effect of the pregnancy profile of E2/P on opioid tolerance development to i.t. opiolds. Insights obtained from these experiments should point the way to the development of gender-based pharmacotherapies for the treatment of chronic pain (notoriously more prevalent in women than men), the usefulness of which is not restricted by the extreme loss of potency over time, the bane of narcotic utilization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASPECTS
OPIATE
ENDOCRINE
INTERACTIONS--DEVELOPMENTAL
Principal Investigator & Institution: Cicero, Theodore J. Vice Chancellor for Research; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-JUN-1985; Project End 30-NOV-2003 Summary: Description (Adapted from the applicant's abstract): The possibility that gender differences may exist in opiate pharmacology has received relatively little systematic attention despite growing, albeit often anecdotal, evidence that strong malefemale differences may exist in pain, its treatment by opiate and perhaps in abuse liability in humans. Whether these differences reflect biological or psychosocial factors has not been resolved. The purpose of this grant is to systematically determine in rats whether intrinsic, biological gender differences exist in opiate antinociception, physical dependence and tolerance and the reinforcing effects of these drugs. Accordingly, we have four specific aims: First, to examine whether there are sex differences in the pharmacological profile of morphine, including: its antinociceptive activity and its discriminative stimulus properties; the generation and expression of tolerance and physical dependence; and its reinforcing properties. Second, to examine whether the sex differences observed with morphine are a unique property of this opiate or are a more common feature of opiates selective for other opiate receptor sub-types, delta and/or kappa. Third, to determine whether the sex differences observed in opiate pharmacology can be explained by the 'activational' or organizational effects of sexsteroids. Steroids will be removed at two stages during early development - when they
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are know to exert their organizational effects on the male and female brain. In addition, adults rats will be castrated and ovariectomized to ascertain whether the acute activational effects of the sex steroids may be involved. Fourth, to examine whether the sex differences observed in opiate pharmacology can be explained solely by the metabolic or biodispositional factors rather than by intrinsic differences in the sensitivity of the nervous system to morphine. The proposed studies could be relevant to several very important clinical issues related to the abuse potential of opiates and potentially the treatment and prevention of drug abuse. Moreover, these studies could also focus on possible gender differences in the management of pain. Although there are a few studies in humans suggesting gender differences in the abuse liability of drugs, in prevention and treatment of outcomes and pain management, there have been few systematic studies examining whether these differences are related to biological factors or reflect a possible artifact related to a host of psychosocial variables. The proposed animal studies could establish whether gender differences exist and if these differences are based on inherent, first-order biological differences between the sexes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL CONTRACEPTIVES /LEIOMYOMA
/ENDOGENOUS
SEX
STEROIDS
Principal Investigator & Institution: Sweet, Stephanie; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2008 Summary: The presence of uterine leiomyomas, benign smooth muscle tumors of the uterus, has long perplexed clinicians and the patients who develop them. Their enigmatic appearance is usually silent, but in some women they can precipitate substantial symptoms that do not consistently respond to medical therapy. Leiomyomas develop almost exclusively in women during their reproductive years and their growth, seems to be influenced by endogenous sex steroids. Our hypothesis is that the addition of exogenous hormones via oral contraceptives will accelerate the growth rate of leiomyomas. This supposition is important because, to date, a key component of various medical treatments for menorrhagia caused by leiomyomas are the use of oral contraceptives. Additionally, Black women, who are believed to produce higher levels of estrogens and progestins during the menstrual cycle, have a greater propensity for developing leiomyomas. The oral contraceptives could, therefore, have an additive affect. Studies to determine the influence of leiomyoma growth by oral contraceptives have been largely speculative, conflicting, and infrequently used a case control study design. Their impact on the growth of leiomyomas in Black women, who have the largest percentage of these symptomatic tumors (3 times greater), has never been investigated. In our two-center, case-control observational study, we will directly monitor the growth of uterine leiomyomas in women using oral contraceptives by using serial ultrasound evaluations (every 6 months for 36 months). In addition, all subjects will have serum and urine assays to establish if Black women produce higher levels of sex steroids. Our deliberate effort to recruit a large number of Black subjects provides an excellent opportunity to corroborate those findings. Women selected for this study will be premenopausal and have reproducible evidence of uterine leiomyomas. The case population (n=240) will consist of women using oral contraceptives and the controls (n=80) will be women who have never used hormonal therapy. The patient base in Meharry's urban center will be an abundant resource for the inclusion of Black case subjects sufficient to detect if there truly is a racial difference in this populations' leiomyoma growth rate. This collaborative effort will be a monumental step in
Studies 75
ascertaining if oral contraceptive pills accelerate leiomyoma growth. Additionally, this will become a landmark study evaluating the seemingly exaggerated growth of leiomyomas in Black women and possibly correlating that growth difference with their increases in hormone levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PLASTICITY
OVARIAN
STEROID
HORMONES
AND
HIPPOCAMPAL
Principal Investigator & Institution: Desmond, Nancy L. Psychologist; Neurological Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 31-MAR-2005 Summary: adapted from applicant's abstract) Hippocampal function is modulated by changing levels of the ovarian steroids, estradiol and progesterone, in adult females. Of particular interest here are the observations that 1) estradiol modulates long-term potentiation (LTP) and long-term depression (LTD) of the CA3-CA1 synapses and 2) estradiol increases the excitability of CAl pyramidal neurons. We hypothesize that these two observations are not independent and that the increased neuronal excitability underlies the estradiol-dependent changes in synaptic plasticity. Thus the long-term goal of this new R01 application is to understand how changing levels of estradiol modulate the excitability of the hippocampal CA1 region and thereby the long-term synaptic modification that occurs at the CA3-CA1 synapses. Here the focus of study is the hypothesis that estradiol increases recurrent CA 1-CA 1 connectivity. Using electrophysiological and pharmacological methods in hippocampal CA1 mini-slices from adult, ovariectomized (OVX) rats pretreated with estradiol or vehicle, Aim 1 characterizes the magnitude of this changed excitability and tests hypotheses concerning the proximal causes of this enhanced excitability. Aim 2 addresses the physiological significance of this enhanced excitability using CAl mini-slices from normally cycling rats across the estrous cycle. We will also determine whether the time course of the increase in excitability across the estrous cycle correlates with the time course of the changes of synaptic plasticity (LTP and LTD) at the CA3-CA 1 synapses. Aim 3 uses morphological methods to explore the hypothesis that this estradiol-dependent increase in the excitability of CAl pyramidal neurons involves the formation of recurrent excitatory CAl-CAl synapses. We will determine if the local axonal arborizations of CAl pyramids increase with estradiol treatment of OVX rats. Aim 4 tests the hypothesis that this estradiol-dependent increase in hippocampal excitability requires the action of genomic estrogen receptors. These studies will help us to understand better how estrogens modulate the hippocampal function and thus its cognitive functions in females. Moreover, these are likely to provide important insights for understanding the biological basis of memory problems that can occur with menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OVARIAN STEROID REGULATION OF SEROTONIN NEURAL FUNCTION Principal Investigator & Institution: Bethea, Cynthia L. Senior Scientist; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001 Summary: The long-term goal of this research is to define the mechanism(s) by which progesterone (P) increases prolactin secretion in estrogen (E)-primed nonhuman primates. Prolactin secretion is a useful indicator of serotonin function and deficits in
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prolactin release are reported for patients with major clinical depression. We hypothesize that the serotonin (5HT) neural system transduces the action of ovarian steriods on prolactin secretion and mood. We showed that E and P alter the expression of 3 genes that are pivotal in serotonin neurotransmission, tryptophan hydroxylase, serotonin reuptake transporter and the serotonin 1A autoreceptor. We are now determining the functional consequences of these changes in gene expression. First, TPH protein levels were measured with Western blot and densitometric analysis in monkeys treated with E, P, E+P, modified steroids and the estrogen antagonist tamoxifen. TPH protein levels increased with E and addition of P had no further ef fect. Conjugated equine estrogens significantly increase TPH protein and addition of medroxyprogesterone acetate (MPA) blocks this effect. Hence, there is a marked difference in the action of natural progesterone and MPA on TPH protein levels. Tamoxifen significantly decreased TPH protein levels. These observations have significant implications for hormone replacement therapy and the regulation of mood in postmenopausal women and for the increased incidence of depression in breast cancer patients treated with tamoxifen. Little, if any, change was observed in the expression of 3 postsynaptic receptors for serotonin, 5HT1A, 2A or 2C, in the hypothalamus with E and P. Future studies will examine the functional consequences of the reported changes in expression of SERT and 5HT1A autoreceptor genes, as well as the effect of E+P on mechanisms regulating serotonin degradation. FUNDING NIH HD17269, HD18185 PUBLICATIONS Pecins-Thompson M, Brown NA, Bethea CL. Regulation of serotonin reuptake transporter mRNA expression by ovarian steroids in rhesus macaques. Mol Brain Res 53:120-129, 1998. Pecins-Thompson M, Bethea CL. Ovarian steroid regulation of serotonin-1A autoreceptor messenger RNA expression in the dorsal raphe of rhesus macaques. Neuroscience 89:267-277, 1998. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
OZONE
INHIBITION
OF
NEURONAL
M2
MUSCARINIC
Principal Investigator & Institution: Fryer, Allison D. Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-DEC-2004 Summary: (Adapted from the Applicant's Abstract): Exposure to ozone and to antigen causes airway hyperresponsiveness, which is due to increased release of acetylcholine from the vagus nerves. Increased release is due to dysfunction of neuronal M2 muscarinic receptors, which normally limit acetylcholine release, thus limiting bronchoconstriction. Loss of M2 receptor function and the subsequent hyperactivity is dependent upon eosinophils. Steroids are commonly used in the treatment of asthma on the assumption that they are anti-inflammatory. This proposal will address whether steroids prevent hyperreactivity by protecting neuronal M2 muscarinic receptor function. The effects of dexamethasone on hyperreactivity and M2 receptor function in vivo before and after exposure to ozone and antigen will be tested. The applicant will determine the specific mechanisms by which dexamethasone protects neuronal M2 receptor function; including whether dexamethasone inhibits eosinophil migration to nerves in the lungs by interfering with ICAM and VCAM expression. The applicant will also determine whether dexamethasone directly affects production of neuronal M2 receptors (measuring function, immunocytochemistry, M2 mRNA) in primary cultures of parasympathetic nerves. The applicant will also test whether steroids affect the activity of the human M2 receptor promoter (which the applicant has cloned). Finally the applicant will test whether dexamethasone also prevents hyperreactivity in a model
Studies 77
that does not involve M2 receptor dysfunction (3 days post ozone). It is anticipated that these studies will lead to a greater understanding of the mechanisms by which hyperreactivity occurs, and the effects of steroids in countering hyperreactivity. Since the applicant has demonstrated that the neuronal M2 receptors are dysfunctional in man following exposure to ozone, and others have demonstrated M2 receptor dysfunction in asthmatic humans, these data may be applicable to the hyperreactivity characteristic of asthma and of exposure to pollutants in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARACRINE CONTROL OF STEROIDOGENESIS BY MIS Principal Investigator & Institution: Donahoe, Patricia K. Marshall K. Bartlett Professor of Surger; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001 Summary: Mullerian inhibiting substance (MIS) is a glycoprotein hormone in the TGFbeta family of growth and differentiation factors and is required for normal development of the male reproductive tract. MIS signals through a heteromeric complex of type I and type II single transmembrane serine/theronine kinase receptors and causes regression of the Mullerian duct, which if left unfettered would lead to development of female reproductive tract structures, the Fallopian tubes, uterus and upper vagina. Expression of MIS in the newly formed Sertoli cells of the developing testis begins early (approximately 7 weeks gestation) in humans and is a hallmark of the SRY-initiated events in the fetal gonad that lead to testis differentiation. MIS is also expressed, albeit at lower levels, at adult ovaries and testes, roles for which remain unclear. However, adult transgenic mice chronically over-expressing high levels of testosterone leading to incomplete virilization. The hypothesis that MIS physiologically regulates steroidogenesis will be tested. We have cloned the rat MIS type II receptor and found that it is expressed in Mullerian ducts, in Sertoli and granulosa cells of fetal and adult gonads, as well as in adult Leydig cells, which produce testosterone in the male testis. We have also shown that the receptor is expressed in the MIS-responsive R2C cells, a transformed rat Leydig cell line and in MA-10 cells, an MIS- responsive mouse Leydig cell tumor line. These cells can now be used to great advantage to investigate the molecular signals that might be regulating the level of sex steroids. We found that recombinant human MIS causes a dramatic decline in testosterone secretion by these cells into the media and a decrease in the steady-state levels of mRNA for three key enzymes in the testosterone biosynthetic pathway, P450scc, 3betaHSD and P450c17. Further investigation with Cyp17 promoter/luciferase reporter minigenes revealed that MIS caused a marked decrease in c17 mRNA at the transcriptional level. To test the hypothesis that MIS, which is reciprocally expressed with respect to testosterone after birth, may have a physiological role in suppressing steroidogenesis, we propose to (I) define the cis-actin element and trans-acting factors involved in transcriptional regulation by MIS of the Cyp17 gene. (II) Define the type II receptor in Leydig cells during development and determine whether administration of MIS can reduce testosterone production in the adult in vivo as a prelude to considering MIS a therapeutic where reducing testosterone might be beneficial such as isosexual precocity or in prostatic carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOPHYSIOLOGY OF CUTANEOUS VASCULAR LESIONS Principal Investigator & Institution: Arbiser, Jack L. Assistant Professor; Dermatology; Emory University 1784 North Decatur Road Atlanta, GA 30322
78 Steroids
Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2003 Summary: This Career Development Award Proposal focuses on the pathogenesis of cutaneous vascular lesions. Hemangiomas are the most common cutaneous vascular lesions of childhood, and are present in 10 percent of infants at 1 year of age. These hemangiomas may grow to large size, resulting in compression of vital structures, high output cardiac failure, and coagulopathy. The coagulopathy phenomenon is known as the Kasabach- Merritt syndrome. Treatment of large hemangiomas requires lengthy treatment with steroids or alpha interferon, and surgery. A significant number of these hemangiomas do not respond to treatment, resulting in death. Little is known of the pathophysiology of these lesions, but preliminary evidence points to an imbalance of angiogenesis stimulators and inhibitors. We have developed a murine model of proliferative vascular lesions through the sequential introduction of SV40 large T antigen and H-ras into endothelial cells. This model recapitulates clinical and histologic features of both nonproliferative and proliferative hemangiomas. I wish to study the signal transduction pathways involved in upregulation of angiogenesis stimulators and downregulation of angiogenesis inhibitors. In addition, I have found that transformed endothelial cells express both VEGF and its receptor, flk-1, suggesting a possible autocrine loop. Finally, the novel angiogenesis inhibitor endostatin has been isolated from a spontaneous hemangioendothelioma cell line. Its mechanism of action is unknown. I hope to learn the signal transduction pathways through which endostatin mediates angiogenesis inhibition. Interruption of angiogenic autocrine loops and targeting of signal transduction pathways activated in proliferative vascular lesions may provide novel therapies for hemangiomas. The Folkman laboratory has extensive experience in the isolation and characterization of angiogenesis stimulators and inhibitors. In order to become an independent investigator in angiogenesis, proficiency in these techniques is necessary. The opportunity to carry out the studies outlined in this proposal and receive formal training in cell biology, protein purification and characterization, and surgical procedures will afford the applicant the training which is required toward the establishment of his career as an independent physician-scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOPHYSIOLOGY OF METABOLIC DEFECTS OF JUVENILE OBESITY Principal Investigator & Institution: Caprio, Sonia; Associate Professor of Endocrinology And; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 05-JUN-2001; Project End 31-MAY-2006 Summary: (Adapted from applicant's description): Dr. Caprio's main Patient-oriented Research (POR) focuses on the identification of early metabolic disturbances implicated in the genesis of juvenile obesity. The studies proposed here are a natural extension of her previous work in this area. She will continue to determine whether hyperinsulmemia or insulin resistance is the primary defect that is present in "high-risk" lean children of obese parents compared to "low-risk" lean children of nonobese parents. Both groups of preadolescents will be followed into adolescence to determine the evolution of putative defects in insulin secretion and action. In addition, she plans to determine if increased intramyocellular lipid stores (IMCL) of the soleus muscle are linked to the insulin resistance of childhood obesity and whether defective catecholamine-induces stimulation of lipolysis might contribute to further weight gain in obese children. 1H-NMR spectroscopy will be used to non-invasiveley assess IMCL stores and microdialysis technique to perfuse the subcutaneous adipose tissue with specific Beta1 and Beta2 andrenoceptor agonists, while simultaneously sampling
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interstitial glycerol concentrations in obese and nonobese children. Given her longstanding interest in studying hormonal and metabolic changes associated with the onset of puberty, she is determining changes in leptin levels in relation to changes in body composition, energy expenditure, LH, FSH, and sex steroids in a cohort of pubertal girls followed throughout puberty. Future directions in POR include: 1) measurement of ATP synthesis in skeletal muscle of obese subjects with known mutation in uncoupling protein 3 (UCP3) by 31P-NMR spectroscopy; 2) metabolic studies to determine the pathogenesis of type 2 diabetes in children and 3) pharmacological treatment of type 2 diabetes in youth use of Pioglitazone to reverse or improve insulin resistance. The K24 aware will not only assist her in her research endeavors, but will allow her to continue to mentor new clinical-scientists in POR. In summary, the combination of the glucose clamping tracer techniques, NMR imaging and for the first time microdialysis and NMR spectroscopy, in these studies will provide the unique opportunity to advance the understanding of the underlying pathophysiology of juvenile obesity. The long-term goal is to generate data that will lead to the development of new strategies for the prevention and treatment of juvenile obesity and Type 2 diabetes in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATTERNS OF BEHAVIORAL AND HORMONAL DEVELOPMENT Principal Investigator & Institution: Glickman, Stephen E. Professor; Psychology; University of California Berkeley Berkeley, CA 94720 Timing: Fiscal Year 2001; Project Start 01-JUN-1984; Project End 30-JUN-2002 Summary: (adapted from applicant's abstract): This research project involves the study of a very unusual animal, the spotted hyena (Crocuta crocuta), in order to understand general processes of sexual differentiation and the role of naturally circulating androgens in female mammals. Female spotted hyenas have the most highly "masculinized" genitalia of any mammalian species. There is no external vagina. The clitoris has developed until it is the approximate size and shape of the male penis and is traversed by a central urogenital canal through which the female hyena urinates, copulates and gives birth. These social carnivores live in multi-female, multi-male clans and, within these clans, adult females are very aggressive, totally dominating adult males who arrive in the clan as immigrants. Contemporary understanding of sexual differentiation requires that androgens circulate during fetal life in order to produce the "masculinized" genitalia of female spotted hyenas. Such androgens might also be expected to facilitate female aggression. In prior grant periods the investigators (1) identified ovarian androstenedione as the primary circulating androgen in female hyenas, and (2) found that it was converted by the placenta to testosterone and transferred to the fetus. This provides a route for maternal "masculinization" of her daughters, which has now appeared in the human medical literature. Four lines of research are proposed for the next grant period: (1) Experiments in which antiandrogens are supplied to pregnant females, designed to determine the maximal possible effect of such treatment on urogenital development, postnatal steroid secretion and social behavior. (2) Investigations of normal fetal urogenital development and steroid influences during the earliest stages of sexual differentiation. (3) Studies of structures/systems in the hyena Central Nervous System, which are sexually dimorphic in other species, in order to determine the extent to which such differences are attenuated, or reversed, in hyenas due to the high concentrations of pre- and post-natal androgen circulating in both sexes. (4) Studies of exogenous steroids supplied to ovariectomized female hyenas in order to determine whether the exceptional
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aggressiveness of female hyenas toward males, and the high levels of affiliative behavior observed in dominant females, is due to ovarian secretion of estradiol and/or androstenedione. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC EBM-GETTING EVIDENCE USED AT THE POINT OF CARE Principal Investigator & Institution: Davis, Robert L. Associate Professor; Pediatrics; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: The applicant plans to study the provision of evidence at the point of pediatric care, in order to increase the application of evidence- based medicine, change physician behavior, and expedite the translation of research into clinical practice. There will be two main questions. First, that use of an evidence-based decision support system at the point of care will improve antibiotic use in specific index pediatric outpatient diseases, and will (i) reduce frequency and duration of antibiotic therapy for otitis media, (ii) reduce duration of therapy for acute sinusitis, (iii) reduce use of bronchodialators in outpatient treatment of bronchiolitis, and (iv) increase use of intranasal steroids for allergic rhinitis. Second, that individualized physician feedback will provide additional benefit, when used in conjunction with the support system. This study will be carried out through a series of randomized controlled trials, implemented at three sites, including academic pediatric and family medicine health care centers, rural and suburban pediatric clinics, and a regional pediatric emergency department. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PERINATAL MECHANISMS OF DETOXIFICATION Principal Investigator & Institution: Johnson, Eric F. Professor; Scripps Research Institute 10550 N Torrey Pines Rd San Diego, CA 92037 Timing: Fiscal Year 2001; Project Start 29-SEP-1978; Project End 30-JUN-2004 Summary: (Adapted from the Investigator's Abstract) Our long-range objectives are to characterize the regulation and function of cytochrome P450 monooxygenases. These enzymes metabolize a large variety of lipid soluble xenobiotics as well as endogenous compounds such as steroids, prostaglandins, and fatty acids. The expression of individual P450 enzymes is controlled by a variety of hormonal factors, and specific P450s can be induced by xenobiotics. In many cases, the induction of these enzymes provides a means to increase the detoxication of xenobiotics or the degradation of endogenous lipids, steroids, and sterols. However, some of the ligand activated transcription factors that mediate these responses can also elicit pathological responses that lead to toxicity and carcinogenesis. These responses often vary between species, and the mechanisms leading to these negative outcomes are poorly understood. The present studies seek to delineate the mechanisms that underlie the regulation of P450 gene expression by xenobiotics and endobiotics. The specific alms focus on the regulation of family 4 P450s by ligand activated transcription factors such as the peroxisome proliferator activated receptor (PPAR), the pregnane x receptor (PXR), and other nuclear receptors. (1) Human genes that are regulated by peroxisome proliferators will be identified, and the impact of quantitative differences in PPAR expression between human and mouse will be examined to determine if this underlies the differences in the pathological effects of peroxisome proliferators observed between these species. (2) Additional human family 4 P450s will be characterized, and their potential regulation by
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nuclear receptors will be determined. (3) Mechanisms leading to the elevated expression of P450 4A4 during pregnancy, and the role of PXR or related nuclear receptors in this process, will be examined by identifying response elements and characterizing the roles of specific transcription factors in the regulation of this gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE II STUDY OF TEMOZOLOMIDE (SCH52365) PRIOR TO RADIATION THERAPY Principal Investigator & Institution: Agarwala, Sanjiv; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: This is a multinational, multicenter, open label Phase II study designed to determine the efficacy and safety of Temozolomide (SCH 52365) in the treatment of patients who have brain metastases from malignant melanoma not requiring immediate radiation therapy, previously untreated for this presentation of brain metastases, except for steroids, & who may or may not have received previous chemotherapy for the treatment of malignant melanoma. It is anticipated that 10 patients will enter this study at the University of Pittsburgh Cancer Institute. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHOTOLABELING OF ANESTHETIC STEROID BINDING SITES Principal Investigator & Institution: Evers, Alex S. Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: Certain endogenous steroids and their synthetic analogues (neuroactive steroids) produce profound and rapid effects on the central nervous system ranging from general anesthesia to seizures. While these effects are thought to result from steroid interactions with specific binding sites on the GABA-A receptor, molecular biological and biochemical studies have failed to identify candidate regions or residues that might contribute to a binding site. The overall objective of this project is to identify and characterize the binding sites for neuroactive steroids using photo-affinity labeling techniques. To achieve this goal ZCM-43, a recently developed neuroactive steroid photo-affinity labeling reagent, will be used to photo-label a 35-kDa protein in brain. There are four specific aims of this project: (1) Identify and sequence the 35-kDa protein in brain. There are four specific aims of this project: (1) Identify and sequence the 35-kDa protein using two-dimensional electrophoresis and mass spectrometry. The structural specificity of steroid interaction with the 35-kDa protein will also be examined. (2) Determine the relationship between neuroactive steroid binding to 35-kDa protein and GABA-A receptor modulation using immunoprecipitation, radioligand binding and gene "knockout" techniques. (3) Determine if GABA-A receptors or other proteins in brain also have binding sites for neuroactive steroids. These studies will be performed using novel photo-labeling reagents in which the photo-reactive group is placed in various positions on the steroid backbone. (4) Determine if neuroactive steroids compete with cholesterol for binding sites at the lipid-protein interface These studies will be performed by manipulating membrane cholesterol and examining the effects on GABA-A receptor function as well as by using a cholesterol photo-labeling reagent. The information gained from this project will provide the background knowledge and pharmacological tools to: 1) approach the question of how endogenous neurosteroids modulate CNS function in health and disease and; 2) develop new pharmaceutical
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agents including potent steroidal anesthetics with minimal side effects, novel anticonvulsants and neuroactive steroid antagonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHYSIOLOGICAL STUDIES OF NEUROSTEROID ANALOGS Principal Investigator & Institution: Zorumski, Charles F. Samuel B. Guze Professor and Chair; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2002 Summary: Neuroactive steroids and their benz[e]indene (BI) tricyclic analogues are potent and effective modulators of the gamma-aminobutyric acid A receptor-chloride channel complex (GABA A R). At low concentration, these agents augment the actions of GABA, markedly increasing responses to sub-EC 50 GABA concentrations, while having little effect on peak responses to saturating GABA concentrations. At micromolar concentrations, steroid analogues directly activate chloride channels in the absence of GABA. These effects are likely to contribute to the clinical actions of neurosteroids as anesthetics, anticonvulsants and anxiolytics. Other steroids, particularly those that are sulfated at the 3alpha-position, are negative modulators of GABAAR and alter the function of inotropic glutamate receptors (GluR). Although steroids are highly lipophilic, these agents are believed to act at specific sites on receptor proteins. Over the past funding period, a series of steroid and BI analogues were studied to examine structure-activity relationships for enhancement of GABAAR function. Included in these studies was the demonstration that steroid- and BI-mediated potentiation and direct gating of GABAAR occur enantioselectively. These studies provide strong support for the hypothesis that steroids act at specific loci on GABAAR and not via effects on membrane lipids. In the present proposal, initial studies of steroids and Bis will be extended by addressing three specific aims: 1. To gain new information about structural requirements for steroid and BI effects on GABAAR and GluR in cultured rat hippocampal neurons. These studies will conducted in collaboration with D. Covey and will examine further the enantioselctivity of steroid actions. 2. To understand mechanisms involved in neurosteroid-mediated modulation of hippocampal GABAergic and glutamatergic synaptic transmission. These studies will address whether synaptic effects of steroids and Bis are mediated primarily via postsynaptic actions and how steroids produce marked prolongation of inhibitory synaptic currents. 3. To examine factors contributing to the heterogeneity of steroid effects on GABAAR in cultured hippocampal neurons with specific emphasis on differences in GABAAR subunits expressed in excitatory and inhibitory hippocampal neurons. These studies have the potential to provide new information about neurosteroid effects in the CNS and a better understanding of mechanisms involved in steroid-induced anesthesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSTTRANSPLANT IMMUNE PARAMETERS AND DECREASED IMMUNOSUPPRESSION Principal Investigator & Institution: Matas, Arthur J. Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001 Summary: The long-term objective of our Project is to determine whether posttransplant immune parameters can predict which solid organ transplant recipients will tolerate decreased immunosuppression. The specific aims for recipients developing donor antigen-specific hyporesponsiveness. 1. To determine, in a prospective randomized trial,
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whether kidney transplant recipients can be tapered off steroids without an increased incidence of late acute rejection or of chronic rejection. 2. To determine whether heart transplant recipients can be tapered off steroids without an increased incidence of acute rejection and without an increased risk of allograft vasculopathy. 3. To determine whether lung transplant recipients can be converted from oral to inhaled steroids without an increased incidence of acute rejection episodes and without an increased risk of obliterative bronchiolitis. It is well-recognized that posttransplant immunosuppression is associated with morbidity. And many immunosuppressive care protocols attempt to lower or withdraw some immunosuppressive agents. However, trials of immunosuppression drug withdrawal or dosage lowering, based on clinical criteria alone, have not been routinely successful. We have previously shown that patients who develop donor antigen-specific hyporesponsiveness have decreased incidence of late acute rejection episodes, decreased chronic rejections (biopsy proven in kidney transplant recipients, coronary artery disease on angiogram in heart transplant recipients, and of obliterative bronchiolitis in lung transplant recipients), and improved long term graft survival. The goal of the current study is to determine whether those who have developed donor antigen-specific hyporesponsiveness can have the same excellent long-term outcome after prednisone withdrawal ( in kidneys and heart recipients) or conversion to nebulized prednisone (in lung transplant recipients). Identification of a subpopulation of patients who can safely tolerate prednisone (in long transplant recipients). Identification of a subpopulation of patient who can safely tolerate prednisone withdrawal will allow potential for decreased morbidity for these, while simultaneously not withdrawing prednisone from those who would be at risk for rejection episodes, will similarly help preserve graft function and decrease morbidity (due to the antirejection treatment). Finally, for lung transplant recipients who remain responsive to donor antigens, we will also determine if the addition of inhaled steroids to their oral steroid regimen will decrease the risk of bronciolitis obliterans. Thus, this study has the potential for allowing selective immunosuppression for transplant recipients after the first year. The selective immunosuppression will help improve graft survival while potential decreasing posttransplant morbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRE-CLINICAL STUDIES ON LUPINUS TERMIS SEEDS EXTRACT Principal Investigator & Institution: Antoun, Mikhail D. Professor and Faculty Chairperson; Pharmaceutical Sciences; University of Puerto Rico Med Sciences Medical Sciences Campus San Juan, PR 00936 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 30-NOV-2003 Summary: (provided by applicant): Atopic dermatitis is a skin condition that affects an estimated 10-20 percent of the population. Aside from Protopic (tacrolimus) ointment, which has been recently approved by the FDA, the main treatment for the past 40 years has been steroids. This proposal is intended to carry out preliminary pharmacologytoxicology studies on an alcoholic extract obtained form the seeds of a plant which, in earlier clinical studies performed outside the US, demonstrated encouraging activity in the management of chronic hand and foot eczema. The results that will be obtained will be used to develop a future R01 grant application that will include a phase II clinical trial to evaluate the extract in the treatment of chronic atopic dermatitis. The studies are intended to 1) assure the quality of the imported seeds, by analyzing different crops obtained from the source country, over a period of two years; 2) develop a standardized reproducible method for the preparation of the extract; 3) determine the stability of the ointments prepared from the extract; 4) carry out a repeat-dose toxicology study of the
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ointments, for nine months, in pigs; 5) carry out a systemic exposure of rats to the active components of the extract, for 90 days, by oral administration; 6) perform a battery of genetic toxicology studies, and 7) investigate whether the extract and ointment preparations have the potential to induce sensitization. The source material is a commercial cash crop. Experimental procedures approved by the U.S. Pharmacopeia/National Formulary, or well-established published protocols will be used in the quality assurance studies. The animals will be housed in the Animal Resources Center of the Medical Sciences Campus of the University of Puerto Rico, throughout the period of the study, under the care of the facility's veterinarian. This facility is accredited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC International) Developing a new herbal treatment for chronic atopic dermatitis will benefit patients who are at risk or who have developed resistance to other therapies, including Protopic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGESTERONE/ANDROGEN FEEDBACK CONTROL OF GNRH NEURONS Principal Investigator & Institution: Moenter, Suzanne M. Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2003; Project Start 23-APR-2003; Project End 31-MAR-2008 Summary: Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway regulating reproduction. Pulsatile release of GnRH stimulates secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from pituitary gonadotropes and is absolutely required for fertility. In female mammals, shifts in GnRH pulse frequencies help drive the preferential release of LH or FSH at specific times of the cycle to create appropriate hormone milieux for ovarian follicle maturation. GnRH pulse patterns are largely regulated by negative feedback from the ovarian steroids progesterone and estradiol. Although this feedback is well characterized in vivo, the underlying cellular mechanisms and neural pathways have yet to be elucidated. This has precluded understanding the neural components of common forms of hypothalamic infertility, such as polycystic ovarian syndrome (PCOS), in which elevated circulating androgen levels are accompanied by a persistent high frequency of LH (and presumably GnRH) release. The latter appears to be due in part to androgens interfering with the efficacy of progesterone feedback. Considerable evidence suggests one mechanism of steroid feedback regulation of GnRH release is transsynaptic. In particular, anatomical and physiological data support a role for gamma-aminobutyric acid (GABA)- and opiate peptide-producing neurons in this communication. Four Specific Aims are proposed to investigate the cellular mechanisms of progesterone feedback, and how androgens might alter the efficacy of progesterone feedback. The primary methodology will be electrophysiological recordings of green-fluorescent protein-identified GnRH neurons in acute brain slices. Aim 1 will investigate the effects of steroid and neurotransmitter milieux on the firing properties and firing patterns of GnRH neurons. Aim 2 will examine how steroids and neurotransmitters alter GABAergic drive to GnRH neurons. Aims 3 and 4 will study the effects of steroids and neurotransmitters on potassium and calcium currents, respectively, as these play major roles in setting firing properties of neurons as well as their ability to respond to synaptic input. These studies will help us understand GnRH neuron physiology in both healthy and diseased states, knowledge paramount for improving treatments for hypothalamic fertility disorders, developing novel contraceptive methods, ensuring effective
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reproduction in endangered and food-producing species, and understanding other similar neuronal systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROPHYLACTIC EFFECT OFGLUCOCORTICOIDS ON AIRWAY HYPERREACTIVITY Principal Investigator & Institution: Mcfadden, E R.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: The purpose of this study is to evaluate the dose response relationship for either a tapering dose of oral steroids or an inhaled metered dose regimen of steroids and specific stimuli in asthmatic subjects. Over the past few years, effective protocols and care paths have been developed for inpatients admitted with asthma. More recently, attention has been focused on the short and long-term follow-up of such patients discharged from the hospital and directly from the emergency room as well. Specifically, attention has turned to the high rates of relapse and return admissions with all the attendant costs in terms of added morbidity and utilization of heathcare resources. Guidelines for caring for these patients have looked to the notion that asthma represents a chronic inflammatory state in the airways and that treatment of inflammation with glucocorticoids is an essential component of management, especially after discharge. Of particular interest is the belief that a tapered dose of oral steroids or an inhaled metered-dose regimen of steroids begun upon discharge will protect the patient against future encounters with allergen or other stimuli. Although this belief is widely held by many physicians, well controlled studies adressing this issue are lacking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROSTAGLANDIN SIGNALING IN FEMALE REPRODUCTION Principal Investigator & Institution: Reese, John J. Pediatrics; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 04-MAY-2001; Project End 30-APR-2006 Summary: (Adapted from the applicant's description): Cyclooxygenase (COX)-derived PGs are implicated in many aspects of reproduction, including ovulation, implantation and parturition, yet limited information is available regarding the regulation of PG ligand-receptor signaling in the uterus. This application will provide the principal investigator (PI) with a balanced educational and research program to investigate mechanisms of PG signaling in the mouse under the mentorship of an established reproductive scientist. The proposal is supported by advisors with expertise in parturition and PG biology. Premature birth remains a perplexing clinical problem despite efforts to identify and treat the underlying causes of preterm labor. The applicant is examining parturition in the mouse to better understand the molecular basis of this process. Preliminary results show that: 1) distinct expression of COX-1 and COX2 occurs in the term uterus; 2) estrogen and progesterone receptors co-localize to the specific sites of COX-1 and COX-2 expression, respectively; 3) COX-2-derived PGs do not compensate for parturition failure in COX-1-/- mice, although exogenous PGs are effective; and 4) fetal PGs rescue parturition failure in COX-1 -/- recipient mice carrying wild-type embryos resulting from embryo transfer. Collectively, these results suggest that multiple aspects of parturition converge on the PG signaling pathway. The effects of ovarian steroids and the receptors that transduce PG signals during parturition are poorly defined. Thus, a model for parturition that encompasses these ligand and
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receptor relationships is needed. The objective of this application is to identify the cellular source of PGs and their receptors, examine the influence of ovarian steroids on their expression, and determine the contribution of fetal PGs to parturition in the mouse. The central hypothesis is that estrogen and progesterone exert significant effects on parturition by altering the levels of PG ligands or receptors, and that uterine contractility and cervical maturation during term and preterm labor are mediated by the differential actions of distinct PG receptors. The applicant will use genetic and pharmacologic approaches to: 1) examine the source and steroid regulation of PG synthesis during term or preterm labor; 2) determine the sites of PG actions during term or preterm labor; 3) quantify the contribution of fetal and placental-derived PGs to term and preterm labor; and 4) determine whether preterm labor occurs in PG-deficient mice and whether this is regulated by different pathways than in wild-type mice. The study will use COX-1-/- and cPLA2-/- mice, selective COX inhibitors, and an established method for induction of preterm labor. The results of these experiments will enhance the understanding of maternal-fetal PG signaling, and are likely to provide new insights into premature or dysfunctional labor in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROSTATIC STEROIDS AND SECOND MESSENGERS Principal Investigator & Institution: Rosner, William; Professor; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, NY 10019 Timing: Fiscal Year 2001; Project Start 11-MAR-1997; Project End 28-FEB-2002 Summary: At autopsy, 50 percent of men aged 51-60 have histologic criteria for benign prostatic hyperplasia (BPH), and this incidence increases with age. This high incidence of BPH translates into about 300,000 surgical procedures per year at a cost of over one billion dollars annually. In spite of the high cost in disability and dollars, our initimate, detailed knowledge of the causes of BPH remains inadequate. Studies of androgens, the most intensively examined group of substances in the control of prostatic growth, and estrogens have failed to explain the definitive events leading to BPH. It long has been known that the presence of testis and aging are necessary for BPH to occur. However, it is most puzzling that as the frequency of BPH goes up with age, the most important acknowledged physiologic stiumlus to prostatic growth, testosterone, falls in plasma and the concentration of its binding protein, sex hormone- binding globulin (SHBG), rises. Further, within the prostate, testosterone does not rise with age in either stroma or epithelium, while dihydrotestosteron (DHT) is constant with age in stroma and falls substantially in epithelium. Recent observations may explain these inconsistencies and open new areas of understanding and therapy. Androgens and estrogens exert their effects through intracellular receptors. Attempts to unravel the role of androgens and estrogens in BPH rely on this well-established model as a basis from which to go forward. It has been demonstrated that the prostate contains an additional signaling system for androgens and estrogens that functions through the intermediacy of a receptor (RSHBG) for plasma SHBG. Using this signalling pathway, these steroids engender rapid rises in intracellular cAMP. We have shown that the system is involved in both growth and the nonligand activation of the androgen receptor. Others have shown that cAMP is a powerful modulator of the transciptional effects of endogen and estrogen receptors; however, virtually nothing is known of how cAMP-induced modulation or transcription is physiologically regulated. The RSHBG system is an ideal candidate to be such a regulator. Our long term objective is to integrate this new steroid signaling system into the general mechanisms of steroid hormone action in the prostate. Our specific aims in this applicatin include: unraveling the mechanism of RSHBG-
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induced activation of PSA secretion in the absence of androgens, examination of the mechanisms of RSHBG modulation of estrogen and androgen- induced gene transcription, and determination of the relationships among RSHBG, cAMP response element-dependent gene transcription and prostate growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RACIAL DIFFERENCES IN CIRCULATING SEX STEROIDS Principal Investigator & Institution: Bohler, Henry; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2008 Summary: The overall hypothesis of this proposal is that elevated sex steroid levels may account for some of the hormone related conditions that follow throughout life in African American females, including leiomyomas, endocrine related cancers, and protection from osteoporosis. If so, we may then begin to understand their contribution to these processes, both protective and additive in Black females. This will form the basis for better understanding these conditions in all females, and also will allow us to amend our preventive strategies to prevent these morbidities. We propose to both quantify differences in sex steroid levels in the normal menstrual cycle, as well as to identify mechanisms. We further propose to examine the effects of sex steroids on an end organ-in this case bone mineral density and architecture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF P450C17 LYASE ACTIVITY IN ADRENACHE Principal Investigator & Institution: Dong, Qing; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Adrenarche is the peri-pubertal event that occurs when the human adrenal begins to make large amounts of 19-carbon androgen precursors, especially dehydroepiandrosterone (DHEA). Children normally begin adrenarche at about age 8-9, before the onset of puberty. Clinical studies show that early, exaggerated adrenarche may be an early sign of the polycystic ovary syndrome (PCOS), which affects 3-5% of women of reproductive age. PCOS women have increased secretion of C-19 steroids from both the adrenals and ovaries. The conversion of 17OH pregnenolone to DHEA by the 17,20 lyase activity of cytochrome P450c17 determines the amount of C-19 steroid produced in both tissues. P450c17 catalyzes both 17ahydroxylase and 17,20 lyase activities. When expressed in the zona fasciculata, P450c17 catalyzes 17(t-hydroxylase but very little 17,20 lyase activity to produce cortisol. When it is expressed in the adrenal zona reticularis and in the gonad, it has high 17,20 lyase activity and catalyzes the formation of DHEA. The ratio of hydroxylase to lyase activities is not constant, but is regulated at the post-translational level, at least in part by serine/threonine phosphorylation. Phosphorylation of P450c17 preferentially increases lyase activity. Dephosphorylation of P450c17 by protein phosphatase PP2A inhibits lyase activity without affecting 17a-hydroxylase activity. Thus, I hypothesize that the phosphorylation by protein kinase and dephosphorylation by protein phosphatase of P450c17 are two physiologically important pathways in regulating human adrenal androgen production. I propose to test this hypothesis by pursuing four specific aims. Aim 1: Identify the specific phosphorylated serine and threonine residues on P450c17 critical for 17,20 lyase activity. Aim 2: Determine whether phosphorylation of serine residues influences association with P450 oxidoreductase and/or cytochrome
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b5. Aim 3: Identify the kinase(s) responsible for P450c17 phosphorylation. Aim 4: Define the regulatory subunit(s) of phosphatase PP2A responsible for dephosphorylation of P450c17. Fulfillment of these four aims will expand our understanding of the mechanisms by which androgen production is regulated in both health and disease and should provide novel insights into the mechanisms by which the adrenals and gonads of women with PCOS overproduce androgens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF PROSTATE BLOOD FLOW BY ANDROGENS Principal Investigator & Institution: Buttyan, Ralph E. Professor; Urology; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): The prostate gland is a simple male sexual accessory tissue that requires androgenic steroids for its embryonic and postnatal development and for maintenance in the adult state. Enigmatically, this tissue is the source of several major debilitating diseases associated with human aging and these diseases are also influenced by the androgenic environment of males. In the past, it was assumed that androgen action on prostate cells was based on a direct role for these steroids in stimulating the proliferation, gene expression and survival of androgen receptor-expressing prostate cells. Significant new evidence obtained from studies of the rat model of prostate growth indicates that, at least part of androgenic control of this tissue may lie at the level of blood flow regulation and the indirect effects of androgenic steroids on the ability of the prostatic vasculature to support sufficient blood flow to the tissue. Experiments in this project will mechanistically conform the relevance of androgen's effects on prostate blood flow and vascular function in the rat model of prostate growth regulation. A variety of drugs that suppress vascular constriction will be tested to determine whether they can also suppress prostate cell apoptosis and prostatic regression following castration. As well, we will identify the vascularregulating polypeptides factors (positive and negative) produced by the adult rat prostate gland and characterize how these factors respond to androgen stimulation or withdrawal. Our characterization of this molecular response to androgen manipulation will be used to identify appropriate targets so that we can mechanistically determine whether manipulation of the functional activity of these individual molecules, in vivo, will alter the rat prostate's response to androgenic therapies. Coordinate studies of human prostate tissues obtained at acute intervals following androgen-deprivation therapy will enable us to confirm that androgenic steroids similarly affect prostate blood flow in humans. Studies of human prostate cancer xenografts (maintained in male immunodeficient mice) will enable us to determine whether androgen control of tumor blood flow is involved in prostate cancer growth/regression processes. Finally, by characterizing unique genetic differences between human endothelial cells cultured in the presence/absence of androgen-sensitive human prostate cancer cells, we will identify genetic markers of prostate/prostate cancer endothelium that might be useful for the diagnosis or development of novel therapeutics for human prostate diseases. Our work in this project will allow us to address the controversial and critical hypothesis that androgenic steroids control prostate size by regulating the flow of blood to the tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF REPRODUCTION Principal Investigator & Institution: Mellon, Synthia H. Professor; Ob, Gyn and Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-AUG-1991; Project End 30-JUN-2006 Summary: The long term objective of this project is a thorough understanding of how steroid hormone synthesis is regulated in a developmental and tissue-specific fashion, and how dysregulation may result in reproductive disorders such as polycystic ovarian syndrome (PCOS). The genes for steroidogenic enzymes are transcriptionally regulated at several levels: developmentally, tissue specifically, and hormonally. This regulation shares common features but also differs among the various genes for the steroidogenic enzymes and among various mammals. We will focus on the gene encoding P450c17 (17alpha hydroxylase/17,2 lyase) as it is the key branch point in steroidogenesis, it has been implicated in the etiology of PCOS, and it may be involved in early development of nervous and reproductive systems. Its expression in the human adrenal is required for the synthesis of 17 hydroxy C21 steroids (e.g. cortisol) and for synthesis of C19 sex steroids in the gonads and brain. In the nervous system, expression of P450c17 also results in DHEA synthesis, a potent neuromodulators. We have been using the rodent as our model system for studying the transcriptional regulation of this gene, and have identified cis-acting DNA elements and several novel trans-acting nuclear factors. One of these transcription factors, SET, had been identified from a chromosomal translocation in a patient with acute undifferentiated leukemia, but its role as a transcription factor way unknown. We shall now determine the mechanism of SET action by identifying its DNA binding, transactivation, and potential dimerization domains, and identifying co-factors that may interact with SET to participate in its transactivating functions. AS SET is abundantly expressed and regulates P450c17 expression in the developing gonad and nervous system, we will determine if these cofactors are tissue- specifically expressed, and/or if they modify other known functions of SET. Our studies localizing cis-active elements in the rat P450c17 gene have identified a region bound by a factor that we call StF-IT-2, that interacts with the orphan nuclear receptor SF-1 in a novel way, to regulate P450c17 transcription. We will characterize that interaction, and purify, characterize and clone the cDNA for StF-IT-2. Successful completion of these studies will give us a better understanding of how the gonadal and nervous systems initiate steroidogenesis, the mechanism of action of a new class of transcription factor, novel mechanisms by which SF-1 regulates gene expression, and will identify another transcription factor that may participate in a unique aspect of P450c17 expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN Principal Investigator & Institution: Clark, Barbara J. Biochem and Molecular Biology; University of Louisville University of Louisville Louisville, KY 40292 Timing: Fiscal Year 2002; Project Start 15-AUG-1996; Project End 31-MAR-2006 Summary: (provided by applicant) Steroidogenesis in the adrenal and gonads is acutely controlled by tropic hormones via regulating the synthesis of the steroidogenic acute regulatory (StAR) protein. StAR synthesis is critical for cholesterol translocation across the mitochondrial outer membrane to the inner membrane where the first enzymatic step in steroidogenesis occurs; cholesterol conversion to pregnenolone by the cholesterol
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side-chain cleavage enzyme. Mutation(s) in the StAR gene that lead to the production of a non-functional protein is the genetic basis for the disorder lipoid congenital adrenal hyperplasia (LCAH). LCAH patients have markedly impaired adrenal and gonadal steroidogenesis due to the inability to transport cholesterol into mitochondria. Thus, understanding the mechanisms that control StAR expression and function is fundamentally important. Multiple signaling pathways have been shown to regulate StAR at both the transcriptional and post-transcriptional level in a cell-specific manner. StAR transcription and protein expression, however, appear to be independently regulated by the cAMP-protein kinase a pathway. The overall objective for this research is to elucidate the molecular mechanisms for the cAMP-dependent regulation of StAR expression at the transcriptional and translational, and post-translational levels in mouse Leydig and adrenal cells. The studies outlined in this proposal will determine whether I) the cAMP-dependent increase in StAR gene activation involves both loss of repressor and gain of activator, functions, 2) the level of cAMP-dependent protein kinase A activity distinguishes StAR (acute) from CYP1 IA (chronic) gene expression, 3) protein kinase A functions at the post-transcriptional level to control StAR protein expression, and 4) StAR is translated on polysomes associated with mitochondria. Defining the specific mechanisms for cAMP-dependent StAR regulation within one cell type is important in defining the similarities and differences in tropic hormone action on adrenal, ovarin, and testicular production of steroids. This will ultimately lead to a better understanding of potential developmental or disease states that result from aberrant over- or under-expression of StAR in a cell-specific manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPRODUCTIVE ANDROGENIZATION
CONSEQUENCES
OF
PRENATAL
Principal Investigator & Institution: Padmanabhan, Vasantha; Professor of Pediatrics; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 08-AUG-2001; Project End 31-MAY-2006 Summary: Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy and it affects 10 percent of reproductive-aged women. The etiology of chronic hyperandrogenic anovulations, such as PCOS, may have genetic underpinnings. Although the underlying mechanisms are unknown, PCOS is now recognized as hyperandrogenism accompanied by anovulation. Polycystic ovarian morphology is highly correlated with conditions in which the fetus has been exposed to high amounts of sex steroids before birth. For example, women with classical 21-hydroxylase deficiency mimic PCOS, exhibit anovulation, ovarian hyperandrogenism, and LH hypersecretion. Perhaps excess sex steroids early in life may provide a hormonal "insult" that results in manifestation of PCOS later in adulthood. This proposal aims to use a new model, the prenatally-androgenized sheep (long gestation, mono-ovular species), to investigate causal mechanisms for the developmental origins of PCOS. Our preliminary studies indicate that these sheep develop ovulatory defects during adulthood similar to those of women with PCOS: anovulation, elevated LH levels, hyperandrogenemia, hyperinsulinemia, and multifollicular ovaries. In this proposal, we will test the following hypothesis: prenatal exposure to androgens disrupts adult reproductive function culminating in hyperandrogenic anovulation and that this disruption is mediated via reduced sensitivity to the positive feedback actions of estradiol, abnormal gonadotropic drive and/or altered ovarian sensitivity to FSH. The specific Aims of the proposed research are to determine 1) the extent to which fetal
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exposure to androgens disrupts reproductive cyclicity, ovarian function, ovulatory capacity and fertility in adulthood, (2) if reduced sensitivity to estradiol stimulatory feedback of gonadotropin secretion contributes to the disruptive effects of prenatalandrogenization on postnatal reproductive cyclicity, and (3) if abnormal gonadotropic drive and/or reduced ovarian sensitivity to FSH contributes to the disruptive effects of prenatal- androgenization on postnatal reproductive cyclicity. If our hyposthesis proves to be correct, this would form the basis for a distinct developmental origin of an important reproductive disease in adulthood. Specifically it will establish that discrete, experimentally induced androgen excess of fetal sheep provides the first clear etiology for hyperandrogenic anovulation in adulthood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPRODUCTIVE STEROIDS AND EXPERIMENTAL STROKE Principal Investigator & Institution: Murphy, Stephanie J. Comparative Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 15-MAY-2000; Project End 30-APR-2005 Summary: Candidate: Dr. Stephanie J. Murphy plans to establish a biomedical research career integrating neuroscience and specialization in comparative medicine with the clinical aspects of stroke. Her extensive formal doctoral training in biochemistry, clinical training in comparative medicine, and postdoctoral research in cerebral ischemia has given her a broad multidisciplinary background to achieve this goal. Environment: The A/CCM Research Division at the Johns Hopkins Medical Institutions offers exceptional personal guidance, interactive and experienced researchers, and excellent physical facilities with which to execute this research proposal. Drs. Patricia D. Hurn and Richard J. Traystman have offered their support and mentorship to Dr. Murphy. Research: We have shown that brain outcomes after experimental stroke are gender-specific and linked to reproductive hormone status. There are striking differences in post-ischemic brain injury after middle cerebral artery occlusion (MCAO) in female vs. male rat, suggesting that females enjoy substantial neuroprotection when confronted with an ischemic episode. Preliminary work suggests that reproductive steroids may reduce brain injury in older animals. The work proposed will clarify the neuroprotective importance of estrogen, alone or with progesterone, in reproductively senescent female (RSF) ischemic rat brain and assess if estrogen or combined hormone therapy alters ischemic outcome by reducing injury due to dopaminergic hyperactivity and hydroxyl radical formation. In Aim 1, we will determine if hormone replacement provides neuroprotection in RSF rats during reversible MCAO. Ischemic outcomes are determined by infarction volume analysis. Aim 2 determines if estrogen or combined hormone treatment attenuates ischemic injury by reducing dopaminergic neurotransmission utilizing microdialysis. Aim 3 determines if reproductive steroids alter infarction outcomes after MCAO in RSF rats by reducing hydroxyl radical formation from either dopamine (DA)-induced or non-DA derived sources as determined by salicylate trapping and microdialysis. In Aim 4, we will assess if ovarian steroids induce DA-modulated neuroprotection through increases in DA uptake and intracellular transport via increased expression of the DA membrane transporter (DAT) and the vesicular monoamine transporter (VMAT2), respectively. DAT and VMAT2 expression are determined using in situ hybridization, Northern blots, RNAase protection assays, immunohistochemistry, and Western blots. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RSL, A NOVEL REGULATOR OF SEXUALLY DIMORPHIC LIVER GENES Principal Investigator & Institution: Robins, Diane M. Professor; Human Genetics; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: Differences between men and women, from physiological to molecular levels, occur in systems far more diverse than those primarily involved in reproduction. A known paradigm is the sex- specific pattern of gene expression in liver for a broad array of proteins that metabolize steroids and drugs, or function in pregnancy. These distinctions in expression are induced by the sex steroids acting via the pituitary to direct a specific profile of growth hormone secretion. Although studied mostly in rodents, this regulatory axis exists also in humans, where it may impact sex differences in drug sensitivity, incidence of certain liver diseases, or complications in pregnancy. Therefore, it is critical to ascertain mechanisms in such precise tissue-specific and hormonal control. An androgen-independent control in male-specific liver gene expression is revealed by mice carrying rsl alleles (regulator of sex-limitation). Rsl is involved in regulation of the mouse sex- limited protein (Slp) gene, which is normally restricted in expression to adult male liver and kidney. In mice homozygous for rsl, Slp also is expressed in females at puberty. Slp synthesis is also increased in the rsl males, and occurs even in rsl mice lacking androgen receptor, indicating that this regulation is independent of androgen induction. We have shown that the rsl effect is liver-specific and does not act on Slp in kidney, and that it affects the array of male-specific liver genes, including P450s and mouse urinary proteins (MUPs), to cause their expression in females. The rsl variant reveals that wild type Rsl's normal function enforces dimorphic liver gene expression by negative regulation that silences male-specific genes in females. A likely mechanism is via transcriptional repression that acts on Rsl target genes in both sexes, and is overcome in males by puberal hormonal induction. The overall goal of this project is to characterize this novel tissue- and gene-specific negative regulatory pathway and to identify the Rsl gene. We will: I) Clone the Rsl gene based on its chromosomal position, which is already narrowed to a genetic interval of 1.2 cM; II) Define the molecular basis of action by identifying Slp cis-acting elements that are targets of the Rsl pathway; III) Define temporal and spatial interaction between Rsl control and hormonal induction of the target genes. Establishing the basis of the Rsl pathway will enhance our understanding of basic mechanisms of gene expression. Further, Rsl control in mice may yield unique insights into regulation of liver genes in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEASONAL PLASTICITY IN STEROID-SENSITIVE NEURAL CIRCUITS Principal Investigator & Institution: Ball, Gregory F. Professor; Psychological & Brain Sciences; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 08-AUG-1997; Project End 30-JUN-2008 Summary: (provided by applicant): Understanding brain plasticity is a major challenge facing the neurosciences. One class of animal models useful for these studies involves brain changes that occur naturally in response to salient environmental stimuli that regulate seasonal variation in reproductive physiology. Seasonal changes in the brain of songbirds are one of the most dramatic examples of this natural neuroplasticity. This
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proposal analyzes the anatomical circuits and cellular events that mediate the effects of steroid hormones on singing behavior and on the morphological plasticity of song control nuclei and investigates the possible effects of singing on brain plasticity. Aim I will determine whether steroids act directly on neurons that are active during singing (Expt 1). Aim II concerns the role of catecholamines in song production by analyzing the relationships among tyrosine hydroxylase-immunoreactive inputs to song control nuclei, immediate early gene expression (IEG) and steroid receptors (Expts 2-4). Aims III and IV will investigate steroid controls of cellular signals that are implicated in the recruitment and survival of new neurons that contribute to seasonal changes in the brain. Aim III will analyze whether steroids act directly on cells that produce Brain Derived Neurotrophic Factor (BDNF) and will investigate the effects of singing on BDNF expression in song nuclei (Expts 5-6). Exp 7 will test with antisense techniques whether singing-induced IEG expression is required for the stimulaton of BDNF production. Reelin, a glycoprotein that plays a key role in neuronal positioning during ontogeny, was recently shown to be present and regulated by testosterone (T) in song nucleus HVc in adult birds. Aim IV will explore the role of reelin in the recruitment of new neurons into HVc by determining whether reelin receptors are present in newborn HVc neurons (Expt 8), characterizing the effects of T on reelin expression (Expts 9-12) and assessing the effects on neuronal incorporation of manipulations of reelin expression (Expt 13). Aim V (expt 14) will investigate whether the seasonal dissociations between the effects of T on song and on the growth of song control nuclei can be explained by the uncoupling of the response to T of some of the cellular responses investigated in the initial phases of the project. These studies will provide an integrated view of cellular mechanisms that mediate song expression and the associated seasonal neuroplasticity and will contribute to an understanding of whether brain changes can be mediated via changes in behavioral expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONIN AND SEASONAL TERRITORIAL AGGRESSION Principal Investigator & Institution: Sperry, Todd S. Zoology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: The present proposal will investigate the role of serotonin in modulating territorial aggression in a free-living animal. Serotonin levels are inversely correlated with aggressive behavior, and they have been experimentally shown to regulate aggression. This study will expand on a large base of knowledge about the behavior and hormonal control of aggression in the song sparrow Melospiza melodia morphna. The males of this species display year-round territorial aggression in both a breeding and nonbreeding context. While superficially similar, the underlying hormonal mechanisms of the behavior are different. Gonadal steroids are more important for aggression in the breeding context while nongonadal steroids regulate nonbreeding aggression, thus, this species acts as a natural "knockout" allowing a direct comparison of serotonergic modulation under two different types of steroidal regulation. Song sparrows can be experimentally manipulated in the field, thus setting up a unique and powerful model to study the neuroendocrine control of territorial aggression in situ and in multiple ecological and hormonal contexts. This research will provide valuable new insight into the steroidal regulation of the serotonergic system. In addition, this study will advance our understanding of how the natural environment influences aggressive behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEX DIFFERENCES IN BRAIN AND BEHAVIOR DEVELOPMENT Principal Investigator & Institution: Wade, Juli S. Psychology; Michigan State University 301 Administration Bldg East Lansing, MI 48824 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The studies, focusing on sexual differentiation of the song system in zebra finches, will elucidate genes and their products important for nervous system, muscle and behavioral development. Only males sing, and the brain areas and muscles that control song are larger than in females. In many vertebrates, development of these types of dimorphisms is regulated by gonadal steroids. In zebra finches, differentiation can be altered with estrogen treatment, but recent data suggest that the forebrain song control regions differentiate independent of gonadal secretions. Therefore, a screen will be conducted for genes expressed in a sexually dimorphic pattern in the telencephalon during development of morphology and singing behavior. Then, genes/proteins regulating cytoarchitecture and/or specific functions (e.g., learning) will be investigated in more detail. Using this strategy, female-specific transcripts for neurocalcin were discovered. Experiments will clarify their role and that of calcium regulation in neural development. Other studies target the role of the estrogen-sensitive protein, brain derived neurotrophic factor (BDNF) in development of the song control nuclei and regions involved in song perception. These studies will clarify the importance of learning and the brain regions that are active during song perception in females (detailed information is already available for males), and will then test the hypothesis that BDNF modulates development of these telencephalic structures and song-related functions in both sexes. Finally, it will be determined whether mechanisms regulating development in the forebrain apply to the motor nucleus and vocal organ muscles, and whether sexual differentiation at this level is normally mediated by gonadal steroids, similar to other dimorphic model systems. The candidate for this Independent Scientist Award is an associate professor at Michigan State University, and her teaching load and service obligations are substantial. The award would provide her time to (1) enhance her training in molecular techniques (those proposed in collaboration with other scientists, and new ones useful for future experiments); (2) broaden her anatomical expertise; (3) contribute to the proposed studies more directly, which will increase the rate of progress; and (4) enhance collaborations and visibility of her growing neuroendocrine group, as well as training of students and postdocs, by establishing a seminar series with leaders in her field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEX DIFFERENCES IN INFLAMMATORY PAIN Principal Investigator & Institution: Levine, Jon D. Professor of Medicine; Oral and Maxillofacial Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 31-MAY-2003 Summary: Many inflammatory disease not only have a female preponderance, but are also associated with greater severity of pain and inflammation in females. While the mechanisms underlying sex differences in inflammatory pain are still not well understood, considerable literature suggests that sex steroids play an important role in sex differences in both pain and response to analgesics, and in the inflammatory process. Although previous literature indicates that sex steroids mediate sex differences in central nociceptive mechanisms, little is known about their effects on peripheral nociceptive and anti- nociceptive mechanisms. Sex steroid receptors are present on
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sensory neurons and the investigators' preliminary experiments show that both female and male sex steroids appear to affect the primary afferent nociceptor to modulate its response to hyperalgesic inflammatory mediators. The investigator propose to extend these finds and to elucidate the underlying mechanisms by which sex differences in hyperalgesia and anti-nociception occur. Sex steroids have also been implicated in the sex differences seen in the inflammatory mediators that produce pain in patients with inflammatory diseases. The investigators propose to test the hypotheses that: 1) sex differences in inflammation are due to differences in the sex steroids in female and male rats; 2) the effect(s) of sex steroids may differentially regulate components of the inflammatory response (blood flow, plasma extravasation, and neutrophil accumulation); and 3) the effects of sex steroids on inflammation are mediated by activity of the hypothalamo-pituitary-adrenal axis. In summary, the investigators propose to test the hypothesis that sex steroids affect inflammatory pain both by modulating the severity of the inflammatory response, and hence, the production of hyperalgesic inflammatory mediators as well as the response of primary afferent nociceptors to these mediators. Using gonadal ablation and sex steroid replacement experiments, they will evaluate the mechanisms by which female and male sex steroids contribute to the differences in peripheral nociception and anti- nociception, and the components of the inflammatory response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX DIFFERENCES IN VISCERAL PAIN: INFLUENCE OF GONADAL STEROIDS Principal Investigator & Institution: Murhpy, Anne Z.; Univ of Maryland, Baltimore Baltimore, MD Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Irritable bowel syndrome (IBS), a common gastrointestinal disorder characterized by abdominal pain and a change in bowel habits, will affect up to 20% of the general population. Epidemiological studies have established that females are 2-5x more likely to suffer from IBS in comparison to males. A defining characteristic of IBS is severe gastrointestinal pain. Surprisingly, while an extensive body of research has been conducted examining the neural mechanisms underlying visceral pain, these studies have been conducted exclusively in males. Thus, it is not known how visceroceptive information is processed within the CNS of females. Similarly, the impact of gonadal steroids on visceral pain is also not known. Behavioral studies in Aim 1 will characterize the sex differences and influence of gonadal steroids on visceral pain. Our preliminary data indicate that there are profound sex differences in the visceral motor reflex, an indicator of visceral pain following noxious colorectal distention. Our data further show that the sexually dimorphic response to noxious visceral stimulation is estrogen dependent. Anatomical studies proposed in Aim 2 will test the hypothesis that sex differences in the organization and activation of the spinoparabrachial circuit provide the anatomical substrate for the dimorphic response to noxious visceral stimulation. Studies using acute somatic stimuli have reported that morphine produces a significantly greater degree of analgesia in males versus females, and our preliminary studies indicate that morphine alleviation of visceral pain is also sexually dimorphic. Studies proposed in Aim 3 will test the hypothesis that morphine produces a significantly greater degree of analgesia in males in comparison to females in a model of visceral pain. Immunocytochemical and molecular studies proposed in Aim 4 will test the hypothesis that opioid receptor expression within the lumbosacral spinal cord is sexually dimorphic. The influence of gonadal steroids on opioid receptor expression
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will also be examined. Together, these studies will begin to elucidate the neural mechanisms underlying sex differences in visceral pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX HORMONES SLEEP AND CIRCADIAN RHYTHMICITY IN AGING Principal Investigator & Institution: Murphy, Patricia J. Associate Research Scientist; Psychiatry; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-MAR-2003 Summary: Changes in the processes controlling sleep that accompany aging result in widespread complaints of sleep disturbance in otherwise healthy older individuals. It is likely that age-related changes in many physiological systems interact to produce these sleep problems. One such system is the hypothalamic-pituitary-gonadal (HPG) axis. Gonadal steroids exhibit significant declines with age, resulting in altered negative feedback to the hypothalamus, and unregulated production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent evidence demonstrates that these alterations continue and worsen with increasing age. That changing levels of gonadal hormones affect sleep quality in aging is supported by both anecdotal and empirical evidence. For example, up to two-thirds of perimenopausal women complain of sleep problems. Further, higher LH levels are associated with awakenings from sleep, and hormone replacement therapy improves objectively-measured sleep. Although investigations of sex hormones and sleep in men are rare, lower levels of testosterone in aging men have been associated with poorer sleep quality. Indeed, the few studies that have assessed sleep complaints in the context of age-associated changes in HPG functioning strongly suggest that further investigation is needed. In addition, while changes in the circadian timing system are widely believed to contribute to sleep problems in older individuals, little is known about whether circadian patterns of sex hormone release are modified as a function of aging. The proposed research plan combines a chronobiological approach to the study of changes in the HPG axis in aging with an investigation of whether sex hormone levels are associated with age-related sleep problems. One study will assess whether there are circadian rhythms in sex hormones independent of sleep, and whether patterns of gonadal hormone release are altered with aging. The second study will examine whether the balance of sex steroids and gonadotropins differs between older individuals without sleep complaints and those with sleep maintenance insomnia. The combination of findings from these studies will clarify our understanding of how sex hormones, sleep, and circadian rhythmicity interact in aging, providing an avenue for investigating hormone replacement therapies as treatments for sleep problems in older individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEX STEROID ACTIVATION OF OPIOID CIRCUITS IN THE CNS Principal Investigator & Institution: Micevych, Paul E. Professor; Neurobiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (applicant's abstract): Our long term goal is to understand how gonadal (sex) steroids regulate G protein-coupled receptor mediated neurotransmission that underlies hormonal activation of behavior. Among the best studied steroid-responsive circuits are those in the hypothalamus that regulate the female reproductive behavior, lordosis.
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Preliminary results suggest that estrogen and progesterone have differential effects on mu-opioid receptors (MOR) and opioid receptor-like orphanin receptor (OFQR). The present proposal will examine mechanisms through which estrogen and progesterone shift the functional balance of a hypothalamic circuit from inhibition to facilitation of lordosis by sequentially activating MOR and then OFQR. Specifically, the proposed experiments will test a general hypothesis: estrogen increases transmission at MOR and progesterone attenuates the inhibitory MOR activation and increases transmission at OFQR resulting in lordosis. The proposal is divided into three specific aims. First, preliminary studies indicate estrogen acts at intracellular receptors to cause endogenous opioid release resulting in MOR activation. Because there are two estrogen receptors, ER-alpha and ER-beta, a fundamental question is which receptor mediates estrogeninduced effects. In the ER-alpha 'knock-out' (ERKO-alpha) mouse, immunocytochemistry will be used to monitor MOR activation. In situ hybridization will be used to monitor OFQR mRNA levels. These experiments will determine the role of specific estrogen receptors underlying MOR activation and OFQR expression and may provide clues about steroid regulation of opioid receptors in other circuits. Second, steroids may uncouple opioid receptors from intracellular signaling cascades altering the physiologic balance between MOR and OFQR. [35S]-GTPgS binding will be used to determine the temporal and site-specific sex steroid regulation of MOR and ORQR coupling to G proteins. This will provide a measure of functional coupling of the opioid receptors. Third, several endogenous opioid peptides activate MOR, including: enkephalins, beta-endorphin and endomorphins. Only one endogenous ligand has been described for OFQR, orphanin FQ/nociceptin, but OFQR may also have several ligands. To determine which endogenous opioids regulate lordosis, passive immunoneutralization and behavioral analysis will examine whether OFQR is only activated by orphanin FQ/nociceptin, and whether MOR is principally activated by endomorphins or other endogenous opioids. Such experiments will functionally define the interaction of steroids and opioids modulating lordosis, and demonstrate a category of analyses that compare patterns of receptor activation and behavioral output of specific circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX POSTMENOPAUSE
STEROIDS
AND
MAMMOGRAM
DENSITY
IN
THE
Principal Investigator & Institution: Greendale, Gail A. Associate Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAR-2003 Summary: (Adapted from Investigator's Abstract) Epidemiologic studies find that increased mammographic density is an independent risk factor for breast cancer and the magnitude of risk associated with mammographic density is greater than that associated with almost all other known risk factors for breast cancer. This application focuses on 3 major questions: 1) are endogenous levels of sex steroids in postmenopausal women related to mammographic density; 2) does treatment with postmenopausal estrogen and estrogen/progestin therapy increase mammographic density; and 3) do the serum levels of estrone achieved as a result of treatment with postmenopausal hormone therapy predict change in mammographic density? To address these questions, the amount of density of mammograms performed during the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial will be determined using a computer-based threshold technique. PEPI was a 3-year, randomized placebo controlled trial of conjugated equine
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estrogens (CEE) vs. CEE plus one of 3 progestin regimens, which enrolled 875 postmenopausal women aged 45-64 at baseline. Data already collected as part of PEPI that will be used in this project will include: endogenous sex steroids at baseline, PEPI treatment assignment, estrone serum levels on-treatment, and necessary covariates. The project will last 3 years and take place at 3 sites: UCLA, USC, and Bowman Gray. The specific aims are to: 1) measure the density of mammograms performed at baseline and 12 months; 2) determine whether baseline mammographic density is associated with endogenous levels of sex steroids; 3) quantify the relation between change in mammographic density and adherence to treatments; and 4) determine whether changes density are associated with serum levels of estrone achieved as a result of hormone therapy. By assessing density changes in mammograms with this computerbased method, which has been previously linked to a quantified increase in risk of breast cancer, it may be possible to assess how much of a risk-increase would be predicted by hormone use. The investigators state that this may serve as the first in a series of investigations that would allow identification of those women at higher risk of developing breast toxicity from postmenopausal supplemental hormone use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX STEROIDS AND SYNAPTIC PLASTICITY IN AGING Principal Investigator & Institution: Finch, Caleb E. Professor; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001 Summary: This project addresses steroidal influences of synaptic remodeling in the rodent brain in vivo and in vitro with cell culture models, with a focus on astrocyte genes that are regulated by estradiol (E2) and corticosterone. Little is known about how steroids modulate gene expression in relation to spontaneous and injury-induced synaptic remodelling. This information is crucial to optimizing estrogen replacement therapy (ERT) in the prevention and treatment of Alzheimer disease (AD). We emphasize the regulation of GFAP and other mRNAs in the hippocampus, a brain region that is well studied for synaptic plasticity in association with learning and memory and in response to lesioning, but hat also shows a physiological synaptic remodelling during the rat estrus cycle. The regulation of GFAP receives most attention, because of its sensitivity to sex steroids, glucocorticoids, and lesions, and because of prominent age-related increases in GFAP mRNA and protein. Other responses to lesions and steroids include genes expressed in astrocytes that mediate lipoprotein trafficking and genes expressed in neurons that encode proteins of the cytoskeleton and growth cones. As an efficient in vitro model for steroid-lesion interactions, we are studying "wounding-in-a-dish" with montypic cultures of primary astrocytes, with and without co-cultured neurons. In vivo studies with female rats examine astrocyte- and neuronexpressed genes in response to E2 treatment, perforant path lesions, and E- lesion interactions. Aging rats will be examined for select responses. To probe the basis for the protective effects of ERT in AD, we will use these models to compare the effects of Premarin and its equine estrogen constituents with those of E2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEX STEROIDS, GH AND IGF I--METABOLIC REGULATION IN PUBERTY Principal Investigator & Institution: Mauras, Nelly; Chief, Division of Endocrinology; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905
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Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: The overall purpose of this study is to characterize the neuroendocrine and metabolic effects of three anabolic hormones: sex steroids, GH, and IGF-1 specifically as they increase during human puberty and adulthood. These studies are conducted at the Nemours Children's Clinic in Jacksonville, Florida. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX-BASED DIFFERENCES IN REGULATORY T CELL RESPONSES Principal Investigator & Institution: Kosiewicz, Michele M. Assistant Professor; Microbiology and Immunology; University of Louisville University of Louisville Louisville, KY 40292 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Many autoimmune diseases are much more prevalent in women compared to men, and include multiple sclerosis, arthritis and systemic lupus erythematosus. Although the reason for this difference is not currently known, the sex hormones are likely to play a significant role. A population of naturally occurring regulatory T cells, CD4+CD25+ regulatory T cells, has recently been described that is responsible for controlling autoimmune disease in mice. Elimination of this population in mice results in severe multi-organ autoimmune diseases. A homologous population has been found in humans that appears to express similar functional properties, at least, in in vitro assays. Our preliminary results indicate that both quantitative and qualitative differences exist in the CD4+CD25+ regulatory T cell population in adult, but not pre-pubertal, female versus male mice, i.e., CD4+CD25+ regulatory T cell numbers and function are decreased in adult female mice. The central hypothesis of this grant proposal is that sex steroids mediate the gender differences in CD4+ CD25+ regulatory T cells, and through this mechanism may influence the differential expression of autoimmune disease in females versus males. The following specific aims are designed to test this hypothesis: I) Characterization of CD4+CD25+ regulatory T cells in female and male mice; 2) Analysis of sex steroid influences on CD4+CD25+ regulatory T cells; and 3) Identification of the anatomical compartment(s) responsive to sex steroids that influences CD4+CD25+ regulatory T cells. The results of these studies will provide important information that can lead to the development of novel therapies for the prevention and treatment of autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNIFICANCE OF STRESS-INDUCED HIPPOCAMPAL ATROPHY Principal Investigator & Institution: Conrad, Cheryl D. Psychology; Arizona State University P.O. Box 873503 Tempe, AZ 852873503 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Chronic stress and the adrenal steroids secreted in response to stress (e.g. cortisol, corticosterone) are associated with hippocampal atrophy in several conditions including Cushing's Syndrome, recurrent depressive disorder, and aging. Even veterans with posttraumatic stress disorder, a condition with reduced cortisol at the time of diagnosis, display reduced hippocampi, leaving open the possibility that cortisol was elevated during the period of hippocampal shrinkage. A recent study suggests that cortisol elevations contribute to hippocampal shrinkage because reducing chronically elevated cortisol in Cushing's patients reverses hippocampal atrophy. Given the breadth and significance of these cortisol-related afflictions, the long-term objective of this proposal is to understand the consequences
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and mechanisms by which chronic stress and cortisol hypersecretion cause hippocampal atrophy. Dendritic retraction of CA3 neurons in rats provides a useful model to study the effects of chronic stress and elevated corticosterone on the hippocampus. Chronic stress-induced changes in CA3 dendrites parallel the human condition by shrinking after chronic stress/corticosterone treatment and reversing when the stress subsides. Thus, the mechanisms underlying stress-induced dendritic retraction are conserved across species. The objectives of this proposal are to determine the effects of chronic stress or elevated corticosterone on mechanisms of CA3 dendritic retraction and their functional significance. To achieve this goal, this proposal has three specific aims. First, to determine whether chronic stress-induced CA3 dendritic retraction is indicative of neuronal degeneration or a protective response. Second, to ascertain the levels of corticosterone that are sufficient to cause CA3 dendritic retraction and memory impairment. Third, to determine whether psychosocial stress produces CA3 dendritic retraction and to reveal the components of hippocampal-dependent memory (such as acquisition, consolidation, retrieval) that are disrupted. In all studies, corticosterone, corticosterone binding globulin, and dehydroepiandrosterone will be measured to determine whether other components of the hypothalamic-pituitary-adrenal axis are disrupted by chronic stress and whether they correlate with CA3 dendritic retraction and memory deficits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP IN OLDER WOMEN--EFFECTS OF ESTROGEN Principal Investigator & Institution: Moe, Karen E. Psychiatry and Behavioral Scis; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-OCT-2003 Summary: (adapted from investigator's abstract): Sleep complaints increase significantly with age in both men and women, but the increase is especially striking in women. Older women experience more nighttime awakenings, longer sleep onset latencies, and "lighter" sleep. Insomnia, disrupted sleep, and consequent daytime drowsiness are associated with an increased risk of accidents, increased utilization of health care and sedative-hypnotic medications, and a reduced quality of life. Older women receive a disproportionate number of prescriptions for sedative-hypnotics, which can exacerbate sleep apnea and lead to daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be agerelated changes in sex steroids such as estrogen. The very low levels of estrogen that occur post-menopause have wide-ranging chronic effects, from increased cardiovascular risk factors to possible effects on memory. Sleep changes in older women may also be related to this dramatic change in hormonal milieu. Several studies have shown that ERT can improve the sleep of peri-menopausal women, and our preliminary data shows that the use of ERT is associated with better sleep in older post-menopausal women. Estrogen acts on several brain areas important for sleep and circadian rhythms (e.g., the suprachiasmatic nucleus, the hypothalamic pre-optic area, and the pineal gland). Previous studies of ERT effects on sleep were based on peri-menopausal women who were experiencing hot flashes and/or other menopausal symptoms including depression. All but a few of these studies were based on brief subjective sleep ratings. No published studies have examined the effect of ERT on the sleep of post-menopausal women., i.e., women who are several years past menopause, menopausal symptoms, and menopause-related hormone fluctuations. The proposed study will employ laboratory-based polysomnography and a randomized, placebo-controlled within-
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subjects design to assess the effect of six months ERT or placebo on the sleep and circadian rhythms of post-menopausal women. The results will help determine the role of age-related estrogen decline in the decreased sleep quality of older women. This study is the first step in a research program investigating the relationship between sex steroids and sleep in older individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMITH-LEMLI-OPITZ SYNDROME STEROIDOGENESIS Principal Investigator & Institution: Shackleton, Cedric H.; Children's Hospital & Res Ctr at Oakland Research Center at Oakland Oakland, CA 94609 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2003 Summary: (Adapted from the applicant's Description) Smith-Lemli-Opitz syndrome (SLOS) is a devastating birth defect associated with mental retardation and multiple physical malformations. Since it is an enzymatic disorder of cholesterol synthesis (7dehydrocholesterol-7-reductase deficiency) it is likely that steroid hormone synthesis by the adrenal glands and gonads is impacted because all such compounds utilize cholesterol as precursor. SLOS patients may have quantitatively compromised steroid synthesis because of cholesterol deficiency, and in addition novel steroids with unknown pharmacological properties may be produced which retain ring B unsaturation. This application addresses such issues through a study of serum and urinary steroids. About 30 patients are routinely studied for short periods at the NIH and these will be the subjects of the study. The investigators have evidence that 7dehydrocholesterol overproduced in the disorder can act as precursor for novel C21, C19, and C18 steroids that are produced in adrenals and gonads. Once confirmed structures of urinary metabolites of such compounds have been obtained, it will be possible to state which (if not all) steroid biosynthetic enzymes accept 7- and 8dehydrocholesterol as precursor. Information on specific steroids produced in SLOS will permit easy diagnosis, maybe leading to future pre- and postnatal screening. Furthermore, is the quantitative production of steroid hormone metabolites reduced in SLOS? If so, does this suggest adrenal insufficiency? The investigators will measure 40 steroid metabolites in urine and relate their excretions to those of age matched controls and to serum hormone measurements obtained in a separate study. In addition, cholesterol is routinely given to SLOS patients for beneficial effect on behavior and growth. Does the cholesterol partially work through the adrenal steroid mechanism by contributing to hormonal synthesis? The investigators will measure steroid hormone metabolites before and after cholesterol administration and determine if there has been a measurable increase in hormonal metabolites concomitant with decreased dehydrometabolite excretion. Finally, if ring B dehydrosteroids are produced, is the ratio of the individual dehydrometabolites to corresponding conventional metabolites related to the dehydrocholesterol to cholesterol ratio and clinical severity? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPORTS, GENDER AND ADOLESCENT SUBSTANCE USE Principal Investigator & Institution: Barnes, Grace M. Senior Research Scientist; None; State University of New York at Buffalo 402 Crofts Hall Buffalo, NY 14260 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Recent research findings have shown strong associations between participation in sports and reduced sexual risk-taking, especially among adolescent girls. The present R21 application will extend this research to explore the effects of
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sports and other extracurricular activities on substance use and other risky behaviors among female and male adolescents. Cost-effective, secondary data analysis is proposed using two large data sets. The Family and Adolescent Study, a six-year longitudinal study of Western New York adolescents and their families (N=699), includes self-report data on alcohol, tobacco, marijuana and other substance use, sexual activity, and a variety of delinquent behaviors, as well as questions regarding recent participation in extracurricular activities. The 1997 school-based Youth Risk Behavior Survey (YRBS), generated by the Centers for Disease Control and Prevention, is a nationally representative cross-sectional survey of priority health-risk behaviors in American high school students (N=l 6,262). The YRBS includes data on tobacco, alcohol, marijuana, steroids, and other illicit drug use, sexual activity, and behaviors resulting in unintentional and intentional injuries (e.g., drunk driving, fighting, weapons carrying), as well as questions on athletic participation. Both sources of data oversample racial/ethnic minority populations, facilitating race-specific analysis. Specific aims of the study include determination of the nature of the relationships between sports and other specific extracurricular activities and substance use and other risky adolescent behaviors. Gender and racial/ethnic differences in these relationships will be determined. This research will also serve as a basis for the development of a theorydriven R01 proposal examining factors associated with gender-specific sports participation and substance use. This research has the overall aim of establishing more effective prevention and intervention strategies for reducing adolescent substance use and other related risk behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROID ACTION IN A VOCAL CONTROL CIRCUIT Principal Investigator & Institution: Auger, Catherine J. Psychology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: Sex steroid hormones, such as testosterone (T) and 17beta-estradiol (E2) are well known to regulate both behavior and physiology. Many of these effects require that the steroids act on the brain by finding to their steroid receptor proteins that are distributed throughout the brain. An important unanswered question facing the field of neuroendocrinology concerns how steroid action is coordinated at multiple levels. The vocal control system of songbirds is an excellent model system for such components of this circuit that are important in the motor output of song. These include telencephalic nucleic, brainstem nuclei, and the vocal production organ the syrinx. The telencephalic nuclei exhibit a hierarchal organization of motor controls. It is not known if gonadal hormones must act in all these individual nuclei and/or muscle groups simultaneously to produce the full complement of song and whether steroids have independent effects in these different structures. I will investigate steroid action in the song circuit with the selective administration of steroid receptor antagonists centrally and peripherally. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STEROID CATECHOLAMINE SYSTEMS
AND
COCAINE
INTERACTIONS
WITH
Principal Investigator & Institution: Quinones-Jenab, Vanya; Hunter College 695 Park Ave New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002
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Summary: Addiction is a complex disease which combines psychological and physiological adaptations that result in social consequences. Drug dependence gradually develops by neuronal adaptations caused by repeated exposure to the abused drug. It is critical to understand the temporal components of adaptations that occur at the neuronal circuits in the presence of a drug which, in turn, alter the CNS to a dependent state. Functional interactions between estrogen, progesterone, and the catecholamine systems may play critical roles in cocaine's reinforcing actions and behavioral alterations including locomotor and stereotypic behaviors. The identification of the roles of steroid hormones in cocaine- induced CNS alterations are behavioral and molecular levels is essential for understanding sex differences in drug abuse. The following Specific Aims are propose: (1) To utilize SCORE funding to establish myself as an independent and productive scientist in the field of neuroscience. By the termination of the funding period of this proposal, I expect to apply and obtain an independent award. This aim will be accomplished by learning new and relevant techniques, such as HPLC analysis (through the collaboration with senior members, Drs. Luine and Harding, of the Behavioral Neuroscience Group of SCORE at Hunter). Our laboratory will be more competitive by expanding the current research to neurochemical studies, an area of cocaine and steroids which differentially affect behavioral responses to cocaine. Effects of cocaine alone and in combination with hormones will be assessed on behavioral sensitization (3) To test the hypothesis that there are interactions between cocaine and steroids which differentially affects basal extracellular dopamine, serotonin, and norepinephrine concentration in the nucleus accumbens and raphe nucleus which may be the basis for sex differences in sensitization and behavioral responses to cocaine. Extracellular monoamine concentrations will be measured by quantitative microdialysis and correlated with locomoter and stereotypic activity. (4) To test the hypothesis that there are interactions between cocaine and steroids with affects the levels of mRNA and number of dopamine and serotonin receptors and transporter in the mesocorticolimbic and nigrostriatal pathways. Receptor and transporter sites will be measured by quantitative autoradiography. mRNA levels will be measured by RT-PCR and in situ hybridization and will be correlated with locomoter activity and stereotypic behaviors. The identification of which of the cocaine- induced CNS alterations at the behavioral, neurochemical and molecular levels are affected by ovarian hormones is essential for understanding the mechanism affecting sex differences. Furthermore, the correlation of behavioral endpoints (such as stereotype and locomotive activity) and neurotransmitter levels in conjunction with molecular endpoints (dopamine and serotonin transporters or receptors mRNA levels) should provide some insight into the functional significance of alterations in the CNS to cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROID AND MONOAMINE EFFECTS ON SEX, STRESS & SEIZURES Principal Investigator & Institution: Renner, Kenneth J.; University of South Dakota 414 E Clark St Vermillion, SD 57069 Timing: Fiscal Year 2001 Summary: (Adapted from the applicant's abstract): Stress responses which, when uncontrolled, can result in psychological and physiological dysfunction, are believed to involve interactions between the hypothalamus-pituitary- adrenal (HPA) axis and the hypothalamus-pituitary-gonadal (HPG) axis. The long term goals of this project are to understand the steroid-induced neurochemical mechanisms that regulate the expression of behaviors such as sexual receptivity and stress responses or pathological conditions
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such as seizures. The steroid hormones, progesterone and corticosterone, alter serotonergic activity in a number of brain regions. Progesterone effects on serotonin are linked to the control of female sexual behavior while corticosterone effects on serotonergic activity are implicated in the stress response. Preliminary results suggest progesterone and corticosterone act synergistically to markedly potentiate serotonin release in the central nucleus of the amygdala. The synergism between the two steroids on serotonin in the central nucleus of the amygdala may provide a mechanism for stress modification of female sexual receptivity. The proposed studies are designed to: 1) further characterize the synergistic steroid effects on serotonin release; 2) establish the potential physiological role of synergistic steroids effects on serotonin release in the central nucleus of the amygdala; and 3) explore the possibility that the synergistic effects of progesterone and corticosterone on serotonin release may be mediated through effects of the steroids on GABA. In addition, because of evidence linking steroid effects in the amygdala and seizure activity, studies will examine the relation between steroid enhanced serotonin release and seizure induction. The studies will be conducted in rats using in vivo micro dialysis to provide simultaneous evaluation of neurochemical and behavioral outcomes of steroid treatments and pharmacological interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROID EFFECTS IN PEDIATRIC ALL PATIENTS Principal Investigator & Institution: Soliday, Elizabeth A. Psychology; Washington State University 423 Neill Hall Pullman, WA 99164 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2003 Summary: (provided by applicant): Clinicians and families generally acknowledge the tremendous impact that high-dose steroid therapy can have on pediatric cancer patients' quality of life, yet only four studies on the psychological/behavioral effects of steroids in pediatric cancer patients have been published in the past 30 years. The objectives of this pilot study are to: a) identify areas of intervention need by assessing the frequency and severity of steroid-related changes in children's behavior, cognition, and diseaserelated psychosocial adjustment; b) examine how specific risk and resistance variables predict children's behavior and quality of life during steroid administration; c) explore relationships between steroids' effects and adherence. This will be the first theoretically based, prospective, longitudinal, repeated measures study of the psychosocial and neurocognitive effects of steroids. Guided by a stress and resistance framework and previous research, the pre-treatment baseline assessment of predictors could lead to early identification of and intervention with children at risk for adverse responses. It will also be the first study to control for maturation and test sensitivity by including a healthy sibling comparison group. In the early post-diagnosis period before remission induction treatment, children's primary caregivers will complete baseline measures of their own psychological functioning, family functioning, their children's behavior and health-related quality of life; children will complete neuropsychological measures of memory and attention. Assessments will be repeated on day ten of induction and twice during consolidation. Healthy siblings will be assessed at the same time points. Compared to healthy sibling controls, it is expected that children with ALL will experience greater adjustment difficulties during steroid administration. It is also expected that a physician rating of less severe disease status/better prognosis, older child age, male sex, and more positive family functioning will predict more positive psychosocial (behavior and quality of life) outcomes during steroid administration. Repeated measures analyses of variance will be used to test effects of treatment period (baseline, 3 steroid periods) and group status (ALL, healthy sibling) on dependent
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measures. Multiple regression models will be used to test predictive effects of stress and resistance factors on children's functioning during steroid dosing. Correlations will be used to test relationships between steroid effects and adherence. This study will contribute to the knowledge of steroids' effects and the predictors thereof so that prophylactic interventions to improve quality of life can be advanced. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROID POTENTIATION OF AGGRESSION-RELATED LEARNING Principal Investigator & Institution: Farrell, William J. Psychology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, TX 78712 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Aggressive behavior and violence impact both the health of individuals and American society. Aggressive behavior is highly plastic. Circulating steroids modulate aggressive behavior, as do learning processes such as reinforcement and associative learning. The proposed research is intended to integrate aggression-related learning into the field of behavioral neuroendocrinology. It is my hypothesis that surges in testosterone (T) following aggressive interactions render engaging in aggressive behavior reinforcing, and that corticosterone (CORT) released during aggression facilitates associative learning. The model organism will be the green anole lizard (Anolis carolinensis). A conditioned place preference paradigm will be used to determine whether engaging in aggression is reinforcing. Pharmacological and physiological manipulations of testosterone will then be undertaken to determine whether T surges are responsible for this reinforcement. Classical conditioning of aggressive behavior will then be used in conjunction with pharmacological manipulations of CORT to determine whether this hormone enhances aggressionrelated associative learning. The results of these studies will provide new information about the ways in which experience and hormones can interact to influence aggressive behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STEROID REGULATION OF DROSOPHILA PROGRAMMED CELL DEATH Principal Investigator & Institution: Baehrecke, Eric H. Associate Professor; None; University of Md Biotechnology Institute Baltimore, MD 212023101 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Steroid hormones regulate diverse metabolic, reproductive, and developmental processes throughout eukaryotes, and play an important role in human health. Relatively little is known about how steroids induce cell-specific biological responses, even though we know extensive details about how steroids activate gene transcription. We are utilizing the fruit fly, Drosophila melanogaster, as a system to study steroid-activated programmed cell death. Pulses of the steroid 20hydoxyecdysone (ecdysone) trigger genetic regulatory hierarchies that mediate the destruction of the larval tissues by programmed cell death during metamorphosis of Drosophila from a larva to an adult. We have made progress toward understanding the mechanisms underlying steroid- regulated programmed cell death, by characterizing the relationship of genes that function in steroid-activated destruction of larval tissues. Our studies have emphasized the relationship between the ecdysone- regulated E93 gene, and the programmed cell death genes rpr and hid. E93 is unique compared to previously isolated ecdysone-regulated genes - E93 is specifically expressed in cells that
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are fated to die, while other early genes respond to each pulse of ecdysone in most cell types. In addition, E93 expression immediately precedes transcription of the programmed cell death genes rpr and hid. Most significantly, ectopic expression of E93 is sufficient to induce programmed cell death, and animals lacking E93 function have larval salivary glands that fail to die. Thus, E93 may be the primary stage- and tissuespecific mediator of steroid-regulated programmed cell death during Drosophila development. Here we propose: (1) detailed characterization of E93 mutants, (2) determination of the relationship between E93 and previously identified genes that function in cell death, and (3) isolation and characterization of targets of E93 that function in programmed cell death. These studies will lead to a better under- standing of this novel cell death pathway, and how steroids activate programmed cell death in higher eukaryotes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROID RESPONSIVE MECHANISMS IN THE EAR Principal Investigator & Institution: Trune, Dennis R. Professor; Otolaryngology Head & Neck Surgery; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 22-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Although glucocorticoids, such as prednisone, have been employed for decades for control of hearing loss, little is known of the cellular mechanisms of the ear that are under their control. A better understanding of these steroid responsive mechanisms is criticai for our design of appropriate therapy. Therefore, the long term goal of this research is to characterize the steroid driven cellular mechanisms of the ear. Preliminary studies have shown hearing loss in the MRL/MpJ-Fas(lpr) autoimmune mouse responds to treatment with both the glucocorticoid prednisolone and the mineralocorticoid aldosterone. It is hypothesized that two steroid responsive mechanisms exist in the ear: a direct sodium transport effect in the stria vascularis mediated by the mineralocorticoid receptor, and an indirect systemic immune suppression mechanism mediated by the glucocorticoid receptor. The planned studies will characterize these steroid driven processes with steroid treatments that will selectively isolate and measure the cellular and molecular events they control. The specific aims to investigate these steroid mechanisms of the ear are:Aim 1: Establish the lowest effective dose of the mineralocorticoid and glucocorticoid for control of inner ear function and systemic autoimmune disease.Aim 2: Determine the lowest combination dose of the two steroids that can effectively control the inner ear dysfunction and systemic autoimmune disease.Aim 3: Determine which steroid receptor is mediating steroid control of cochlear function.Aim 4: Determine if the middle ear route of steroid delivery is a feasible treatment for either steroid control of autoimmune hearing loss.In all studies, assessment will be made of steroid effects on inner ear structure (light and electron microscopy), function (ABR, EP), cochlear specific antibodies (ELISA), and upregulated gene products (ELISA). The results from these studies will provide significant new findings regarding the cellular and molecular mechanisms of the ear that are under the control of steroids. This study also will lay important groundwork for the development of alternative steroid therapies that may be more effective than those currently employed for clinical hearing loss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STEROID-MEDIATED DIFFERENTATION OF THE PERINATAL POA Principal Investigator & Institution: Amateau, Stuart K. Physiology; University of Maryland Balt Prof School Baltimore, MD 21201
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Timing: Fiscal Year 2001; Project Start 16-APR-2001 Summary: (provided by applicant): Men and women suffer disproportionally from specific neurological and psychiatric disorders and the basis for this difference remains unclear. However, given that males and females are exposed to different levels of steroids throughout development, a role for these hormones in the etiology of sexually dimorphic neurological disorders is strongly suggested. Investigating the consequences of this dimorphic exposure will help elucidate the mechanisms of steroid action on the developing brain. Previous research in our laboratory implicates astrocytes as an important target of steroid hormone action in select regions of the developing perinatal rodent brain. The preoptic area (POA) is a major brain region controlling sex-typic behavior and physiology, and preliminary data suggest that astrocytes of this region are also responsive to steroids. We have found that as early as the day of birth, the morphology of astrocytes of the POA are sexually dimorphic. The importance of astrocytes in the establishment of neuronal architecture is becoming increasingly evident. The goal of this proposal is to elucidate the mechanism(s) of steroid-mediated changes in POA neuronal morphology involving neighboring steroid-sensitive astrocytes. Hormonal manipulation experiments will establish the steroid specificity determining neuron differentiation within the developing POA. To begin to determine the functional relationship between the two cell types, experiments will identify the components of an astrocyte-to-neuron communication cascade and examine the effect of steroid manipulation on this system. Pharmacological manipulations and the use of antisense oligodeoxynucleotides will explore the roles of prostaglandin E2 and the activation of their cognate receptors in this signal transduction mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROIDOGENIC ACUTE REGULATORY PROTEIN'S ROLE IN LIBIDO Principal Investigator & Institution: King, Steven R. Center on Aging; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Loss of libido is a significant medical problem and results in a profound diminution of life and many patient visits to the urologist. In part, male sexual drive requires the synthesis of testosterone mediated by the steroidogenic acute regulatory (StAR) protein in testicular Leydig cells. Interestingly, the enzymes responsible for steroidogenesis in the Leydig cell are also present in neuronal and glial cell types of the brain. This leads to the intriguing possibility that steroids locally produced in the brain (neurosteroids) could be involved in the regulation of libido, as well. In fact, administration of neurosteroids in the brain has been shown to affect sexual behavior in rodents. Therefore, we plan to investigate whether hormone-regulated neurosteroids are critical for libido. Recently, mRNA encoding the hormone-regulated StAR protein, was detected in the brain. This gives us an exciting chance to more directly assess the functional role of neurosteroids by developing a model whereby we eliminate StAR protein expression and thus, steroid production in the brain, without affecting steroid synthesis in the gonads and the adrenal gland. Selectivity will be accomplished by using a Cre-lox tissue-specific knockout strategy. We propose to use this model to test the hypothesis that while gonadal steroids are permissive, StARdependent neurosteroid synthesis in the brain has an essential physiologic role in libido. Therefore, to test the hypothesis that StAR-mediated neurosteroid synthesis is essential for libido, I propose to both define the pathways involved in neurosteroid biosynthesis in the brain (especially in structures important for libido) and the regulation of StAR by
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immunohistochemisry, in vitro assays, and other biochemical techniques, and to generate a conditional StAR-knockout mouse model to examine effects on the brain and sexual behavior during and after development and in aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROIDS AND STEM CELL IN CARCINOGENESIS Principal Investigator & Institution: Benbrook, Doris M. Associate Professor and Director of Rese; Obstetrics and Gynecology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, OK 73126 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Organotypic cultures are tissue culture models that mimic in vivo tissue architecture through manipulation of epithelial and stromal cells within and on top of an extracellular matrix. These models incorporate aspects of cellmatrix and epithelial-stromal interactions that cannot be evaluated in monolayer cultures. They can be used to evaluate monoclonal colonies, whereas individual xenograft tumors in animals are established from millions of cells. Colonies in organotypic culture therefore, more accurately mimic tumorigenesis than animal xenografts. Organotypic cultures can be more readily genetically and chemically manipulated than animal models, allowing increased numbers of experiments and less cost. They cannot replace animal models however, because they do not incorporate metabolic, physiologic and immunologic effects. Thus organotypic cultures can potentially be used to screen and improve chemoprevention agents prior to testing in animal models. In addition, they provide opportunities to evaluated hypothesis driven research on carcinogenesis and chemoprevention. We developed organotypic models of normal human endometrium, benign human ovarian tissue, and human borderline ovarian tumors of low malignant potential (LMP). The objective of this project is to further develop these organotypic models into models of carcinogenesis that can be used to study the processes of carcinogenesis and chemoprevention. The experiments proposed will evaluate the interaction of aromatic hydrocarbons, estrogen, progesterone, tamoxifen, differentiation and adult stem cells in endometrial and ovarian carcinogenesis. Our future goals will be to validate these models and to use them in our efforts to develop low-toxicity retinoids, heteroarotinoids, for chemoprevention. This research will enhance our understanding of the process of carcinogenesis and chemoprevention, which could ultimately translate into strategies and pharmaceuticals for prevention of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STEROIDS--FUNCTIONAL MODULATORS OF AMINO ACID RECEPTORS Principal Investigator & Institution: Farb, David H. Professor and Chairman; Pharmacol & Exper Therapeutics; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 01-JUN-1992; Project End 30-JUN-2002 Summary: (Adapted from applicant's abstract): Steroids are synthesized in the CNS, exert profound modulatory effects of receptors for amino acid neurotransmitters, and may act as endogenous modulators of synaptic activity. Abnormal activation of amino acid receptors has been proposed to play a role in the etiology of a variety of psychiatric disorders such as anxiety, depression, and schizophrenia, and to contribute to neuronal damage associated with stroke, seizures, neuropathic pain, trauma, and
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neurodegenerative disease (such as Parkinson's and Alzheimer's). In following up our original discovery that pregnenolone sulfate (PS), an abundant neurosteroid, modulates glutamate receptors, we have identified a variety of steroids that can potentiate (by up to 10-fold) or inhibit glutamate receptor function and exacerbate or protect against NMDA-induced death of hippocampal neurons in culture. One inhibitor compound, pregnanolone hemisuccinate, works in vivo to reduce middle cerebral artery occlusioninduced degeneration of cortical and subcortical nervous tissue. A major objective of this project will be to test our working hypothesis that steroids interact with the extracellular domain of individual receptor subunits and exert their effects by regulating the balance between excitation and inhibition between CNS neurons. Toward this end, novel steroids will be synthesized and evaluated electrophysiologically (using wholecell and two-electrode voltage clamp) to test specific structure-activity hypotheses and to evaluate the modulatory effects of steroids on native glutamate receptors in primary rat hippocampal neurons and on homomeric receptors expressed in Xenopus oocytes. Initial results that steroids can discriminate among glutamate receptor subtypes will be extended to search for more highly selective compounds. The effects of steroids on receptor chimeras and on receptors with single amino acid substitutions will be examined to identify specific amino acids essential for ligand recognition. Novel steroids will be evaluated for their ability to inhibit EAA-induced increases in cytosolic free [Ca2+] (using Fluo-3 fluorescence as an indicator) and excitotoxic neuronal death. Collectively these experiments will add to our understanding of the molecular mechanisms whereby steroids modulate EAAR function, and to the development of neuroprotective agents and cognitive enhancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND ACTION OF STEROIDOGENIC REGULATORY PROTEIN Principal Investigator & Institution: Bose, Himangshu S. Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 15-MAR-2000; Project End 31-DEC-2002 Summary: (taken from the application) Steroid hormones are ubiquitous regulators of physiologic process that are mandatory for the survival of the individual and the propagation of the species. The first, rate limiting and hormonally regulated step in the biosynthesis of all steroid hormones is the conversion of cholesterol to pregnenolone by the mitochondrial cytochrome P450scc system. P450scc activity is regulated chronically by the tissue-specific and hormonally regulated transcription of the P450scc gene. However, the acute, rapid, regulation of steroidogenesis, which occurs in 10-15 minutes as in the stress responses, is regulated at the level of cholesterol entry into mitochondria. This cholesterol flow is regulated by the Steroidogenic Acute Regulatory protein (StAR). StAR is found in all steroidogenic tissues that exhibit an acute response, and StAR mutations cause potentially lethal congenital lipoid adrenal hyperplasia. However, some tissues that make steroids (placenta, brain) lack StAR, and the mechanism of StAR's action is unknown. This StAR-independent steroidogenesis may be associated with MLN64, a ubiquitously expressed protein that is structurally related to StAR. The present project will expand our knowledge of the structure and function of StAR and MLN64 through five aims 1) Establish an in vitro assay for the cholesterol-transport activity of StAR and MLN-64, 2) Adapt our established procedure for the bacterial expression and purification of N-62 homologue of StAR to the StAR-like domain of MLN-64, N234 MLN-64 3) Characterize the folding of N-234 MLN-64 by circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), and fluorescence
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spectroscopy, 4) Compare the dynamics and folding of N-62 StAR and N-234 MLN-64 by deuterium exchange mass spectrometry, and 5) Determine the structure of N234 MLN-64 by multidimensional high resolution nuclear magnetic resonance (NMR) spectroscopy. Fulfilling these aims will provide the structural information needed to develop a detailed understanding of how StAR and MLN64 regulate cholesterol movement from the outer to inner mitochondrial membrane. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE/ACTIVITY STUDIES OF NEUROSTEROID ANALOGS Principal Investigator & Institution: Covey, Douglas F.; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001 Summary: Anesthetic steroids have been shown to act at the GABAa receptor/chloride channel complex to facilitate hyperpolarization of GABAergic neurons. It is currently thought that this interaction is the molecular mechanism of action of anesthetic steroids. Modulatory effects of anesthetic and other neuroactive steroids at additional ion channels are also known. The extent to which the actions of anesthetic steroids at these additional ion channels contributes to steroid-induced anesthesia is not yet clear. The specific aims of this proposal are focused on gaining new knowledge of the molecular details of the interactions of these steroids with the GABAA receptor complex and other ion channels. Synthetic chemistry will be performed to prepare novel steroid analogues and enantiomers of neuroactive steroids. Structure-activity relationships for GABAA receptor modulation will be analyzed using the computational method of Conformational Molecular Field Analysis. The steroid enantiomers will be used to distinguish between receptor-mediated effects and membrane perturbation effects. These compounds will be evaluated using electrophysiological, binding, and behavioral assays. Neuroactive steroids that increase GABA-mediated chloride current are known to have anesthetic, anticonvulsant, anxiolytic, and sedative hypnotic effects. The extent to which actions at other ion channels and/or to which membrane perturbing effects by these compounds contributes to the pharmacologic profile of neuroactive steroids is uncertain. The long term goals of this project are to use the methods of medicinal chemistry to obtain new pharmacological tools to investigate the effects of neuroactive steroids at GABAA receptors and other types of ion channels. Ultimately, this information could lead to the discovery of new anesthetic, anticonvulsant, anxiolytic, and sedative hypnotic drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNTHESIS & EVALUATION OF NEW ANTIINFLAMMATORY STEROIDS Principal Investigator & Institution: Lee, Henry J.; Florida Agricultural and Mechanical Univ Tallahassee, FL 32307 Timing: Fiscal Year 2001; Project Start 05-JUN-2000; Project End 30-APR-2005 Summary: The use of corticosteroids in the treatment of inflammatory conditions has been limited primarily due to their systematic suppressive effects on the adrenal function and the immune system. To overcome this limitation, a focused effort has been made to synthesize locally active anti- inflammatory steroids without systemic adverse effects based on the antedrug concept. In this approach, antedrugs are designed to exert their actions at the application site, but to undergo the systemic circulation. Thus, the true antedrug acts locally and is devoid of systemic adverse effects. It is proposed to
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synthesize a new group of steroidal antedrugs and evaluate them comprehensively with respect to their local to systemic pharmacological activities. To further delineate the mode of action of the new steroids, their receptor binding characteristics, effects on pituitary adrenal function, glycogen deposition, liberation of prostanoids and nitric oxide (NO) will be studied. Results of these studies will yield valuable insight into the structural characteristics for the maximum separation of local anti-inflammatory activity from systemic adverse effects, and the mode of action of these non-systemic antiinflammatory steroids with the promise of providing a solid rational basis for development of new potent anti-inflammatory steroids devoid of systemic side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNTHESIS OF TARGET SPECIFIC ANTICANCER AGENTS Principal Investigator & Institution: Lee, Ken; Jackson State University 1400 John R. Lynch St Jackson, MS 39217 Timing: Fiscal Year 2001 Summary: Synthesis of series of steroidal conjugates of cisplatin is proposed as target specific anti-cancer agents. Estradiol, testosterone, and progesterone derivatives, which may lead the agents and deliver cisplatin to the tumor organ are chose for breast and testicular cancers having steroidal receptors. The conjugation between steroid and ciplatin is to use the carboxylate group binding the platinum metal well. Such carboxylate group will be introduced to 16-, 17- or 20-position of related steroids by nucleophilic addition reaction of related ester with ketone of steroids. The octanol/phosphate buffer partition coefficients of synthesized conjugated will be measured for the lipophilicity of new agents. The anti-tumor activity and other pharmacological activity of conjugates and steroidal derivatives will be tested at School of Pharmacy, Florida A&M University, Tallahassee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: T CELL/CYTOKINE MEDIATED EXPERIMENTAL ILEITIS Principal Investigator & Institution: Cominelli, Fabio; Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001 Summary: There is increasing evidence that CD4+ T cells and their cytokines may play a key role in the pathogenesis of Crohn's disease (CD), one of the known idiopathic inflammatory bowel disease (IBD's). One of the difficulties encountered in identifying the primary immunological and/or cytokine-induced abnormality(ies) in CD has been the lack of appropriate animal models. The unique feature of this proposal is that we will use a new strain of mice, referred to as SAMP1/Yit, that develop enteritis spontaneously without genetic or immunologic manipulation. These mice develop disease only when colonized with normal murine intestinal flora, and not when housed under free conditions. Therefore, the overall objective of Project 1 is to investigate the key pathogenic mechanisms, particularly those involving T cells and Thy cytokines, underlying this spontaneous murine model which closely resembles human CD. In order to achieve our goals we will: (1) Characterize the features of intestinal inflammation as well as the response to conventional immunosuppressive therapy in SAMP1/Yit mice. The penetrance of disease, the clinical phenotype of SAMP1/Yit mice at different ages as well as the response to steroids and immunosuppressive agents will be investigated. The similarities with human CD will be clearly defined in a systematic fashion. (2) Define the role of the immune response in the develop inflammation in
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SAMP1/Yit mice. Characterization of T cell phenotype and function in conjunction with a series of T-cell adoptive transfer as well as studies using bone marrow chimeras will be performed to precisely define the role of T-cells in this model. (3) To characterize the role of primary immunoregulatory cytokines in mediating chronic intestinal inflammation in SMP1/Yit mice. The key role of pro- inflammatory and immunological cytokines which have been implicated in the inductive phase of Th1 polarization including TNF, IL-12, and IL- 18 will be investigated by measuring their expression during the development of gut disease as well as by specific neutralization with monoclonal antibody therapy. In addition, the critical role if each cytokines will be assessed by studying the effects of specific genetic deletions of TNF, IL-12 and IL-18 on the development of intestinal inflammation in this model. The ultimate goal of Project 1 is to define the key pathogenic mechanisms in experimental CD mediated by CD4+ T cell and cytokines in order to develop disease-modifying treatment modalities for this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TESTOSTERONE EFFECTS ON DIAPHRAGM MUSCLE FATIGUE Principal Investigator & Institution: Blanco, Cesar E. Assistant Professor; Biokinesiology & Phys Therapy; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 30-NOV-2002 Summary: (Adapted from the applicant's abstract): Anabolic-androgenic steroids (AAS), such as testosterone, are used to increase mass and strength. Clinically, they are used to treat hypogonadism, age-related decrements in muscle function, AIDS-related muscle wasting and, muscle wasting associated with chronic obstructive pulmonary disease (COPD). Pharmacologic AAS treatment is effective in decreasing diaphragm (DIA) fatigue during direct muscle stimulation in female rats. Identical AAS treatment of male rats had no effect on DIA muscle fatigue using the same stimulation paradigm. Peripheral muscle fatigue can result from failure in neuromuscular transmission, excitation-contraction coupling, or contraction. The contribution of neurotransmission failure to muscle fatigue cannot be determined using direct muscle stimulation. Preliminary results suggest that chronic testosterone treatment of sedentary adult male rats decreases DIA fatigue during repetitive nerve stimulation, decreases the contribution of neuromuscular transmission to DIA fatigue, selectively improves neuromuscular transmission of type 2X and 2B DIA fibers and, also selectively increases axon terminal and motor endplate size at the neuromuscular junction of type 2X and 2B DIA fiber. We have previously shown that testosterone treatment increases the steadystate levels of choline acetyltransferase (ChAT) mRNA in motoneurons of the lateral motor columns of the cervical and lumbar spinal cord. These data suggest that testosterone may modulate the expression of proteins essential to synaptic transmission at the neuromuscular junction. The goal of this research proposal is to test the hypothesis that testosterone decreases peripheral muscle fatigue through the improvement of neuromuscular transmission in the rat DIA. Indeed, improved neuromuscular transmission may underlie the effects of AAS on muscle function. The four specific aims will be addressed in four experiments and provide data to test this hypothesis. Experiment I will determine the effects of pharmacologic testosterone treatment on neuromuscular transmission failure to peripheral DIA fatigue. Experiment II will determine the correlation between developmental testosterone fluctuations during postnatal development and DIA fatigue. Experiment III will examine the effect of pharmacologic testosterone treatment on synaptic transmission and neuromuscular
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junction morphology in the DIA muscle. Finally, the ability of testosterone to regulate ChAT and vesicular acetylcholine transporter mRNA levels in phrenic motoneurons and mRNA levels for the alpha-subunit of the nicotinic acetylcholine receptor subunit (alpha-AchR) in the DIA muscle will be determined in Experiment IV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF GENDER ON POST-TRAUMATIC INFLAMMATION Principal Investigator & Institution: Bramlett, Helen Marie. Neurological Surgery; University of Miami Box 016159 Miami, FL 33101 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2006 Summary: (provided by applicant): The efficacy of estrogen treatment in several injury models has been previously reported. Our own recent work has demonstrated a reduction in contusion volumes following traumatic brain injury (TBI) in female rats versus males or ovariectomized females. Although several mechanistic pathways for this neuroprotection have been explored, one that has not and is important after TBI is inflammation. TBI produces a robust inflammatory response that is both acute and chronic in duration. Several investigators using other models have reported the ability of estrogen to inhibit specific components of the inflammatory cascade. The proposed studies will assess differences between males and females after TBI with regard to posttraumatic inflammation. Four specific aims are proposed to address this issue. In specific aim 1, we will measure levels of proinflammatory cytokines and determine the cellular source of these initiators of inflammation. These studies will provide novel data on differences between males and females and in addition, by using ovariectomized females, the influence of reproductive steroids. In the second aim, we will study regional patterns of iNOS expression and determine if this response is sex and hormonedependent. Because iNOS has been implicated in the pathogenesis of TBI, this inflammatory response to trauma requires investigation in the present setting. Specific aim 3 will assess whether estrogen's effect on the inflammatory cascade after TBI is due to antioxidant properties or receptor-mediated mechanisms. Because estrogen has been reported to effect various components of the inflammatory cascade, its effect on traumainduced inflammatory processes requires further investigation. Results from this study will provide novel data for the potential use of neurohormones in the treatment of TBI. In the final aim, estrogen isomers or specific estrogen receptor antagonist/agonist will be administered after TBI to assess recovery of function. Taken together, these experiments will provide new data on the importance of neurohormones on structural and functional outcome after TBI. Established methods including rodent models of TBI, behavioral tests, as well as immunocytochemical and molecular approaches will be used in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT Principal Investigator & Institution: Freemark, Michael S. Pediatrics; Duke University Durham, NC 27706 Timing: Fiscal Year 2003; Project Start 01-MAY-1988; Project End 31-MAY-2008 Summary: (provided by applicant): Prolactin (PRL) and placental lactogen (PL) stimulate fat deposition, weight gain, and leptin production in rodents and humans, suggesting that lactogens play roles in maternofetal lipid metabolism and obesity. The mechanisms by which lactogens promote fat storage and weight gain are unknown. We hypothesize: (a) that lactogens promote fat deposition through induction of
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adipogenesis, the process of differentiation of adipocytes from stromal precursors; (b) that adipogenic effects of lactogens are mediated through induction of transcription factors including PPARkhi-2; (c) that PPARkhi-2 induction is mediated through activation of Stat5; and (d) that adipogenic effects of lactogens are modulated by insulin, IGF-1, glucocorticoids, and sex steroids. To test these hypotheses we will examine effects of exogenous PRL and PL on adipogenesis in 3T3-L1 preadipocytes, primary mouse preadipocytes and embryonic fibroblasts and the effects of constitutive expression of PL in a novel 3T3-L1 cell line. To determine if lactogenic signaling is required for preadipocyte differentiation, we will compare rates of adipogenesis in preadipocytes of PRL receptor (PRLR)-deficient mice with rates of adipogenesis in cells of wild-type littermates. To characterize effects of lactogens on PPARkhi expression we will examine effects of PRL and PL on PPARkhi1 and 2 mRNA and protein levels in 3T3-L1 cells, primary preadipoyctes, mouse embryonic fibroblasts and will compare PPARkhi expression in tissues of PRLR deficient mice with that in wild-type littermates, We will examine effects of lactogens on transcriptional activation of the human and mouse PPARkhi-2 promoters expressed in 3T3-L1 cells and will compare the time course of expression of PPARkhi1I and 2 mRNAs in PRL-treated cells with that of ADD1 and c/EBPs beta, delta, and alpha. To test the hypothesis that induction of PPARkhi-2 is mediated through activation of Stat5, we will determine if lactogens induce binding of STAT 5 to consensus binding sites in the human and mPPAR c-2 promoters. We will examine the effect of mutating PPARkhi-2 Stat5 consensus sequences on lactogendependent activation of PPAR gamma2 transcription, and the effect of a dominantnegative STAT5 construct on the induction of PPARkhi mRNA and protein levels in 3T3-L1 cells. Finally, to test the hypothesis that the adipogenic effects of the lactogens are modulated by sex steroids, we will examine the effects of progesterone and estradiol on the adipogenic effects of PRL in 3T3-L 1 cells and the effects of progesterone supplementation on fat deposition and leptin production in PRLR-deficient mice. The results of our studies should provide new insist into the roles of pituitary and placental hormones in adipose development and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF SEX HORMONES ON COGNITION Principal Investigator & Institution: Janowsky, Jeri S. Professor; Neurology; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 20-APR-1994; Project End 30-NOV-2005 Summary: (provided by applicant): The goal of this research program has been to use a cognitive neuroscience framework to delineate the cognitive processes and neural systems that are modulated by sex steroids in aging. We continue this approach in this renewal (Years 8-11) by examining the effects of aging and sex steroids on the modulation of emotional memory. The role of the amygdala in arousal, and its importance in the affective modulation of memory, have been well delineated at the pharmacological, physiological and behavioral levels in both animals and humans. Studies also show that the amygdala and hippocampus have sex steroid receptors, and that sex steroids modulate their anatomy, physiology and function. However, neither the effects of aging, nor the effects of sex steroids on the amygdala's modulation of memory have been examined. Thus, we propose to expand our studies to examine the effects of sex steroids on the modulation of emotion and emotional memory in aging. We will examine age-related changes in emotion and emotional memory by comparing arousal, ratings of valence, and emotional memory for words, faces, pictures, stories, and fear conditioning in healthy older and younger people (Aim 1/Study 1). We
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examine sex steroid effects on these same measures in older women by examining the effects on performance of estrogen, estrogen + progesterone, estrogen + testosterone replacement versus no replacement (Aim 2/Study 2). Finally, we will examine sex steroid effects on these measures in older men by examining the effects of testosterone administered in a double blind placebo controlled manner (Aim 3/Study 3). We hypothesize that the memory impairment in aging for emotional stimuli will not be due to a primary lack of arousal or inability to recognize emotion, but rather the transfer of that information for use by the memory encoding and storage system. We also hypothesize that sex steroids will modify emotional memory in the elderly. This work will expand our understanding of factors that modify cognition, and in particular memory in aging, as well as the potential neural basis of these changes. This work is particularly important because those over 65 years of age are the fastest growing segment of the population, and are also those most likely to have cognitive decline and age-related degenerative diseases that preclude productivity and independence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT EVALUATION IN PREMENSTRUAL SYNDROME PATIENTS Principal Investigator & Institution: Freeman, Ellen W. Research Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-FEB-1985; Project End 31-JAN-2002 Summary: Premenstrual syndrome (PMS) is a complex, chronic, menstrually-related disorder, which is reported at severe levels that impairs functioning by 5-10 percent of reproductive-age women. Severe PMS is associated with diminished productivity, lost work time in the prime years of life, and troubled interpersonal relationships, particularly with the partner and children. Only in recent years, and resulting from these studies and other research, has there been scientific information on the efficacy and safety of treatments and investigation of the etiology of PMS. The investigators conceptualize PMS as mood and behavioral changes that derive from central effects, possibly an altered central nervous system (CNS) sensitivity involving changes of gonadal-adrenal steroids. Building on findings of serotonergic involvement in PMS symptoms, the investigators propose to complete and extend studies of the efficacy and safety of serotonergic antidepressant treatment for PMS. The aims of this competing renewal application are to: 1) complete a large clinical study comparing the efficacy of a serotonergic and a noradrenergic antidepressant with a sample size sufficient for definitive results; 2) conduct a randomized, double-blind, placebo-controlled study of intermittent dosing with sertraline administered in the symptomatic premenstrual phase compared to daily dosing; and 3) examine the impact of PMS on functioning, productivity, health care utilization and quality of life before and after medical treatment in aim #1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIBUTYLTIN HORMONE METABOLISM
INDUCED
PERTURBATIONS
IN
STEROID
Principal Investigator & Institution: Mason, Andrew Z.; California State University Long Beach 1250 Bellflower Blvd Long Beach, CA 90840 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: There has been increasing concern over the role of dietary and environmental steroids, and steroid mines on the increased occurrence of various abnormalities in
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steroidally responsive target tissues in both males females. In mammals, these compounds often appear to elicit their effect at the transcriptional level through their competitive interaction for the estrogen/androgen receptors. However, the tight focus on mammalian models of endocrine disruption at the receptor level has resulted in a tendency to overlook at the importance of the effects of these compounds on other susceptible pathways critical for normal reproductive behavior. The environmental pollutant tributyltin (TBT) may represent a new class of endocrine disruptor that elicits its effects by directly perturbing the pathways governing steroidogenesis rather than acting indirectly via the estrogen receptor. The compound can act as a potent 'antiestrogen' causing sex reversal in certain species of mollusc at concentrations as low as o.5ng1-1. This condition, termed imposex, describes a state of pseudo- hermaphrodism where afflicted females exhibit spermatogenic activity and secondary male characteristics including a penis where a penal duct and a vas deferens. At this present time, the mechanisms by which TBT causes masculinization in these organisms is unknown and its potential for causing similar perturbations in sex differentiation and expression in other species, including mammals, remains to be established. The primary, long-term goal of the proposed study is to determine the sub-lethal model of toxicity of the compound and assess whether TBT and other toxicological analogues could constitute an environmental hazard to humans. Preliminary data indicate that TBT may cause imposex by three independent mechanisms that either directly, or indirectly, collectively increase the androgenic titer of steroids, thereby inducing maleness. In this proposal, a series of in vivo and in vitro experiments using the TBT-sensitive mollusk, Nucella emarginata, and human prostate cancer and hepatoma cell lines have been designed to specifically test each of the identified mechanisms of action and determine if TBT acts via perturbing aromatase activity, androgen conjugation and elimination or by potentiation gonadotrophin neuropeptide release. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TROPHOBLAST MDR EFFLUX SYSTEM AND FETAL PROTECTION Principal Investigator & Institution: Audus, Kenneth L.; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: Recent studies in animal models have indicated that the multi-drug resistant (MDR) gene product, P-glycoprotein (Pgp), of the placenta has a significant role in reducing chemical exposure to the fetus and the incidence of birth defects. Pgp is an active, polyspecific membrane- bound transporter expressed in tumor and normal tissues, including the placenta. In humans, Pgp is localized to the syncytio- and cytotrophoblasts and is expressed throughout pregnancy. However, Pgp's role in controlling the disposition of drugs and steroids between the fetal and maternal compartments is unknown. The objective of this proposal is to characterize the Pgp efflux mechanism of the trophoblast with respect to expression and transporting xenobiotics (e.g., anti-cancer agents, phenobarbital, rifampicin) and steroids of pregnancy (e.g., progesterone) and its regulation by these substances. Under Aim 1o of this proposal we will elucidate (a) the mRNA and protein expression, and (b) the localization of MDR1 in the human trophoblast. In Aim 2 we will determine (a) the functional significance and (b) the asymmetry of human trophoblast transport of selected xenobiotics and steroid hormones. Aim 3 studies are directed at characterization of the regulatory mechanism(s) by which certain xenobiotics and steroid hormones control (a) the expression and (b) the function of MDR1 of the human trophoblast. We expect that at the conclusion of this proposal we will have established the role of Pgp and related mechanisms (e.g. breast
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cancer resistance protein) of the trophoblast in transporting substrates that include xenobiotics and the steroid hormones. We also expect to establish a putative role and the biochemical mechanisms by which certain xenobiotics and steroid hormones modulate Pgp expression and/or function. Our long term goal is to develop a detailed understanding of the mechanisms controlling drugs and drugs of abuse distribution across the human detailed understanding of the mechanisms controlling drugs and drugs of abuse distribution across the human trophoblast and to identify appropriate in vitro techniques that can lead the way to the future design and development of drugs for pregnancy that reduce risk to the health of the fetus and the mother. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TYPE II 3BETA HSD GENE--REGULATION OF DHEAS SYNTHESIS Principal Investigator & Institution: Hornsby, Peter J. Professor; Physiology; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2003 Summary: In humans and a few other primates, the adrenal cortex in the adult individual secretes androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), as well as glucocorticoids and mineral-corticoids. The synthesis of these steroids is performed by a unique cell type of the cortex, the zona reticularis cell. Although the function of these steroids is unknown, the plasma level of DHEAS in the young adult human exceeds that of all other steroid hormones. Equally remarkable is an age-related decline in this level, resulting from the decreased synthesis by the adrenal cortex. This likely results from an age-related loss of ZR cells. They key enzymatic feature of the ZR cell that causes DHEA synthesis is its low expression of 3betahydroxysteroid dehydrogenase (3beta-HSD). The aims of this proposal are to investigate the molecular and cellular biology of the differentiation of the zones of the human adrenal cortex, specifically the zona reticularis (ZR) and the zona fasciculata (ZF), focusing on the following questions: To clone and characterize a protein that binds to a regulatory region of the type II 3beta-HSD gene and differs in abundance between ZR cells and ZF cells. The bovine adrenal cortex will be used as a source of the protein which will be purified by affinity chromatography; To investigate the possible regulation of ZR cell number by apoptosis. This will be performed using pure isolated ZR cells in culture; To study the behavior of pure ZR cells in a new model of adrenocortical cell and molecular biology using transplantation of adrenal cells into adrenalectomized scid mice. In this model, human ZF cells replace the function of the animals' own adrenal glands. The ability of ZR cells to form functional vascularized tissue in this model will be tested. The emphasis of the proposal is on adrenocortical cell differentiation, using the type II 3beta-HSD gene as the initial focus. More generally, the three specific aims link to explore the control of the differentiation of the ZR cell and its different pattern of gene expression. Its potentially greater susceptibility to apoptosis is one reflection of this pattern of gene expression. Cell transplantation offers the possibility of future testing of molecular mechanisms of zonation under controlled in vivo conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: UTERINE ENDOMETRIOSIS
BIOLOGY
AND
THE
PATHOPHYSIOLOGY
OF
Principal Investigator & Institution: Osteen, Kevin G. Professor; Obstetrics and Gynecology; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917
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Timing: Fiscal Year 2001; Project Start 15-APR-1999; Project End 31-MAR-2004 Summary: This application requests funds to establish a Specialized Cooperative Center in Reproduction Research focused on the theme "Uterine Biology and the Pathophysiology of Endometriosis". Endometriosis is a common gynecologic disorder associated with dysmenorrhea, pelvic pain and reduced fertility affecting 10-15% of all women and up to 50% of women with infertility. We will apply state-of-the-art cellular and molecular biology techniques using human tissues and animal models to examine key cellular mechanisms by which endometriosis is initiated and progresses. Most cases of endometriosis can be attributed to ectopic implantation of fragments of endometrium entering the peritoneal cavity following reflex menstruation. Our central hypothesis is that steroids, acting through local cytokines and growth factors, co-regulate essential endometrial proteins which mediate the adhesion, invasive implantation and the inflammatory response that accompanies the ectopic growth of endometrium. Immune cytokines can disrupt the normal regulation of these proteins, contribute further to the disease process. We have designed three, interactive research projects to address the central elements of our hypothesis. Project I examines the control of matrix metalloproteinases, enzymes essential for mediating the invasive establishment of ectopic I examines the control of matrix metalloproteinases, enzymes essential for mediating the invasive establishment of ectopic sites of human endometrium within the peritoneal cavity. This project also examines the consequences of cytokine-mediated disruption of the expression of these enzymes using human tissue in a nude mouse model. Project II examines the regulations of RANTES, a potent inflammatory chemokine capable of activating immune cells and disrupting gene regulation at implant sites of endometriosis. This project will also utilize human tissues and the nude mouse model to examine RANTES expression in vivo. Project III examines a unique family of proteins, metalloproteinase/disintegrins, which may be important for the initial epithelial cell-cell adhesion required for invasion of endometrial fragments into the peritoneal wall. These molecules have been linked to ovo-implantation processes and appear to be regulated by both steroids and inflammatory cytokines. The Center will include administrative, morphology and molecular biology cores to support all research project. Directors of each project and core reside at Vanderbilt University except for the director of Project II who resides at the University of California, San Francisco. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UTERINE VASCULAR RESPONSE TO STEROID SIGNALING Principal Investigator & Institution: Bernstein, Ira M. Associate Professor; Obstetrics and Gynecology; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2001; Project Start 06-JUL-1999; Project End 30-JUN-2003 Summary: The maternal vascular transformation required for successful pregnancy is initiated during the menstrual cycle by a coordinated series of hemodynamic adaptations that appear to be endocrinologically mediated. These events include a decrease in uterine artery vascular impedance and an increase in uterine blood flow that set the stage for implantation and trophoblast development. The failure of this uterine vascular response is associated with specific reproductive inadequacy, including infertility, fetal growth restriction and pre-eclampsia. While estrogen and progesterone have been clearly implicated as signals mediating the adaptive hemodynamic responses, the extent to which these steroids are both necessary and sufficient as primary signals in the human is unknown. Additionally, the mechanisms by which estrogen and
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progesterone influence the uterine vasculature are unknown. This project is focused on defining, in humans, changes in the uterine and systemic circulation that occur through the menstrual cycle. Specific hormonal effects within the menstrual cycle will be examined as a function of add-back estrogen and progesterone in women with drug induced ovarian suppression. These responses will be individually compared to spontaneous ovulatory cycles. We intend to demonstrate: 1) that the uterine vascular response is unique and distinguishable from the systemic response through the menstrual cycle, 2) that these (both uterine and systemic) responses result specifically from the action of estrogen and progesterone. 3) that estrogen and progesterone influence uterine artery hemodynamics by their effect on endometrial vascular growth via co-regulation of VEGF and VEGF receptors, including neuropilin, the most recently described VEGF receptor. 4) that endogenous steroid responses can be reproduced using an ovarian suppression model with hormonal add-back validating a powerful research technique. To show this we will measure, using Doppler ultrasound, the changes in uterine artery impedance and blood flow as well as the changes in systemic vascular resistance and cardiac output that attend the menstrual cycle, while simultaneously examining the endometrium via biopsy. We will assess, through this unique human model, the isolated and inter-related effects of the specific signal (estrogen and progesterone), with the effector (VEGF), and the responses (angiogenesis, vascular remodeling). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFLUENCES
VASCULAR
REACTIVITY--GENDER
AND
HORMONAL
Principal Investigator & Institution: Duckles, Sue P. Professor; Pharmacology; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 01-JUL-1994; Project End 30-JUN-2002 Summary: (Adapted from the application) Actions of estrogen on function of endothelial NOS may account for cerebrovascular protection. Thus, the first hypothesis is: 1) cerebrovascular responses involving NOS are affected by estrogen. Rat middle cerebral arteries in vitro will be used to test the influence of sex and gonadal steroids, comparing males and cycling females, control or gonadectomized and steroid-replaced. The investigator will compare myogenic tone in arteries from males and females and test whether NOS inhibition abolishes gender or estrous cycle differences. Possible K+ channel involvement will be investigated. Since shear stress stimulates the activity of NOS, the PI will test whether flow induced vasodilation is influenced by estrogen status and investigate modulation by gender and gonadal steroids. As a control, effects of gender and gonadal steroids on vasodilator responses to increased extracellular K+, which does not involve NOS will be investigated. The second hypothesis is: 2) estrogen acts by regulating levels of eNOS protein. Responses to endothelial dependent vasodilators, levels of NOS protein by Western blot and NOS activity will be measured, and NOSIII-deficient mice will be studied. For the third specific aim, the PI will test whether: 3) estrogen modulates effects of melatonin by a selective action on MT2 receptor mediated vasodilation. Circadian variation in cardiovascular disease onset has been shown and estrogen regulates vascular sensitivity to melatonin. The PI will determine whether melatonin causes constriction of cerebral arteries through MT1 and dilation via MT2 receptors. Influence of sex, transmural pressure, artery size and endothelial factors will be investigated. The PI will also test whether dilator responses via MT2 receptors are preferentially enhanced by estrogen exposure and using RT-PCR whether gonadal hormones alter expression of melatonin receptor subtypes. The final
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hypothesis is: 4) effects of estrogen are mediated by the classical estrogen receptor Estrogen receptor antagonists and estrogen receptor knockout mice will be used to test whether this receptor accounts for effects on cerebrovascular reactivity. Given the enormous impact of hormone replacement therapy, knowledge of the effects of gonadal steroids and melatonin on the cerebral circulation is essential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VESICULAR REGULATION
GLUTAMATE
TRANSPORT:
NEUROSTEROID
Principal Investigator & Institution: Bridges, Richard J. Professor; Pharmaceutical Sciences; University of Montana University Hall 202 Missoula, MT 598124104 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2003 Summary: (provided by applicant): As the primary excitatory transmitter in the mammalian CNS, L-glutamate participates in fast excitatory signaling, as well as the higher order processing required in development, plasticity, learning and memory. The pervasiveness of this system in the normal functioning of the CNS is equally matched by its association with a wide variety of neurological disorders, including acute stroke, chronic neurodegenerative diseases, epilepsy, depression, Parkinson's disease, and schizophrenia. Whether for the purposes of elucidating normal signaling mechanisms, pathological processes, or novel therapeutic strategies, investigations aimed at modulating this system have most often focused at the level of glutamate receptors. Recent work has identified a potentially novel mechanism through which glutamatemediated excitatory transmission may be regulated at the level of glutamate release. While delineating the pharmacological specificity of the transporter responsible for loading L-glutamate into synaptic vesicles, it was found that this system appears to be potently inhibited by select steroids. This suggests that these compounds might play a role in determining the amount of L-glutamate present in synaptic vesicles and, consequently, the quantity actually released during excitatory transmission. If such a mechanism exists, it represents a non-genomic pathway through which steroids may regulate one of the most prominent transmitter systems in the CNS. Importantly, it also identifies a novel therapeutic site that could be exploited to correct imbalances in the glutamate systems that may underlie several debilitating neurological disorders. As much as identifying a new regulatory mechanism for excitatory transmission would represent a substantial breakthrough, the potential importance of this mechanism must be tempered by what is not known. Thus, the goal of the proposed experiments is to address fundamental issues related to specificity and potency of action, which must first be explored before the full relevance of this novel modulatory mechanism can be either appreciated or systematically investigated on a larger scale. It is for these reasons that we believe the R21 program represents the most appropriate grant mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National
3 Adapted
from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
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Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “steroids” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for steroids in the PubMed Central database: •
[gamma]-Aminobutyric acid, acting through [gamma]-aminobutyric acid type A receptors, inhibits the biosynthesis of neurosteroids in the frog hypothalamus. by DoRego JL, Mensah-Nyagan GA, Beaujean D, Vaudry D, Sieghart W, Luu-The V, Pelletier G, Vaudry H. 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17677
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A brassinosteroid-insensitive mutant in Arabidopsis thaliana exhibits multiple defects in growth and development. by Clouse SD, Langford M, McMorris TC. 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157882
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A Corticosteroid-Induced Gene Expressing an "IsK-Like" L+ Channel Activity in Xenopus Oocytes. by Attali B, Latter H, Rachamim N, Garty H. 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41648
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A Mechanism for the Antiinflammatory Effects of Corticosteroids: The Glucocorticoid Receptor Regulates Leukocyte Adhesion to Endothelial Cells and Expression of Endothelial-Leukocyte Adhesion Molecule 1 and Intercellular Adhesion Molecule 1. by Cronstein BN, Kimmel SC, Levin RI, Martiniuk F, Weissmann G. 1992 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50263
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A new hypothesis for how sex steroid hormones regulate bone mass. by Lorenzo J. 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156115
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Accumulation of 3-Ketosteroids Induced by Itraconazole in Azole-Resistant Clinical Candida albicans Isolates. by Marichal P, Gorrens J, Laurijssens L, Vermuyten K, Van Hove C, Le Jeune L, Verhasselt P, Sanglard D, Borgers M, Ramaekers FC, Odds F, Vanden Bossche H. 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89540
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Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. by Lala DS, Syka PM, Lazarchik SB, Mangelsdorf DJ, Parker KL, Heyman RA. 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24602
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An Early C-22 Oxidation Branch in the Brassinosteroid Biosynthetic Pathway. by Fujioka S, Takatsuto S, Yoshida S. 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166619
4 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Arabidopsis det2 Is Defective in the Conversion of (24R)-24-Methylcholest-4-En-3One to (24R)-24-Methyl-5[alpha]-Cholestan-3-One in Brassinosteroid Biosynthesis. by Noguchi T, Fujioka S, Takatsuto S, Sakurai A, Yoshida S, Li J, Chory J. 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59322
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Attenuated sensitivity to neuroactive steroids in [gamma]-aminobutyrate type A receptor delta subunit knockout mice. by Mihalek RM, Banerjee PK, Korpi ER, Quinlan JJ, Firestone LL, Mi ZP, Lagenaur C, Tretter V, Sieghart W, Anagnostaras SG, Sage JR, Fanselow MS, Guidotti A, Spigelman I, Li Z, DeLorey TM, Olsen RW, Homanics GE. 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23157
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BAS1: A gene regulating brassinosteroid levels and light responsiveness in Arabidopsis. by Neff MM, Nguyen SM, Malancharuvil EJ, Fujioka S, Noguchi T, Seto H, Tsubuki M, Honda T, Takatsuto S, Yoshida S, Chory J. 1999 Dec 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24817
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BIN2, a New Brassinosteroid-Insensitive Locus in Arabidopsis. by Li J, Nam KH, Vafeados D, Chory J. 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117958
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Brassinosteroid Mutants Uncover Fine Tuning of Phytochrome Signaling. by Luccioni LG, Oliverio KA, Yanovsky MJ, Boccalandro HE, Casal JJ. 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148967
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Brassinosteroid-Regulated Gene Expression. by Mussig C, Fischer S, Altmann T. 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166518
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Characterization of Brassinazole, a Triazole-Type Brassinosteroid Biosynthesis Inhibitor. by Asami T, Min YK, Nagata N, Yamagishi K, Takatsuto S, Fujioka S, Murofushi N, Yamaguchi I, Yoshida S. 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58985
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Characterization of the Steroid-Metabolizing Capacity of the Hepatic Cytochrome P450IIC5 Expressed in COS-1 Cells: 3[beta]-Hydroxysteroid Dehydrogenase/[Delta]5[right arrow]4 Isomerase Type Activity. by Trant JM, Lorence MC, Johnson EF, Shackleton CH, Mason JI, Estabrook RW. 1990 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=55252
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Cholesterol binding at the cholesterol recognition / interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide. by Li H, Yao ZX, Degenhardt B, Teper G, Papadopoulos V. 2001 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14743
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Control of Specific Gene Expression by Gibberellin and Brassinosteroid. by Bouquin T, Meier C, Foster R, Nielsen ME, Mundy J. 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125081
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Covalent Modification of Proteins by Ligands of Steroid Hormone Receptors. by Takahashi N, Breitman TR. 1992 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50431
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CREB Binding Protein Acts Synergistically with Steroid Receptor Coactivator-1 to Enhance Steroid Receptor-Dependent Transcription. by Smith CL, Onate SA, Tsai M, O'Malley BW. 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38563
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Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D3. by Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, Ray R, Gliemann J, Willnow TE, Christensen EI. 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61138
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Cyclosporin A Potentiates the Dexamethasone-Induced Mouse Mammary Tumor Virus-Chloramphenicol Acetyltransferase Activity in LMCAT Cells: A Possible Role for Different Heat Shock Protein-Binding Immunophilins in Glucocorticosteroid Receptor-Mediated Gene Expression. by Renoir J, Mercier-Bodard C, Hoffmann K, Bihan SL, Ning Y, Sanchez ER, Handschumacher RE, Baulieu E. 1995 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41830
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Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7[alpha]-hydroxy dehydroepiandrosterone and 7[alpha]-hydroxy pregnenolone. by Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Bjorkhem I, Seckl J, Lathe R. 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24607
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Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase C[epsilon]. by Hodge CW, Raber J, McMahon T, Walter H, Sanchez-Perez AM, Olive MF, Mehmert K, Morrow AL, Messing RO. 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151152
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Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. by Baulieu EE, Robel P. 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34265
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Diazepam-Binding Inhibitor (DBI)-Processing Products, Acting at the Mitochondrial DBI Receptor, Mediate Adrenocorticotropic Hormone-Induced Steroidogenesis in Rat Adrenal Gland. by Cavallaro S, Korneyev A, Guidotti A, Costa E. 1992 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50388
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Differential In Vivo Regulation of Steroid Hormone Receptor Activation by Cdc37p. by Fliss AE, Fang Y, Boschelli F, Caplan AJ. 1997 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25723
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Ecdysteroid-Dependent Regulation of Genes in Mammalian Cells by a Drosophila Ecdysone Receptor and Chimeric Transactivators. by Christopherson KS, Mark MR, Bajaj V, Godowski PJ. 1992 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49491
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Ergosteroids: Induction of Thermogenic Enzymes in Liver of Rats Treated with Steroids Derived from Dehydroepiandrosterone. by Lardy H, Partridge B, Kneer N, Wei Y. 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41569
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Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation. by Lutz LB, Cole LM, Gupta MK, Kwist KW, Auchus RJ, Hammes SR. 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61109
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Expression of Biologically Active Human Corticosteroid Binding Globulin by Insect Cells: Acquisition of Function Requires Glycosylation and Transport. by GhoseDastidar J, Ross JB, Green R. 1991 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52094
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Expression of the Human Apolipoprotein E Gene Suppresses Steroidogenesis in Mouse Y1 Adrenal Cells. by Reyland ME, Gwynne JT, Forgez P, Prack MM, Williams DL. 1991 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51234
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Feed-Forward Control of Prostate Growth: Dihydrotestosterone Induces Expression of Its Own Biosynthetic Enzyme, Steroid 5[alpha]-Reductase. by George FW, Russell DW, Wilson JD. 1991 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52442
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Fluoxetine-Elicited Changes in Brain Neurosteroid Content Measured by Negative Ion Mass Fragmentography. by Uzunov DP, Cooper TB, Costa E, Guidotti A. 1996 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38038
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Functional Compensation by Egr4 in Egr1-Dependent Luteinizing Hormone Regulation and Leydig Cell Steroidogenesis. by Tourtellotte WG, Nagarajan R, Bartke A, Milbrandt J. 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85975
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High dose inhaled corticosteroids and dose dependent loss of diabetic control. by Faul JL, Tormey W, Tormey V, Burke C. 1998 Nov 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58840
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Identification and Selective Inhibition of an Isozyme of Steroid 5[alpha]- Reductase in Human Scalp. by Harris G, Azzolina B, Baginsky W, Cimis G, Rasmusson GH, Tolman RL, Raetz CR, Ellsworth K. 1992 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50427
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Identification of a Negative Regulatory Function for Steroid Receptors. by McDonnell DP, Vegeto E, O'Malley BW. 1992 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50381
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In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure. by Takahashi M, Wehrli FW, Hilaire L, Zemel BS, Hwang SN. 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123689
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Inhibition of Hormone-Stimulated Steroidogenesis in Cultured Leydig Tumor Cells by a Cholesterol-Linked Phosphorothioate Oligodeoxynucleotide Antisense to
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Diazepam-Binding Inhibitor. by Boujrad N, Hudson JR Jr, Papadopoulos V. 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46795 •
Interaction of three-way DNA junctions with steroids. by Kato T, Yano K, Ikebukuro K, Karube I. 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103303
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Involvement of Brassinosteroids in the Gravitropic Response of Primary Root of Maize. by Kim SK, Chang SC, Lee EJ, Chung WS, Kim YS, Hwang S, Lee JS. 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59062
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LEM1, an ATP-Binding-Cassette Transporter, Selectively Modulates the Biological Potency of Steroid Hormones. by Kralli A, Bohen SP, Yamamoto KR. 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42012
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Localization of 17[beta]-Hydroxysteroid Dehydrogenase and Characterization of Testosterone in the Brain of the Male Frog. by Mensah-Nyagan AG, Feuilloley M, DoRego JL, Marcual A, Lange C, Tonon MC, Pelletier G, Vaudry H. 1996 Feb 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39954
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Long-term suppression of Leydig cell steroidogenesis prevents Leydig cell aging. by Chen H, Zirkin BR. 1999 Dec 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24741
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Loss of Function of a Rice brassinosteroid insensitive1 Homolog Prevents Internode Elongation and Bending of the Lamina Joint. by Yamamuro C, Ihara Y, Wu X, Noguchi T, Fujioka S, Takatsuto S, Ashikari M, Kitano H, Matsuoka M. 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149072
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LY191704: A Selective, Nonsteroidal Inhibitor of Human Steroid 5[alpha]- Reductase Type 1. by Hirsch KS, Jones CD, Audia JE, Andersson S, McQuaid L, Stamm NB, Neubauer BL, Pennington P, Toomey RE, Russell DW. 1993 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46699
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Memory-Enhancing Effects in Male Mice of Pregnenolone and Steroids Metabolically Derived from it. by Flood JF, Morley JE, Roberts E. 1992 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48493
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Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). by Shrewsbury S, Pyke S, Britton M. 2000 May 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27379
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Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. by Gotzsche PC, Johansen HK. 1998 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28482
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Modulation of cognition-specific cortical activity by gonadal steroids: A positronemission tomography study in women. by Berman KF, Schmidt PJ, Rubinow DR, Danaceau MA, Van Horn JD, Esposito G, Ostrem JL, Weinberger DR. 1997 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23156
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Molecular cloning and characterization of a brassinosteroid-regulated gene from elongating soybean (Glycine max L.) epicotyls. by Zurek DM, Clouse SD. 1994 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=159174
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Molecular Determinants of Differential Ligand Sensitivities of Insect Ecdysteroid Receptors. by Wang SF, Ayer S, Segraves WA, Williams DR, Raikhel AS. 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85723
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N-cadherin is regulated by gonadal steroids in the adult hippocampus. by Monks DA, Getsios S, MacCalman CD, Watson NV. 2001 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14751
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Neuroprotective activity of a new class of steroidal inhibitors of the N-methyl-daspartate receptor. by Weaver CE Jr, Marek P, Park-Chung M, Tam SW, Farb DH. 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23383
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Neurosteroids, via [sigma] Receptors, Modulate the [3H]norepinephrine Release Evoked by N-Methyl-D-Aspartate in the Rat Hippocampus. by Monnet FP, Mahe V, Robel P, Baulieu E. 1995 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42044
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Neurosteroids: Pregnenolone in Human Sciatic Nerves. by Morfin R, Young J, Corpechot C, Egestad B, Sjovall J, Baulieu E. 1992 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49589
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Physiological-dose steroid therapy in sepsis [ISRCTN36253388]. by Yildiz O, Doganay M, Aygen B, Guven M, Kelestimur F, Tutus A. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125315
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Precursors of the Neurosteroids. by Prasad VV, Vegesna SR, Welch M, Lieberman S. 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43547
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Pregnancy-Related Steroids are Potential Negative Regulators of B Lymphopoiesis. by Medina KL, Kincade PW. 1994 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43999
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Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema. by Thomas KS, Armstrong S, Avery A, Po AL, O'Neill C, Young S, Williams HC. 2002 Mar 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100318
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Regulation of Transcript Levels of the Arabidopsis Cytochrome P450 Genes Involved in Brassinosteroid Biosynthesis. by Bancos S, Nomura T, Sato T, Molnar G, Bishop GJ, Koncz C, Yokota T, Nagy F, Szekeres M. 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166582
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Scavenger receptor class B, type I (SR-BI) is the major route for the delivery of high density lipoprotein cholesterol to the steroidogenic pathway in cultured mouse
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adrenocortical cells. by Temel RE, Trigatti B, DeMattos RB, Azhar S, Krieger M, Williams DL. 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28352 •
Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. by Griffin LD, Mellon SH. 1999 Nov 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23979
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Sex Differences in Seoul Virus Infection Are Not Related to Adult Sex Steroid Concentrations in Norway Rats. by Klein SL, Bird BH, Glass GE. 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112358
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Stepping down inhaled corticosteroids in asthma: randomised controlled trial. by Hawkins G, McMahon AD, Twaddle S, Wood SF, Ford I, Thomson NC. 2003 May 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156013
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Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess. by New MI, Wilson RC. 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23101
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Steroidogenic Potential of Lyophilized Mitochondria from Bovine Adrenocortical Tissue. by Prasad VV, Mathur C, Welch M, Lieberman S. 1992 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49036
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Steroids and Their Conjugates in the Mammalian Brain. by Mathur C, Prasad VV, Raju VS, Welch M, Lieberman S. 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45604
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Steroids Induce Acetylcholine Receptors on Cultured Human Muscle: Implications for Myasthenia Gravis. by Kaplan I, Blakely BT, Pavlath GK, Travis M, Blau HM. 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54900
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Stress-Induced Elevations of [gamma]-Aminobutyric Acid Type A Receptor- Active Steroids in the Rat Brain. by Purdy RH, Morrow AL, Moore PH Jr, Paul SM. 1991 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51699
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Structure of the ternary complex of human 17[beta]-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP +. by Sawicki MW, Erman M, Puranen T, Vihko P, Ghosh D. 1999 Feb 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15312
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Suppression of [Delta]5-androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells. by Chang HC, Miyamoto H, Marwah P, Lardy H, Yeh S, Huang KE, Chang C. 1999 Sep 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18006
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Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma. by Brocklebank D, Wright J, Cates C. 2001 Oct 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58536
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Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. by Caron KM, Soo SC, Wetsel WC, Stocco DM, Clark BJ, Parker KL. 1997 Oct 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23530
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The active form of the steroidogenic acute regulatory protein, StAR, appears to be a molten globule. by Bose HS, Whittal RM, Baldwin MA, Miller WL. 1999 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22068
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The Arabidopsis deetiolated2 mutant is blocked early in brassinosteroid biosynthesis. by Fujioka S, Li J, Choi YH, Seto H, Takatsuto S, Noguchi T, Watanabe T, Kuriyama H, Yokota T, Chory J, Sakurai A. 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157049
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The Arabidopsis DIMINUTO/DWARF1 gene encodes a protein involved in steroid synthesis. by Klahre U, Noguchi T, Fujioka S, Takatsuto S, Yokota T, Nomura T, Yoshida S, Chua NH. 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=143945
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The Arabidopsis dwarf1 Mutant Is Defective in the Conversion of 24Methylenecholesterol to Campesterol in Brassinosteroid Biosynthesis. by Choe S, Dilkes BP, Gregory BD, Ross AS, Yuan H, Noguchi T, Fujioka S, Takatsuto S, Tanaka A, Yoshida S, Tax FE, Feldmann KA. 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32104
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The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms? by Akwa Y, Ladurelle N, Covey DF, Baulieu EE. 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61162
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Transcriptional and Posttranscriptional Regulation of Arabidopsis TCH4 Expression by Diverse Stimuli. Roles of cis Regions and Brassinosteroids. by Iliev EA, Xu W, Polisensky DH, Oh MH, Torisky RS, Clouse SD, Braam J. 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166605
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with steroids, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “steroids” (or synonyms)
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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into the search box, and click “Go.” The following is the type of output you can expect from PubMed for steroids (hyperlinks lead to article summaries): •
A case for steroids in acute lung injury associated with the retinoic acid syndrome. Author(s): Cupitt JM. Source: Anaesthesia and Intensive Care. 2000 April; 28(2): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10788976&dopt=Abstract
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A case of erythromelalgia successfully controlled by systemic steroids and pentazocine--is it related to a unique subtype of neutrophilic dermatosis? Author(s): Suh DH, Kim SD, Ahn JS, Han KH, Cho KH, Eun HC, Youn JI. Source: The Journal of Dermatology. 2000 March; 27(3): 204-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774148&dopt=Abstract
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A case of multiple sclerosis with cerebral venous thrombosis: the role of lumbar puncture and high-dose steroids. Author(s): Gunal DI, Afsar N, Tuncer N, Aktan S. Source: European Neurology. 2002; 47(1): 57-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803195&dopt=Abstract
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A case of possible autoimmune bilateral vestibulopathy treated with steroids. Author(s): Schuler O, Strupp M, Arbusow V, Brandt T. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 June; 74(6): 825. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754370&dopt=Abstract
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A comparison of intrauterine insemination in superovulated cycles to intercourse in couples where the male is receiving steroids for the treatment of autoimmune infertility. Author(s): Robinson JN, Forman RG, Nicholson SC, Maciocia LR, Barlow DH. Source: Fertility and Sterility. 1995 June; 63(6): 1260-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750598&dopt=Abstract
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A genome-wide linkage scan for steroids and SHBG levels in black and white families: the HERITAGE Family Study. Author(s): Ukkola O, Rankinen T, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3708-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161500&dopt=Abstract
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A multicenter, open-label, comparative trial of two daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients: interim analysis. Author(s): Stratta RJ, Alloway RR, Hodge E, Lo A; Pancreas Investigators Vital Outcomes Trial (PIVOT) Study Group. Source: Clinical Transplantation. 2002 February; 16(1): 60-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982617&dopt=Abstract
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A novel technique for delivery of epidural steroids and diagnosing the level of nerve root pathology. Author(s): Larkin TM, Carragee E, Cohen S. Source: Journal of Spinal Disorders & Techniques. 2003 April; 16(2): 186-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679674&dopt=Abstract
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A pilot trial of tacrolimus, sirolimus, and steroids in renal transplant recipients. Author(s): Shapiro R, Scantlebury VP, Jordan ML, Vivas CA, Jain A, Hakala TR, McCauley J, Johnston J, Randhawa P, Fedorek S, Gray E, Chesky A, Dvorchik I, Donaldson J, Fung JJ, Starzl TE. Source: Transplantation Proceedings. 2002 August; 34(5): 1651-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176521&dopt=Abstract
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A randomised clinical trial of oral steroids in the treatment of carpal tunnel syndrome: a long term follow up. Author(s): Chang MH, Ger LP, Hsieh PF, Huang SY. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 December; 73(6): 7104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438475&dopt=Abstract
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A randomized clinical trial of oral versus intramuscular delivery of steroids in acute exudative pharyngitis. Author(s): Marvez-Valls EG, Stuckey A, Ernst AA. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2002 January; 9(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772663&dopt=Abstract
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A randomized trial of inhaled versus intravenous steroids in ventilator-dependent preterm infants. Author(s): Suchomski SJ, Cummings JJ. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 April-May; 22(3): 196-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948381&dopt=Abstract
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A review of the chemistry, biological action, and clinical applications of anabolicandrogenic steroids. Author(s): Shahidi NT. Source: Clinical Therapeutics. 2001 September; 23(9): 1355-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589254&dopt=Abstract
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ABCG2 transports sulfated conjugates of steroids and xenobiotics. Author(s): Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y. Source: The Journal of Biological Chemistry. 2003 June 20; 278(25): 22644-9. Epub 2003 April 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682043&dopt=Abstract
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Abnormalities of sodium pump function in hypertension and the role of endogenous cardiotonic steroids. Author(s): Doris PA. Source: Cell Mol Biol (Noisy-Le-Grand). 2001 March; 47(2): 391-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357900&dopt=Abstract
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Access of reproductive steroids to target tissues. Author(s): Hammond GL. Source: Obstetrics and Gynecology Clinics of North America. 2002 September; 29(3): 411-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353665&dopt=Abstract
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Actions of progesterone on human sperm: a model of non-genomic effects of steroids. Author(s): Baldi E, Krausz C, Luconi M, Bonaccorsi L, Maggi M, Forti G. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1995 June; 53(1-6): 199-203. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7626454&dopt=Abstract
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Acute candidiasis of the oro- and hypopharynx as the result of topical intranasal steroids administration. Author(s): Kyrmizakis DE, Papadakis CE, Lohuis PJ, Manolarakis G, Karakostas E, Amanakis Z. Source: Rhinology. 2000 June; 38(2): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10953848&dopt=Abstract
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Acute myopathy after status asthmaticus: steroids, myorelaxants or carbon dioxide? Author(s): Goh AY, Chan PW. Source: Respirology (Carlton, Vic.). 1999 March; 4(1): 97-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10339738&dopt=Abstract
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Acute rheumatic fever: whither steroids? Author(s): Nalk N, Bahl VK. Source: Indian Heart J. 2002 July-August; 54(4): 363-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462662&dopt=Abstract
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Acute tumor lysis syndrome in large B-cell non-Hodgkin lymphoma induced by steroids and anti-CD 20. Author(s): Abou Mourad Y, Taher A, Shamseddine A. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(3): 222-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764356&dopt=Abstract
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Acyclovir prophylaxis of varicella in children with renal disease receiving steroids. Author(s): Goldstein SL, Somers MJ, Lande MB, Brewer ED, Jabs KL. Source: Pediatric Nephrology (Berlin, Germany). 2000 April; 14(4): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10775074&dopt=Abstract
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Adolescent use of anabolic-androgenic steroids and relations to self-reports of social, personality and health aspects. Author(s): Kindlundh AM, Hagekull B, Isacson DG, Nyberg F. Source: European Journal of Public Health. 2001 September; 11(3): 322-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11582614&dopt=Abstract
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Adrenal and gonadal steroids inhibit IL-6 secretion by human marrow cells. Author(s): Gordon CM, LeBoff MS, Glowacki J. Source: Cytokine. 2001 December 7; 16(5): 178-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814313&dopt=Abstract
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Adrenal crisis due to inhaled steroids is underestimated. Author(s): Todd GR. Source: Archives of Disease in Childhood. 2003 June; 88(6): 554-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765935&dopt=Abstract
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Adrenal steroids in human prostatic cancer cell lines. Author(s): Koh E, Kanaya J, Namiki M. Source: Archives of Andrology. 2001 March-April; 46(2): 117-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297065&dopt=Abstract
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Adrenal steroids synthesis during acute infectious diseases in infants. Author(s): Longui CA, Zlochevsky ER, Bachega TA, Monte O. Source: J Pediatr Endocrinol Metab. 2002 November-December; 15(9): 1515-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503859&dopt=Abstract
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Adverse behavioral effects of treatment for acute exacerbation of asthma in children: a comparison of two doses of oral steroids. Author(s): Kayani S, Shannon DC. Source: Chest. 2002 August; 122(2): 624-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171842&dopt=Abstract
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Affinity of Helicobacter pylori to cholesterol and other steroids. Author(s): Trampenau C, Muller KD. Source: Microbes and Infection / Institut Pasteur. 2003 January; 5(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593968&dopt=Abstract
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Age and gender specific stimulation of creatine kinase specific activity by gonadal steroids in human bone-derived cells in culture. Author(s): Katzburg S, Ornoy A, Hendel D, Lieberherr M, Kaye AM, Somjen D. Source: J Endocrinol Invest. 2001 March; 24(3): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314745&dopt=Abstract
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Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression. Author(s): Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet LP, Hamid Q. Source: The Journal of Allergy and Clinical Immunology. 2003 June; 111(6): 1293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789232&dopt=Abstract
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Alcohol intake, androgen and glucocorticoid steroids in premenopausal women using oral contraceptives: an interventional study. Author(s): Sarkola T, Adlercreutz H, Heinonen S, Eriksson CJ. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 August; 78(2): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566440&dopt=Abstract
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Alterations in sex steroids and gonadotropins in post-menopausal women subsequent to long-term mifepristone administration. Author(s): Heikinheimo O, Ranta S, Grunberg S, Spitz IM. Source: Steroids. 2000 October-November; 65(10-11): 831-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108895&dopt=Abstract
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Altered gonadal steroidogenesis in critical illness: is treatment with anabolic steroids indicated? Author(s): Spratt DI. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2001 December; 15(4): 479-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800519&dopt=Abstract
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Altered reflex control of cutaneous circulation by female sex steroids is independent of prostaglandins. Author(s): Charkoudian N, Johnson JM. Source: The American Journal of Physiology. 1999 May; 276(5 Pt 2): H1634-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10330248&dopt=Abstract
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An additional dimension to the efficacy of epidural steroids. Author(s): Cousins MJ. Source: Anesthesiology. 2000 August; 93(2): 565; Author Reply 566-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910508&dopt=Abstract
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An induction versus no-induction protocol in anticalcineurin-based immunosuppression using very low-dose steroids. Author(s): Charpentier B. Source: Transplantation Proceedings. 2001 June; 33(4 Suppl): 3S-10S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406262&dopt=Abstract
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Anabolic androgenic steroids produce dose-dependant increase in left ventricular mass in power atheletes, and this effect is potentiated by concomitant use of growth hormone. Author(s): Karila TA, Karjalainen JE, Mantysaari MJ, Viitasalo MT, Seppala TA. Source: International Journal of Sports Medicine. 2003 July; 24(5): 337-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868044&dopt=Abstract
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Anabolic steroids, brain and behaviour. Author(s): Daly RC. Source: Ir Med J. 2001 April; 94(4): 102. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440042&dopt=Abstract
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Anabolic steroids. Author(s): Mottram DR, George AJ. Source: Bailliere's Best Practice & Research. Clinical Endocrinology & Metabolism. 2000 March; 14(1): 55-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10932810&dopt=Abstract
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Anabolic steroids: a review for the clinician. Author(s): Kutscher EC, Lund BC, Perry PJ. Source: Sports Medicine (Auckland, N.Z.). 2002; 32(5): 285-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929356&dopt=Abstract
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Anabolic treatment with GH, IGF-I, or anabolic steroids in patients with HIVassociated wasting. Author(s): Mulligan K, Schambelan M. Source: International Journal of Cardiology. 2002 September; 85(1): 151-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163220&dopt=Abstract
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Anabolic-androgenic steroids and related substances. Author(s): Yesalis CE, Bahrke MS. Source: Curr Sports Med Rep. 2002 August; 1(4): 246-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831702&dopt=Abstract
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Anabolic-androgenic steroids as a gateway to opioid dependence. Author(s): Arvary D, Pope HG Jr. Source: The New England Journal of Medicine. 2000 May 18; 342(20): 1532. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10819660&dopt=Abstract
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Anabolic-androgenic steroids for alcoholic liver disease. Author(s): Rambaldi A, Iaquinto G, Gluud C. Source: Cochrane Database Syst Rev. 2003; (1): Cd003045. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535450&dopt=Abstract
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Anabolic-androgenic steroids. Current issues. Author(s): Yesalis CE, Bahrke MS. Source: Sports Medicine (Auckland, N.Z.). 1995 May; 19(5): 326-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7618010&dopt=Abstract
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Anabolic-androgenic steroids: medical assessment of present, past and potential users. Author(s): O'Sullivan AJ, Kennedy MC, Casey JH, Day RO, Corrigan B, Wodak AD. Source: The Medical Journal of Australia. 2000 September 18; 173(6): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061405&dopt=Abstract
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Androgen-androgenic steroids, the athlete, and mortality. Author(s): Cotlar MJ. Source: J Insur Med. 2001; 33(3): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558405&dopt=Abstract
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Androgenic anabolic steroids and arterial structure and function in male bodybuilders. Author(s): Sader MA, Griffiths KA, McCredie RJ, Handelsman DJ, Celermajer DS. Source: Journal of the American College of Cardiology. 2001 January; 37(1): 224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153743&dopt=Abstract
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Androgens, anabolic-androgenic steroids, and inhibitors. Author(s): Donahue JL, Lowenthal DT. Source: American Journal of Therapeutics. 2000 November; 7(6): 365-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304644&dopt=Abstract
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Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis. Author(s): Korbet SM. Source: Semin Nephrol. 2003 March; 23(2): 219-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704582&dopt=Abstract
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Antenatal steroids and neonatal periventricular leukomalacia. Author(s): Canterino JC, Verma U, Visintainer PF, Elimian A, Klein SA, Tejani N. Source: Obstetrics and Gynecology. 2001 January; 97(1): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152922&dopt=Abstract
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Antenatal steroids and the developing brain. Author(s): Whitelaw A, Thoresen M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2000 September; 83(2): F154-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952714&dopt=Abstract
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Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants. Author(s): Agarwal R, Chiswick ML, Rimmer S, Taylor GM, McNally RJ, Alston RD, D'Souza SW. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 March; 86(2): F96-F101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882551&dopt=Abstract
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Antenatal steroids in twins. Author(s): Jobe AH. Source: American Journal of Obstetrics and Gynecology. 2003 March; 188(3): 856; Author Reply 857. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634674&dopt=Abstract
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Antenatal steroids to prevent respiratory distress syndrome: multiple gestation as an effect modifier. Author(s): Quist-Therson EC, Myhr TL, Ohlsson A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 May; 78(5): 388-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326882&dopt=Abstract
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Antenatal steroids: miracle drug for preemies. Author(s): Rehan VK. Source: Indian J Pediatr. 1996 September-October; 63(5): 599-608. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830028&dopt=Abstract
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Antrochonal polyp: a case report of treatment with intranasal steroids. Author(s): Seshadri R. Source: The Journal of Laryngology and Otology. 1995 June; 109(6): 553-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7643001&dopt=Abstract
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Are high-dose inhaled steroids effective for chronic obstructive pulmonary disease (COPD)? Author(s): Rosenbaum D, Merenstein D, McCormally T. Source: The Journal of Family Practice. 2000 September; 49(9): 781-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032197&dopt=Abstract
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Are weekly courses of antenatal steroids beneficial or dangerous? Author(s): Ambrus JL, Ambrus CM. Source: Jama : the Journal of the American Medical Association. 2002 January 9; 287(2): 188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779255&dopt=Abstract
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Are weekly courses of antenatal steroids beneficial or dangerous? Author(s): Murphy KE, Hannah M, Brocklehurst P. Source: Jama : the Journal of the American Medical Association. 2002 January 9; 287(2): 188; Author Reply 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779254&dopt=Abstract
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Are weekly courses of antenatal steroids beneficial or dangerous? Author(s): Jenkins TM, Wapner RJ, Thom EA, Das AF, Spong CY. Source: Jama : the Journal of the American Medical Association. 2002 January 9; 287(2): 187-8; Author Reply 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779253&dopt=Abstract
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Assessing the effect of intranasal steroids on growth. Author(s): Pedersen S. Source: The Journal of Allergy and Clinical Immunology. 2001 July; 108(1 Suppl): S40-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449205&dopt=Abstract
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Assessment of therapeutic index of inhaled steroids. Author(s): Israel E. Source: Lancet. 2000 August 12; 356(9229): 527-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950226&dopt=Abstract
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Asthma, steroids, and growth. Author(s): Wohl ME, Majzoub JA. Source: The New England Journal of Medicine. 2000 October 12; 343(15): 1113-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027747&dopt=Abstract
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Asthma: where beyond steroids? Author(s): Bertrand CP. Source: Current Opinion in Chemical Biology. 2000 August; 4(4): 407-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959768&dopt=Abstract
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Asymptomatic worsening of airway inflammation during low-dose allergen exposure in asthma: protection by inhaled steroids. Author(s): de Kluijver J, Evertse CE, Schrumpf JA, van der Veen H, Zwinderman AH, Hiemstra PS, Rabe KF, Sterk PJ. Source: American Journal of Respiratory and Critical Care Medicine. 2002 August 1; 166(3): 294-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153960&dopt=Abstract
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Automated sample preparation and gas chromatographic-mass spectrometric analysis of urinary androgenic anabolic steroids. Author(s): Haber E, Munoz-Guerra JA, Soriano C, Carreras D, Rodriguez C, Rodriguez FA. Source: J Chromatogr B Biomed Sci Appl. 2001 May 5; 755(1-2): 17-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393702&dopt=Abstract
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Avoidance of cyclosporine in renal transplantation: effects of daclizumab, mycophenolate mofetil, and steroids. Author(s): Tran HT, Acharya MK, McKay DB, Sayegh MH, Carpenter CB, Auchincloss H JR, Kirkman RL, Milford EL. Source: Journal of the American Society of Nephrology : Jasn. 2000 October; 11(10): 19039. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004222&dopt=Abstract
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Avoidance of steroids by the early use of infliximab and 6-mercaptopurine in an adolescent with active Crohn's colitis. Author(s): Persley K, Scherl E, Rubin P. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3444-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11774971&dopt=Abstract
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Beliefs about steroids: user vs. non-user comparisons. Author(s): Schwerin MJ, Corcoran KJ. Source: Drug and Alcohol Dependence. 1996 March; 40(3): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8861400&dopt=Abstract
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Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids. Author(s): Grootendorst DC, Dahlen SE, Van Den Bos JW, Duiverman EJ, VeselicCharvat M, Vrijlandt EJ, O'Sullivan S, Kumlin M, Sterk PJ, Roldaan AC. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2001 March; 31(3): 400-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260151&dopt=Abstract
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Benign giant-cell tumor of bone with metastasis to mediastinal lymph nodes. A case report of resection facilitated with use of steroids. Author(s): Lewis JJ, Healey JH, Huvos AG, Burt M. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 January; 78(1): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8550667&dopt=Abstract
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Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma. Author(s): Eisner MD, Lieu TA, Chi F, Capra AM, Mendoza GR, Selby JV, Blanc PD. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 February; 17(2): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334125&dopt=Abstract
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Beyond performance enhancement: polypharmacy among collegiate users of steroids. Author(s): Meilman PW, Crace RK, Presley CA, Lyerla R. Source: Journal of American College Health : J of Ach. 1995 November; 44(3): 98-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8543731&dopt=Abstract
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Bilateral central serous chorioretinopathy in a patient treated with systemic corticosteroids for non-Hodgkin lymphoma. Author(s): Bandello F, Incorvaia C, Rosa N, Parmeggiani F, Costagliola C, Sebastiani A. Source: Eur J Ophthalmol. 2002 March-April; 12(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022284&dopt=Abstract
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Bilateral distal biceps tendon avulsions with use of anabolic steroids. Author(s): Visuri T, Lindholm H. Source: Medicine and Science in Sports and Exercise. 1994 August; 26(8): 941-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7968426&dopt=Abstract
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Bilateral rupture of the quadriceps tendon associated with anabolic steroids. Author(s): Liow RY, Tavares S. Source: British Journal of Sports Medicine. 1995 June; 29(2): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7551764&dopt=Abstract
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Binding of ovarian steroids to erythrocytes in patients with sickle cell disease; effects on cell sickling and osmotic fragility. Author(s): Yoong WC, Tuck SM, Michael AE. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 January; 84(1): 71-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648526&dopt=Abstract
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Bioactive steroids from the brown alga Sargassum carpophyllum. Author(s): Tang HF, Yang-Hua Y, Yao XS, Xu QZ, Zhang SY, Lin HW. Source: Journal of Asian Natural Products Research. 2002 June; 4(2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067165&dopt=Abstract
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Bioassay of steroids. Author(s): Stempel DA. Source: Clinical Pharmacology and Therapeutics. 1996 April; 59(4): 482-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8612396&dopt=Abstract
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Bioavailability of orally administered sex steroids used in oral contraception and hormone replacement therapy. Author(s): Fotherby K. Source: Contraception. 1996 August; 54(2): 59-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8842581&dopt=Abstract
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Biological esterification of steroids. Author(s): Hochberg RB. Source: Endocrine Reviews. 1998 June; 19(3): 331-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9626557&dopt=Abstract
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Bleeding arising from the use of exogenous steroids. Author(s): Fraser IS. Source: Bailliere's Best Practice & Research. Clinical Obstetrics & Gynaecology. 1999 June; 13(2): 203-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755038&dopt=Abstract
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Body composition and gonadal steroids in older white and black women. Author(s): Kleerekoper M, Nelson DA, Peterson EL, Wilson PS, Jacobsen G, Longcope C. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 September; 79(3): 775-9. Erratum In: J Clin Endocrinol Metab 1995 May; 80(5): 1540. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8077360&dopt=Abstract
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Body composition and growth in asthmatic children treated with inhaled steroids. Author(s): Salvatoni A, Nosetti L, Broggini M, Nespoli L. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2000 September; 85(3): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11030277&dopt=Abstract
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Body composition, cardiovascular risk factors and liver function in long-term androgenic-anabolic steroids using bodybuilders three months after drug withdrawal. Author(s): Hartgens F, Kuipers H, Wijnen JA, Keizer HA. Source: International Journal of Sports Medicine. 1996 August; 17(6): 429-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8884417&dopt=Abstract
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Body composition, sex steroids, IGF-1, and bone mineral status in aging men. Author(s): Ravaglia G, Forti P, Maioli F, Nesi B, Pratelli L, Cucinotta D, Bastagli L, Cavalli G. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2000 September; 55(9): M516-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10995049&dopt=Abstract
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Bone densitometry, steroids and osteoporosis. Author(s): Blake GM, Fogelman I. Source: Current Opinion in Nephrology and Hypertension. 2002 November; 11(6): 641-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394611&dopt=Abstract
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Bone mineral density, sex steroids, and mineral metabolism in premenopausal smokers. Author(s): Ortego-Centeno N, Munoz-Torres M, Hernandez-Quero J, Jurado-Duce A, de la Higuera Torres-Puchol J. Source: Calcified Tissue International. 1994 December; 55(6): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7895176&dopt=Abstract
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Brain stem auditory evoked potentials: effects of ovarian steroids correlated with increased incidence of Bell's palsy in pregnancy. Author(s): Ben David Y, Tal J, Podoshin L, Fradis M, Sharf M, Pratt H, Faraggi D. Source: Otolaryngology and Head and Neck Surgery. 1995 July; 113(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7603718&dopt=Abstract
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Budesonide substitution in Crohn's disease relieves CNS toxicity of systemic steroids. Author(s): Thomas MC, Schlup MM. Source: The Medical Journal of Australia. 1998 November 16; 169(10): 560. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9861918&dopt=Abstract
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Building your body to survive: the use of anabolic steroids for HIV therapy. Author(s): Vergel N. Source: Posit Aware. 1998 March-April; 9(2): 37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11365225&dopt=Abstract
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C16 hydroxylation of 3beta-hydroxy-delta5-steroids during the early neonatal period. Author(s): Tagawa N, Kusuda S, Kobayashi Y. Source: Biological & Pharmaceutical Bulletin. 1997 December; 20(12): 1295-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448107&dopt=Abstract
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Can oral contraceptive steroids influence the elimination of nifedipine and its primary pryidine metabolite in humans? Author(s): Balogh A, Gessinger S, Svarovsky U, Hippius M, Mellinger U, Klinger G, Hoffmann A, Oettel M. Source: European Journal of Clinical Pharmacology. 1998 November-December; 54(910): 729-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9923576&dopt=Abstract
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Canadian multicentre trial of tacrolimus/azathioprine/steroids versus tacrolimus/mycophenolate mofetil/steroids versus neoral/mycophenolate mofetil/steroids in renal transplantation. Author(s): Busque S, Shoker A, Landsberg D, McAlister V, Halloran P, Shapiro J, Peets J, Schulz M. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267285&dopt=Abstract
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Capillary gas chromatography with chemical ionization negative ion mass spectrometry in the identification of odorous steroids formed in metabolic studies of the sulphates of androsterone, DHA and 5alpha-androst-16-en-3beta-ol with human axillary bacterial isolates. Author(s): Gower DB, Mallet AI, Watkins WJ, Wallace LM, Calame JP. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1997 SeptemberOctober; 63(1-3): 81-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449209&dopt=Abstract
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Carbamazepine-induced Stevens-Johnson syndrome treated with IV steroids and IVIG. Author(s): Straussberg R, Harel L, Ben-Amitai D, Cohen D, Amir J. Source: Pediatric Neurology. 2000 March; 22(3): 231-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734256&dopt=Abstract
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Cardiotonic steroids: potential endogenous sodium pump ligands with diverse function. Author(s): Dmitrieva RI, Doris PA. Source: Experimental Biology and Medicine (Maywood, N.J.). 2002 September; 227(8): 561-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192097&dopt=Abstract
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Cardiovascular complications and anabolic steroids. Author(s): Dickerman RD, McConathy WJ, Schaller F, Zachariah NY. Source: European Heart Journal. 1996 December; 17(12): 1912. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8960437&dopt=Abstract
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Cardiovascular effects of anabolic steroids in weight-trained subjects. Author(s): Palatini P, Giada F, Garavelli G, Sinisi F, Mario L, Michieletto M, Baldo-Enzi G. Source: Journal of Clinical Pharmacology. 1996 December; 36(12): 1132-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013370&dopt=Abstract
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Cardiovascular effects of androgenic-anabolic steroids. Author(s): Melchert RB, Welder AA. Source: Medicine and Science in Sports and Exercise. 1995 September; 27(9): 1252-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8531623&dopt=Abstract
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Cardiovascular risk factors in men: The role of gonadal steroids and sex hormonebinding globulin. Author(s): Gyllenborg J, Rasmussen SL, Borch-Johnsen K, Heitmann BL, Skakkebaek NE, Juul A. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 882-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474474&dopt=Abstract
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Case report: visual loss caused by facial steroids. Author(s): Michaeli-Cohen A, Neudorfer M, Loewenstein A, Lazar M, Geyer O. Source: Can Fam Physician. 1998 November; 44: 2462-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839064&dopt=Abstract
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Cause and manner of death among users of anabolic androgenic steroids. Author(s): Thiblin I, Lindquist O, Rajs J. Source: J Forensic Sci. 2000 January; 45(1): 16-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641914&dopt=Abstract
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Cell and cytokine profiles in nasal secretions from patients with nasal polyposis: effects of topical steroids and surgical treatment. Author(s): Bolard F, Gosset P, Lamblin C, Bergoin C, Tonnel AB, Wallaert B. Source: Allergy. 2001 April; 56(4): 333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284802&dopt=Abstract
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Cellular receptors for sex steroids in human pituitary adenomas. Author(s): Jaffrain-Rea ML, Petrangeli E, Ortolani F, Fraioli B, Lise A, Esposito V, Spagnoli LG, Tamburrano G, Frati L, Gulino A. Source: The Journal of Endocrinology. 1996 November; 151(2): 175-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8958777&dopt=Abstract
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Cervical ripening after treatment with prostaglandin E2 or antiprogestin (RU486). Possible mechanisms in relation to gonadal steroids. Author(s): Stjernholm YM, Sahlin L, Eriksson HA, Bystrom BE, Stenlund PM, Ekman GE. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1999 May; 84(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10413233&dopt=Abstract
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Chalazion therapy. Intralesional steroids versus incision and curettage. Author(s): Khurana AK, Ahluwalia BK, Rajan C. Source: Acta Ophthalmol (Copenh). 1988 June; 66(3): 352-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994460&dopt=Abstract
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Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts. Author(s): Laudat A, Blum L, Guechot J, Picard O, Cabane J, Imbert JC, Giboudeau J. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1995 October; 133(4): 418-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581964&dopt=Abstract
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Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition. Author(s): Shibata Y, Ito K, Suzuki K, Nakano K, Fukabori Y, Suzuki R, Kawabe Y, Honma S, Yamanaka H. Source: The Prostate. 2000 January; 42(1): 45-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10579798&dopt=Abstract
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Characterization of the rat Star gene that encodes the predominant 3.5-kilobase pair mRNA. ACTH stimulation of adrenal steroids in vivo precedes elevation of Star mRNA and protein. Author(s): Ariyoshi N, Kim YC, Artemenko I, Bhattacharyya KK, Jefcoate CR. Source: The Journal of Biological Chemistry. 1998 March 27; 273(13): 7610-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9516465&dopt=Abstract
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Chemosensitizing steroids: glucocorticoid receptor agonists capable of inhibiting Pglycoprotein function. Author(s): Gruol DJ, Bourgeois S. Source: Cancer Research. 1997 February 15; 57(4): 720-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9044851&dopt=Abstract
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Chronology of hemodynamic changes in asymptomatic in vitro fertilization patients and relationship with ovarian steroids and cytokines. Author(s): Manau D, Arroyo V, Jimenez W, Fabregues F, Vanrell JA, Balasch J. Source: Fertility and Sterility. 2002 June; 77(6): 1178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057725&dopt=Abstract
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Circulating ovarian steroids and endometrial matrix metalloproteinases (MMPs). Author(s): Henriet P, Cornet PB, Lemoine P, Galant C, Singer CF, Courtoy PJ, Eeckhout Y, Marbaix E. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 119-38; Discussion 157-8, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949942&dopt=Abstract
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Clinical applications of gas chromatography and gas chromatography-mass spectrometry of steroids. Author(s): Wolthers BG, Kraan GP. Source: J Chromatogr A. 1999 May 28; 843(1-2): 247-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399855&dopt=Abstract
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Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis. Author(s): Furue M, Terao H, Rikihisa W, Urabe K, Kinukawa N, Nose Y, Koga T. Source: The British Journal of Dermatology. 2003 January; 148(1): 128-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534606&dopt=Abstract
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Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Author(s): Jonasson G, Carlsen KH, Blomqvist P. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 November; 12(5): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9864004&dopt=Abstract
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Clinical review 107: Role of gonadal steroids in the sexual dimorphisms in body composition and circulating concentrations of leptin. Author(s): Rosenbaum M, Leibel RL. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 June; 84(6): 1784-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372664&dopt=Abstract
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CNS effects and abuse liability of anabolic-androgenic steroids. Author(s): Lukas SE. Source: Annual Review of Pharmacology and Toxicology. 1996; 36: 333-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8725393&dopt=Abstract
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Coadministration of either cyclosporine or steroids with humanized monoclonal antibodies against CD80 and CD86 successfully prolong allograft survival after life supporting renal transplantation in cynomolgus monkeys. Author(s): Hausen B, Klupp J, Christians U, Higgins JP, Baumgartner RE, Hook LE, Friedrich S, Celnicker A, Morris RE. Source: Transplantation. 2001 September 27; 72(6): 1128-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579312&dopt=Abstract
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Cognitive effects of short-term manipulation of serum sex steroids in healthy young men. Author(s): Cherrier MM, Anawalt BD, Herbst KL, Amory JK, Craft S, Matsumoto AM, Bremner WJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 July; 87(7): 3090-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107206&dopt=Abstract
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Cognitive functions and sex steroids. Author(s): Wolf OT. Source: Annales D'endocrinologie. 2003 April; 64(2): 158-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773955&dopt=Abstract
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Collagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids. Author(s): Crowley S, Trivedi P, Risteli L, Risteli J, Hindmarsh PC, Brook CG. Source: The Journal of Pediatrics. 1998 March; 132(3 Pt 1): 409-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9544892&dopt=Abstract
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Coma associated with scleromyxoedema and interferon alfa therapy. Full recovery after steroids and cyclophosphamide combined with plasmapheresis. Author(s): Rongioletti F, Hazini A, Rebora A. Source: The British Journal of Dermatology. 2001 June; 144(6): 1283-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422070&dopt=Abstract
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Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study. Author(s): Spahr L, Rubbia-Brandt L, Frossard JL, Giostra E, Rougemont AL, Pugin J, Fischer M, Egger H, Hadengue A. Source: Journal of Hepatology. 2002 October; 37(4): 448-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217597&dopt=Abstract
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Combination therapy of tacrolimus (FK506) with azathioprine and steroids in renal transplant recipients. Author(s): Yoshimura N, Oka T, Ohmori Y, Yasumura T, Nakai I, Hamashima T, Nakajima H, Okamoto M, Nakamura K, Mizuta N. Source: Transplantation Proceedings. 1998 February; 30(1): 33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474949&dopt=Abstract
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Combined treatment of a proliferative peri-orbital haemangioma with a tuneable dye laser and intra-lesional steroids to prevent deprivation amblyopia. Author(s): Gorst CM, Munnoch DA, Hancock K. Source: Journal of the Royal College of Surgeons of Edinburgh. 2001 August; 46(4): 2346. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11523716&dopt=Abstract
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Combined treatment with steroids and azathioprine in IgA nephropathy: design of a prospective randomised multicentre trial. Author(s): Locatelli F, Pozzi C, Del Vecchio L, Andrulli S, Pani A, Fogazzi G, Altieri P, Ponticelli C. Source: Journal of Nephrology. 1999 September-October; 12(5): 308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630693&dopt=Abstract
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Comparative effect of the calcium antagonist verapamil and the synthetic steroids gestrinone and danazol on human monocyte phagocytosis in vitro. Author(s): Magri B, Vigano P, Rossi G, Somigliana E, Gaffuri B, Vignali M. Source: Gynecologic and Obstetric Investigation. 1997; 43(1): 6-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9015691&dopt=Abstract
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Comparative study of phototherapy (UVB) vs. photochemotherapy (PUVA) vs. topical steroids in the treatment of primary cutaneous lichen amyloidosis. Author(s): Jin AG, Por A, Wee LK, Kai CK, Leok GC. Source: Photodermatology, Photoimmunology & Photomedicine. 2001 February; 17(1): 42-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169176&dopt=Abstract
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Comparative trial of steroids and surgical intervention in the management of ulnar neuritis. Author(s): Ebenezer M, Andrews P, Solomon S. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 1996 September; 64(3): 282-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8862262&dopt=Abstract
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Compared interest between hair analysis and urinalysis in doping controls. Results for amphetamines, corticosteroids and anabolic steroids in racing cyclists. Author(s): Gaillard Y, Vayssette F, Pepin G. Source: Forensic Science International. 2000 January 10; 107(1-3): 361-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10689587&dopt=Abstract
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Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis. Author(s): Panes J, Esteve M, Cabre E, Hinojosa J, Andreu M, Sans M, FernandezBanares F, Feu F, Gassull MA, Pique JM. Source: Gastroenterology. 2000 October; 119(4): 903-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040177&dopt=Abstract
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Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Author(s): Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Source: Thorax. 2000 October; 55(10): 837-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992535&dopt=Abstract
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Comparison of in vitro antiproliferative effects of steroids and nonsteroidal antiinflammatory drugs on human keratocytes. Author(s): Lu KL, Wee WR, Sakamoto T, McDonnell PJ. Source: Cornea. 1996 March; 15(2): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8925667&dopt=Abstract
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Comparison of inhaled beclometasone and budesonide. Back titration of inhaled steroids is uncommon in New Zealand. Author(s): Black P. Source: Bmj (Clinical Research Ed.). 1999 July 10; 319(7202): 125; Author Reply 126. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465593&dopt=Abstract
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Comparison of salmeterol with beclomethasone in adult patients with mild persistent asthma who are already on low-dose inhaled steroids. Author(s): Vermetten FA, Boermans AJ, Luiten WD, Mulder PG, Vermue NA. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 1999; 36(1): 97-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10077139&dopt=Abstract
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Complex interactions between sex steroids and cytokines in the human pregnant myometrium: evidence for an autocrine signaling system at term. Author(s): Hatthachote P, Gillespie JI. Source: Endocrinology. 1999 June; 140(6): 2533-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10342839&dopt=Abstract
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Complex regional pain syndrome type I induced by pacemaker implantation, with a good response to steroids and neurotropin. Author(s): Okada M, Suzuki K, Hidaka T, Shinohara T, Kataharada K, Takada K, Tanaka H, Ohsuzu F. Source: Intern Med. 2002 June; 41(6): 498-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135188&dopt=Abstract
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Concentration of sex steroids in adipose tissue after menopause. Author(s): Szymczak J, Milewicz A, Thijssen JH, Blankenstein MA, Daroszewski J. Source: Steroids. 1998 May-June; 63(5-6): 319-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618794&dopt=Abstract
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Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Author(s): Strohle A, Romeo E, Hermann B, Pasini A, Spalletta G, di Michele F, Holsboer F, Rupprecht R. Source: Biological Psychiatry. 1999 February 1; 45(3): 274-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10023501&dopt=Abstract
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Concerning the localization of steroids in centrioles and basal bodies by immunofluorescence. Author(s): Nenci I, Marchetti E. Source: The Journal of Cell Biology. 1978 February; 76(2): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10605436&dopt=Abstract
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Contact dermatitis due to topical steroids with conceivable cross reactions between topical steroid preparations. Author(s): Oh-i T. Source: The Journal of Dermatology. 1996 March; 23(3): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8935632&dopt=Abstract
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Contraception as prevention and therapy: sex steroids and the brain. Author(s): Stomati M, Genazzani AD, Petraglia F, Genazzani AR. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 1998 March; 3(1): 21-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678069&dopt=Abstract
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Contraceptive steroids influence the hemostatic activation state in healthy men. Author(s): Zitzmann M, Junker R, Kamischke A, Nieschlag E. Source: Journal of Andrology. 2002 July-August; 23(4): 503-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065457&dopt=Abstract
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Controversies in the use of antenatal steroids for fetal maturation. Author(s): Vidaeff AC, Mastrobattista JM. Source: Semin Perinatol. 2001 December; 25(6): 385-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778909&dopt=Abstract
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Controversies in the use of postnatal steroids. Author(s): Kennedy KA. Source: Semin Perinatol. 2001 December; 25(6): 397-405. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778910&dopt=Abstract
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Correlation between 21 amino acid endothelin, intrafollicular steroids and follicle size in stimulated cycles. Author(s): Plonowski A, Kaplinski AP, Radzikowska M, Borowiec M, Baranowska B. Source: Human Reproduction (Oxford, England). 1999 September; 14(9): 2323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469703&dopt=Abstract
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Correlations between mood scores, LH, adrenocortical steroids, and urine volumes in a patient with a history of postpartum depression and monthly psychotic episodes. Author(s): Birmingham MK, Barta A, Solyom L, Lehoux JG, Vecsei P. Source: Endocrine Research. 1998 August-November; 24(3-4): 595-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888544&dopt=Abstract
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Could steroids be withdrawn in renal transplant patients sequentially treated with ATG, cyclosporine, and cellcept? One-year results of a double-blind, randomized, multicenter study comparing normal dose versus low-dose and withdrawal of steroids. M 55002 French Study Group. Author(s): Lebranchu Y, Aubert P, Bayle F, Bedrossian J, Berthoux F, Bourbigot B, Buchler M, Chalopin JM, Deteix P, Glotz D, Huraut De Ligny B, Kessler M, Lang P, Lefrancois N, Le Pogamp P, Moulin B, Mourad G, Olmer M, Sraer JD, Touchard G, Toupance O, Wolf P, Puget S. Source: Transplantation Proceedings. 2000 March; 32(2): 396-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10715452&dopt=Abstract
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Cover illustration: regional sources of saponins, and their role in the development of oral contraceptive steroids. Author(s): Huxtable RJ. Source: Proc West Pharmacol Soc. 1996; 39: 1-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895952&dopt=Abstract
152 Steroids
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C-peptide and insulin, but not C19-steroids, support the predictive value of body mass index on leptin in serum of premenopausal women. Author(s): Geisthovel F, Meysing A, Brabant G. Source: Human Reproduction (Oxford, England). 1998 March; 13(3): 547-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572408&dopt=Abstract
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Critical illness myopathy, steroids, and cytochrome P450. Author(s): Riggs JE, Schochet SS Jr. Source: Archives of Neurology. 1998 December; 55(12): 1591. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9865810&dopt=Abstract
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Cross-talk between steroids and NF-kappa B: what language? Author(s): Dumont A, Hehner SP, Schmitz ML, Gustafsson JA, Liden J, Okret S, van der Saag PT, Wissink S, van der Burg B, Herrlich P, Haegeman G, De Bosscher K, Fiers W. Source: Trends in Biochemical Sciences. 1998 July; 23(7): 233-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9697408&dopt=Abstract
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CSA/MMF/steroids versus CSA/AZA/steroids with and without basiliximab in cadaveric kidney transplantation. Author(s): Boggi U, Vistoli F, Del Chiaro M, Bartolo TV, Rizzo G, Mosca F. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3199-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750372&dopt=Abstract
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Current controversies surrounding the use of repeated courses of antenatal steroids. Author(s): Lamer P. Source: Advances in Neonatal Care : Official Journal of the National Association of Neonatal Nurses. 2002 December; 2(6): 290-300; Quiz 301-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881942&dopt=Abstract
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Cushing's syndrome, growth impairment, and occult adrenal suppression associated with intranasal steroids. Author(s): Perry RJ, Findlay CA, Donaldson MD. Source: Archives of Disease in Childhood. 2002 July; 87(1): 45-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089123&dopt=Abstract
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Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial. Author(s): Zuckermann A, Reichenspurner H, Birsan T, Treede H, Deviatko E, Reichart B, Klepetko W. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 April; 125(4): 891-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698153&dopt=Abstract
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Cyclosporine-A plus steroids versus steroids alone in the 12-month treatment of systemic lupus erythematosus. Author(s): Dammacco F, Della Casa Alberighi O, Ferraccioli G, Racanelli V, Casatta L, Bartoli E. Source: International Journal of Clinical & Laboratory Research. 2000; 30(2): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043499&dopt=Abstract
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CYP17 genetic polymorphism in endometrial cancer: are only steroids involved? Author(s): Berstein LM, Imyanitov EN, Gamajunova VB, Kovalevskij AJ, Kuligina ESh, Belogubova EV, Buslov KG, Karpova MB, Togo AV, Volkov ON, Kovalenko IG. Source: Cancer Letters. 2002 June 6; 180(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911969&dopt=Abstract
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Cytotoxic cembrenolides and steroids from the formosan soft coral Sarcophyton crassocaule. Author(s): Duh CY, Wang SK, Chung SG, Chou GC, Dai CF. Source: Journal of Natural Products. 2000 December; 63(12): 1634-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11141104&dopt=Abstract
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Daclizumab induction for primary kidney transplant recipients using tacrolimus, mycophenolate mofetil, and steroids as maintenance immunosuppression. Author(s): Ciancio G, Miller A, Burke GW, Gharagozloo H, Rosen A, Roth D, Kupin W, Pinna A, Cespedes M, Esquenazi V, Miller J. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1013-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267169&dopt=Abstract
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Daclizumab induction, tacrolimus, mycophenolate mofetil and steroids as an immunosuppression regimen for primary kidney transplant recipients. Author(s): Ciancio G, Burke GW, Suzart K, Roth D, Kupin W, Rosen A, Olson L, Esquenazi V, Miller J. Source: Transplantation. 2002 April 15; 73(7): 1100-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965039&dopt=Abstract
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Decreased bone mineral density in premenopausal asthma patients receiving longterm inhaled steroids. Author(s): Ip M, Lam K, Yam L, Kung A, Ng M. Source: Chest. 1994 June; 105(6): 1722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8205866&dopt=Abstract
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Defined-formula diets versus steroids in the treatment of active Crohn's disease: a meta-analysis. Author(s): Messori A, Trallori G, D'Albasio G, Milla M, Vannozzi G, Pacini F. Source: Scandinavian Journal of Gastroenterology. 1996 March; 31(3): 267-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8833357&dopt=Abstract
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Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropinreleasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. Author(s): Valenti S, Giusti M, McGuinness D, Guido R, Mori PG, Giordano G, Dahl KD. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1995 July; 133(1): 48-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7627337&dopt=Abstract
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Despite warnings, lure of steroids too strong for some young Canadians. Author(s): Newman S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1994 September 15; 151(6): 844-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8087759&dopt=Abstract
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Detection and determination of anabolic steroids in nutritional supplements. Author(s): De Cock KJ, Delbeke FT, Van Eenoo P, Desmet N, Roels K, De Backer P. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 July; 25(5-6): 843-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377067&dopt=Abstract
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Detection of anabolic steroids in head hair. Author(s): Deng XS, Kurosu A, Pounder DJ. Source: J Forensic Sci. 1999 March; 44(2): 343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10097359&dopt=Abstract
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Detection of oestrogenic activity of steroids present during mammalian gestation using oestrogen receptor alpha- and oestrogen receptor beta-specific in vitro assays. Author(s): Lemmen JG, van den Brink CE, Legler J, van der Saag PT, van der Burg B. Source: The Journal of Endocrinology. 2002 September; 174(3): 435-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208664&dopt=Abstract
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Determinants of blood pressure in very low birth weight neonates: lack of effect of antenatal steroids. Author(s): LeFlore JL, Engle WD, Rosenfeld CR. Source: Early Human Development. 2000 July; 59(1): 37-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962166&dopt=Abstract
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Determination of anabolic steroids by gas chromatography/negative-ion chemical ionization mass spectrometry and gas chromatography/negative-ion chemical ionization tandem mass spectrometry with heptafluorobutyric anhydride derivatization. Author(s): Choi MH, Chung BC, Lee W, Lee UC, Kim Y. Source: Rapid Communications in Mass Spectrometry : Rcm. 1999; 13(5): 376-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10209875&dopt=Abstract
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Dexamethasone pulse steroids in ulcerative colitis--is it time for a change? Author(s): Patel SM, Falchuk K. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797351&dopt=Abstract
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Diagnosing and managing polymyalgia rheumatica and temporal arteritis. Patients starting steroids should be given advice on risk of osteoporosis. Author(s): Hodgkins P, Hull R. Source: Bmj (Clinical Research Ed.). 1997 August 30; 315(7107): 550. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329330&dopt=Abstract
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Diagnosing and managing polymyalgia rheumatica and temporal arteritis. Urgency in giving steroids in giant cell arteritis is still not widely appreciated. Author(s): Freeman AG. Source: Bmj (Clinical Research Ed.). 1997 August 30; 315(7107): 549-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329328&dopt=Abstract
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Differences in the potencies of inhaled steroids are not reflected in the doses prescribed in primary care in New Zealand. Author(s): Black PN, Lawrence BJ, Goh KH, Barry MS. Source: European Journal of Clinical Pharmacology. 2000 August; 56(5): 431-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11009054&dopt=Abstract
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Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. Author(s): Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Source: The New England Journal of Medicine. 1998 January 22; 338(4): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9435325&dopt=Abstract
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Differential effects of sex steroids on T and B cells: modulation of cell cycle phase distribution, apoptosis and bcl-2 protein levels. Author(s): McMurray RW, Suwannaroj S, Ndebele K, Jenkins JK. Source: Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology. 2001; 69(1): 44-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11641617&dopt=Abstract
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Differential mitogenicity of ovarian steroids on mammary explants. Author(s): van Bogaert LJ. Source: American Journal of Obstetrics and Gynecology. 1996 November; 175(5): 1393-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8942528&dopt=Abstract
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Differential modulation of the gamma-aminobutyric acid type C receptor by neuroactive steroids. Author(s): Morris KD, Moorefield CN, Amin J. Source: Molecular Pharmacology. 1999 October; 56(4): 752-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496958&dopt=Abstract
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Differential production of adrenal steroids by purified cells of the human adrenal cortex is relative rather than absolute. Author(s): Young LS, Murphy G, Kelly SN, Smith TP, Cunningham SK, Joseph McKenna T. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 January; 148(1): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534367&dopt=Abstract
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Differential regulation of gonadotropin-releasing hormone (GnRH)I and GnRHII messenger ribonucleic acid by gonadal steroids in human granulosa luteal cells. Author(s): Khosravi S, Leung PC. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 663-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574197&dopt=Abstract
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Digoxin assays: frequent, substantial, and potentially dangerous interference by spironolactone, canrenone, and other steroids. Author(s): Steimer W, Muller C, Eber B. Source: Clinical Chemistry. 2002 March; 48(3): 507-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861441&dopt=Abstract
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Direct determination of anabolic steroids in human urine by on-line solid-phase extraction/liquid chromatography/mass spectrometry. Author(s): Barron D, Barbosa J, Pascual JA, Segura J. Source: Journal of Mass Spectrometry : Jms. 1996 March; 31(3): 309-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8799280&dopt=Abstract
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Direct non-genomic effects of follicular steroids on maturing human oocytes: oestrogen versus androgen antagonism. Author(s): Tesarik J, Mendoza C. Source: Human Reproduction Update. 1997 March-April; 3(2): 95-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9286733&dopt=Abstract
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Disseminated varicella and staphylococcal pericarditis after topical steroids. Author(s): Brumund MR, Truemper EJ, Lutin WA, Pearson-Shaver AL. Source: The Journal of Pediatrics. 1997 July; 131(1 Pt 1): 162-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255210&dopt=Abstract
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Diurnal rhythm in serum levels of inhibin B in normal men: relation to testicular steroids and gonadotropins. Author(s): Carlsen E, Olsson C, Petersen JH, Andersson AM, Skakkebaek NE. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 May; 84(5): 1664-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10323397&dopt=Abstract
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Diverse actions of ovarian steroids in the serotonin neural system. Author(s): Bethea CL, Lu NZ, Gundlah C, Streicher JM. Source: Frontiers in Neuroendocrinology. 2002 January; 23(1): 41-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906203&dopt=Abstract
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DNA adduct formation by hormonal steroids in vitro. Author(s): Seraj MJ, Umemoto A, Tanaka M, Kajikawa A, Hamada K, Monden Y. Source: Mutation Research. 1996 August; 370(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8830806&dopt=Abstract
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Do anabolic-androgenic steroids enhance sporting performance? Author(s): Kennedy MC, O'Sullivan AJ. Source: The Medical Journal of Australia. 1997 January 20; 166(2): 60-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9033556&dopt=Abstract
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Do inhaled steroids have similar efficacy? A case of bronchial asthma suggesting different efficacy of inhaled glucocorticosteroids. Author(s): Larsen BB, Dahl R. Source: Allergy. 1995 July; 50(7): 600-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8588695&dopt=Abstract
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Do intravenous steroids play a role for tonsillectomy patients? Author(s): Hengerer AS. Source: Archives of Otolaryngology--Head & Neck Surgery. 2001 August; 127(8): 1010. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493218&dopt=Abstract
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Do neuroactive steroids cause fatigue in pregnancy? Author(s): Biedermann K, Schoch P. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1995 January; 58(1): 15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7758639&dopt=Abstract
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Do steroids help jaundice caused by primary sclerosing cholangitis? Author(s): Parkes M, Booth JC, Pillai G, Mee AS. Source: Journal of Clinical Gastroenterology. 2001 October; 33(4): 319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588548&dopt=Abstract
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Do steroids interfere in dyspnoea sensation? Author(s): Kallas de Carvalho F, Filho JT, Vianna EO, Silva GA, Martinez JA. Source: Respiratory Medicine. 2002 July; 96(7): 511-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194635&dopt=Abstract
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Do steroids prevent reintubation in children with laryngotracheobronchitis? Author(s): Rajah J, Riera-Fanego J, Keeton J, Ramjee A, Bhana R, Lasersohn L, Hon H. Source: Critical Care (London, England). 2000; 4(5): 314-8. Epub 2000 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056758&dopt=Abstract
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Do steroids reduce morbidity of tonsillectomy? Meta-analysis of randomized trials. Author(s): Steward DL, Welge JA, Myer CM. Source: The Laryngoscope. 2001 October; 111(10): 1712-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801931&dopt=Abstract
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Do topical steroids reduce relapses in adults with atopic dermatitis? Author(s): Williams HC. Source: Archives of Dermatology. 1999 December; 135(12): 1530-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606062&dopt=Abstract
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Dose linearity study of selegiline pharmacokinetics after oral administration: evidence for strong drug interaction with female sex steroids. Author(s): Laine K, Anttila M, Helminen A, Karnani H, Huupponen R. Source: British Journal of Clinical Pharmacology. 1999 March; 47(3): 249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215747&dopt=Abstract
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Dose-dependent effects of intranasal steroids: how relevant? Author(s): Naclerio RM. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2000 October; 85(4): 248-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061465&dopt=Abstract
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Dual regulation of the epidermal growth factor family of growth factors in breast cancer by sex steroids and protein kinase C. Author(s): Martinez-Lacaci I, Dickson RB. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1996 January; 57(12): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8645607&dopt=Abstract
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Dupuytren's disease. A model for the mechanism of fibrosis and its modulation by steroids. Author(s): Meek RM, McLellan S, Crossan JF. Source: The Journal of Bone and Joint Surgery. British Volume. 1999 July; 81(4): 732-8. Erratum In: J Bone Joint Surg Br 1999 September; 81(5): 938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463754&dopt=Abstract
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Dysphonia associated with inhaled steroids. Author(s): Lavy JA, Wood G, Rubin JS, Harries M. Source: Journal of Voice : Official Journal of the Voice Foundation. 2000 December; 14(4): 581-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130115&dopt=Abstract
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Early B-lymphocyte precursors and their regulation by sex steroids. Author(s): Kincade PW, Medina KL, Payne KJ, Rossi MI, Tudor KS, Yamashita Y, Kouro T. Source: Immunological Reviews. 2000 June; 175: 128-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933598&dopt=Abstract
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Early effects of inhaled steroids on airway hyperreactivity and pulmonary function in asthma. Author(s): Sherrington CA, Mallol J. Source: Pediatric Pulmonology. 1999 June; 27(6): 376-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10380088&dopt=Abstract
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Early introduction of inhaled steroids in wheezing children presenting in primary care. A pilot study. EASE Study Group. Author(s): Baxter-Jones AD, Helms PJ. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2000 November; 30(11): 1618-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069572&dopt=Abstract
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Effect of androgenic anabolic steroids on semen parameters and hormone levels in bodybuilders. Author(s): Torres-Calleja J, De Celis R, Gonzalez-Unzaga M, Pedron-Nuevo N. Source: Fertility and Sterility. 2000 November; 74(5): 1055-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056262&dopt=Abstract
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Effect of androgenic anabolic steroids on sperm quality and serum hormone levels in adult male bodybuilders. Author(s): Torres-Calleja J, Gonzalez-Unzaga M, DeCelis-Carrillo R, Calzada-Sanchez L, Pedron N. Source: Life Sciences. 2001 March 2; 68(15): 1769-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270623&dopt=Abstract
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Effect of antenatal steroids on lung maturity and brain development. Author(s): Santhanakrishnan BR. Source: Indian Pediatrics. 2000 December; 37(12): 1390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119353&dopt=Abstract
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Effect of female sex steroids on human endometrial CD16neg CD56bright natural killer cells. Author(s): Kitaya K, Yasuda J, Nakayama T, Fushiki S, Honjo H. Source: Fertility and Sterility. 2003 March; 79 Suppl 1: 730-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620484&dopt=Abstract
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Effect of immunosuppressive agents FK 506 and cyclosporin and steroids on the expression of IL-6 and its receptor by stimulated lymphocytes and monocytes. Author(s): Moutabarrik A, Nakanishi I, Takahara S, Hachim K, Bengahnem MG, Ramadani B, Ishibashi M, Zaid D. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7 Suppl 1: S552-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271305&dopt=Abstract
Studies 161
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Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma. Author(s): van Rensen EL, Straathof KC, Veselic-Charvat MA, Zwinderman AH, Bel EH, Sterk PJ. Source: Thorax. 1999 May; 54(5): 403-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10212103&dopt=Abstract
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Effect of inhaled steroids on bone mineral density: a meta-analysis. Author(s): Sharma PK, Malhotra S, Pandhi P, Kumar N. Source: Journal of Clinical Pharmacology. 2003 February; 43(2): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616673&dopt=Abstract
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Effect of low birth weight on adrenal steroids and carbohydrate metabolism in early adulthood. Author(s): Szathmari M, Vasarhelyi B, Tulassay T. Source: Hormone Research. 2001; 55(4): 172-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598370&dopt=Abstract
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Effect of prenatal steroids on potassium balance in extremely low birth weight neonates. Author(s): Omar SA, DeCristofaro JD, Agarwal BI, LaGamma EF. Source: Pediatrics. 2000 September; 106(3): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969103&dopt=Abstract
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Effect of sex steroids on beta-endorphin levels at rest and during submaximal treadmill exercise in anovulatory and ovulatory runners. Author(s): Meyer WR, Muoio D, Hackney TC. Source: Fertility and Sterility. 1999 June; 71(6): 1085-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360915&dopt=Abstract
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Effect of sirolimus in combination with low-dose cyclosporine and steroids on acute renal allograft rejection. Author(s): Tsai MK, Chueh SC, Hu RH, Lee PH. Source: J Formos Med Assoc. 2003 February; 102(2): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709737&dopt=Abstract
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Effect of steroids amount on hepatitis C recurrence following orthtopic liver transplantation. Author(s): Tisone G, Laria G, Orlando G, Pisani F, Palmieri GP, Bellanova G, Torri E, Buonomo O, Angelico M, Casciani CU. Source: Transplantation Proceedings. 1999 December; 31(8): 3167-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616427&dopt=Abstract
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Effect of steroids on arterial Doppler in intrauterine growth retardation fetuses. Author(s): Senat MV, Ville Y. Source: Fetal Diagnosis and Therapy. 2000 January-February; 15(1): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705212&dopt=Abstract
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Effect of steroids on energy expenditure and substrate oxidation in women with Crohn's disease. Author(s): Al-Jaouni R, Schneider SM, Piche T, Rampal P, Hebuterne X. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2843-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425558&dopt=Abstract
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Effect of steroids on posttonsillectomy pain in adults. Author(s): Carr MM, Williams JG, Carmichael L, Nasser JG. Source: Archives of Otolaryngology--Head & Neck Surgery. 1999 December; 125(12): 1361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10604415&dopt=Abstract
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Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine. Author(s): Bicikova M, Tallova J, Hill M, Vanuga A, Putz Z, Tomandl J. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2001 August; 39(8): 753-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592446&dopt=Abstract
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Effectiveness of adjunctive treatment with steroids in reducing short-term mortality in a high-risk population of children with bacterial meningitis. Author(s): Ciana G, Parmar N, Antonio C, Pivetta S, Tamburlini G, Cuttini M. Source: Journal of Tropical Pediatrics. 1995 June; 41(3): 164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7636936&dopt=Abstract
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Effectiveness of multidose antenatal steroids. Author(s): Elimian A, Verma U, Visintainer P, Tejani N. Source: Obstetrics and Gynecology. 2000 January; 95(1): 34-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636498&dopt=Abstract
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Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase. Author(s): Fisher A, Friel EC, Bernhardt R, Gomez-Sanchez C, Connell JM, Fraser R, Davies E. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 September; 86(9): 4326-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549669&dopt=Abstract
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Effects of adding steroids, in vitro irradiation, or both to cyclosporine immunosuppression in the murine laryngeal transplantation model. Author(s): Lorenz RR, Dan O, Haug M 3rd, Strome M. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 May; 111(5 Pt 1): 4559. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019516&dopt=Abstract
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Effects of age, sex steroids, and family relationships on volumes of prostate zones in men with and without prostate cancer. Author(s): Meikle AW, Stephenson RA, McWhorter WP, Skolnick MH, Middleton RG. Source: The Prostate. 1995 May; 26(5): 253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7753710&dopt=Abstract
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Effects of anabolic steroids on the muscle cells of strength-trained athletes. Author(s): Kadi F, Eriksson A, Holmner S, Thornell LE. Source: Medicine and Science in Sports and Exercise. 1999 November; 31(11): 1528-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589853&dopt=Abstract
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Effects of anabolic-androgenic steroids on weight-lifters' myocardium: an ultrasonic videodensitometric study. Author(s): Di Bello V, Giorgi D, Bianchi M, Bertini A, Caputo MT, Valenti G, Furioso O, Alessandri L, Paterni M, Giusti C. Source: Medicine and Science in Sports and Exercise. 1999 April; 31(4): 514-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211845&dopt=Abstract
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Effects of antenatal steroids on the complications of prematurity in an era of surfactant replacement therapy in Oman. Author(s): da Costa DE, Nair PA, Al Khusaiby SM. Source: Journal of Tropical Pediatrics. 2000 December; 46(6): 375-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11191153&dopt=Abstract
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Effects of Duraflo II heparin-coated cardiopulmonary bypass circuits on the coagulation system, endothelial damage, and cytokine release in patients with cardiac operation employing aprotinin and steroids. Author(s): Inui K, Shimazaki Y, Watanabe T, Takahashi T, Minowa T, Takeda H, Yanagawa N, Sotoda Y. Source: Artificial Organs. 1999 December; 23(12): 1107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619929&dopt=Abstract
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Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes. Author(s): Nakamura H, Nakasa H, Ishii I, Ariyoshi N, Igarashi T, Ohmori S, Kitada M. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 May; 30(5): 534-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950784&dopt=Abstract
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Effects of exposing the opened endolymphatic sac to large doses of steroids to treat intractable Meniere's disease. Author(s): Kitahara T, Takeda N, Mishiro Y, Saika T, Fukushima M, Okumura S, Kubo T. Source: The Annals of Otology, Rhinology, and Laryngology. 2001 February; 110(2): 10912. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219515&dopt=Abstract
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Effects of female sex steroids on Parkinson's disease in postmenopausal women. Author(s): Strijks E, Kremer JA, Horstink MW. Source: Clinical Neuropharmacology. 1999 March-April; 22(2): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202604&dopt=Abstract
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Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls. Author(s): Daly RC, Schmidt PJ, Davis CL, Danaceau MA, Rubinow DR. Source: Psychoneuroendocrinology. 2001 August; 26(6): 539-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403976&dopt=Abstract
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Effects of house dust mite avoidance measures on Der p 1 concentrations and clinical condition of mild adult house dust mite-allergic asthmatic patients, using no inhaled steroids. Author(s): Cloosterman SG, Schermer TR, Bijl-Hofland ID, Van Der Heide S, Brunekreef B, Van Den Elshout FJ, Van Herwaarden CL, Van Schayck CP. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 October; 29(10): 1336-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10520054&dopt=Abstract
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Effects of inhalation of steroids on lung permeability in patients with asthma. Author(s): Wang SJ, Kao CH, Lin WY, Hsu CY, Chang CP, Lan JL. Source: Clinical Nuclear Medicine. 1995 June; 20(6): 494-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7648729&dopt=Abstract
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Effects of inhaled steroids on methacholine-induced bronchoconstriction and gas trapping in mild asthma. Author(s): Corsico A, Pellegrino R, Zoia MC, Barbano L, Brusasco V, Cerveri I. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 April; 15(4): 687-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780760&dopt=Abstract
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Effects of laparoscopic ovarian drilling on adrenal steroids in polycystic ovary syndrome patients with and without hyperinsulinemia. Author(s): Saleh A, Morris D, Tan SL, Tulandi T. Source: Fertility and Sterility. 2001 March; 75(3): 501-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239531&dopt=Abstract
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Effects of multiple courses of antenatal steroids are uncertain. Author(s): Brocklehurst P, Gates S, Johnson A, Alfirevic Z, Chamberlain G. Source: Bmj (Clinical Research Ed.). 2000 July 1; 321(7252): 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10939812&dopt=Abstract
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Effects of oral steroids on blood CXCR3+ and CCR4+ T cells in patients with bronchial asthma. Author(s): Kurashima K, Fujimura M, Myou S, Kasahara K, Tachibana H, Amemiya N, Ishiura Y, Onai N, Matsushima K, Nakao S. Source: American Journal of Respiratory and Critical Care Medicine. 2001 September 1; 164(5): 754-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549528&dopt=Abstract
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Effects of prenatal steroids on water and sodium homeostasis in extremely low birth weight neonates. Author(s): Omar SA, DeCristofaro JD, Agarwal BI, La Gamma EF. Source: Pediatrics. 1999 September; 104(3 Pt 1): 482-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469773&dopt=Abstract
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Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Author(s): Elbers JM, Giltay EJ, Teerlink T, Scheffer PG, Asscheman H, Seidell JC, Gooren LJ. Source: Clinical Endocrinology. 2003 May; 58(5): 562-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699437&dopt=Abstract
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Effects of sex steroids on sleep. Author(s): Empson JA, Purdie DW. Source: Annals of Medicine. 1999 April; 31(2): 141-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10344587&dopt=Abstract
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Effects of sex steroids on survival and receptor expression in ovarian epithelial tumour cells. Author(s): Taube M, Hockenstrom T, Isaksson M, Lindgren PR, Backstrom T. Source: International Journal of Oncology. 2003 June; 22(6): 1257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738991&dopt=Abstract
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Effects of transdermal application of DHEA on the levels of steroids, gonadotropins and lipids in men. Author(s): Sulcova J, Hill M, Hampl R, Masek Z, Novacek A, Ceska R, Starka L. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2000; 49(6): 685-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11252535&dopt=Abstract
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Effects of various steroids on platelet-derived endothelial cell growth factor (PDECGF) and its mRNA expression in uterine endometrial cancer cells. Author(s): Aoki I, Fujimoto J, Tamaya T. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711006&dopt=Abstract
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Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction. Author(s): O'Brien A, Russo-Magno P, Karki A, Hiranniramol S, Hardin M, Kaszuba M, Sherman C, Rounds S. Source: American Journal of Respiratory and Critical Care Medicine. 2001 August 1; 164(3): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11500334&dopt=Abstract
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Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide. Author(s): Ferguson AC, Spier S, Manjra A, Versteegh FG, Mark S, Zhang P. Source: The Journal of Pediatrics. 1999 April; 134(4): 422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10190915&dopt=Abstract
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Efficacy of epidural steroids in low back pain and sciatica. A critical appraisal by a French Task Force of randomized trials. Critical Analysis Group of the French Society for Rheumatology. Author(s): Rozenberg S, Dubourg G, Khalifa P, Paolozzi L, Maheu E, Ravaud P. Source: Rev Rhum Engl Ed. 1999 February; 66(2): 79-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084166&dopt=Abstract
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Electron-capturing derivatization of neutral steroids for increasing sensitivity in liquid chromatography/negative atmospheric pressure chemical ionization-mass spectrometry. Author(s): Higashi T, Takido N, Yamauchi A, Shimada K. Source: Anal Sci. 2002 December; 18(12): 1301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502079&dopt=Abstract
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Elevation of serum IGF-1 rather than sex steroids precedes proliferative diabetic retinopathy in Mauriac's syndrome. Author(s): Chantelau E, Seppel T, Althaus C, Schonau E. Source: Hormone Research. 1997; 48(3): 131-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11546930&dopt=Abstract
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EMS mythology, Part 5. EMS myth #5: Steroids are effective in the treatment of acute spinal cord injury. Author(s): Bledsoe BE. Source: Emerg Med Serv. 2003 July; 32(7): 92-3, 95. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889431&dopt=Abstract
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Enantiomeric steroids: synthesis, physical, and biological properties. Author(s): Biellmann JF. Source: Chemical Reviews. 2003 May; 103(5): 2019-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744699&dopt=Abstract
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Endogenous cardiotonic steroids. Author(s): Schoner W. Source: Cell Mol Biol (Noisy-Le-Grand). 2001 March; 47(2): 273-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355001&dopt=Abstract
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Energetic factors, ovarian steroids and the risk of breast cancer. Author(s): Jasienska G, Thune I, Ellison PT. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2000 August; 9(4): 231-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958326&dopt=Abstract
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Eosinophilic fasciitis responsive to treatment with pulsed steroids and cyclosporine. Author(s): Valencia IC, Chang A, Kirsner RS, Kerdel FA. Source: International Journal of Dermatology. 1999 May; 38(5): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10369548&dopt=Abstract
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Epidural steroids as a pharmacological approach. Author(s): Reale C, Turkiewicz AM, Reale CA, Stabile S, Borgonuovo P, Apponi F. Source: Clin Exp Rheumatol. 2000 March-April; 18(2 Suppl 19): S65-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10824290&dopt=Abstract
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Epidural steroids. Author(s): Mulligan KA, Rowlingson JC. Source: Current Pain and Headache Reports. 2001 December; 5(6): 495-502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676883&dopt=Abstract
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Ergosteroids VII: perchloric acid-induced transformations of 7-oxygenated steroids and their bio-analytical applications--a liquid chromatographic-mass spectrometric study. Author(s): Marwah A, Marwah P, Lardy H. Source: Bioorganic Chemistry. 2002 August; 30(4): 233-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392703&dopt=Abstract
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Esophageal lipomatosis: another consequence of the use of steroids. Author(s): Bogaert J, Rosseel F, Verhaegen S, Verschakelen J. Source: European Radiology. 2000; 10(9): 1390-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997425&dopt=Abstract
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Evaluation of aminotransferase elevations in a bodybuilder using anabolic steroids: hepatitis or rhabdomyolysis? Author(s): Pertusi R, Dickerman RD, McConathy WJ. Source: J Am Osteopath Assoc. 2001 July; 101(7): 391-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476029&dopt=Abstract
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Evaluation of the effects of zafirlukast 40 mg b.i.d. in addition to preexisting therapy of high-dose inhaled steroids on symptomatic patients with reversible respiratory obstruction: preliminary data. Author(s): Centanni S, Santus P, Casanova F, Di Marco F, Brazzola G, Canonica GW. Source: Drugs Exp Clin Res. 2000; 26(4): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109513&dopt=Abstract
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Evidence of differential control of FSH and LH responses to GnRH by ovarian steroids in the luteal phase of the cycle. Author(s): Messinis IE, Milingos S, Alexandris E, Mademtzis I, Kollios G, Seferiadis K. Source: Human Reproduction (Oxford, England). 2002 February; 17(2): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821267&dopt=Abstract
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Examination on biological activities and fates of new steroids, steroid-17-yl methyl glycolate derivatives. Author(s): Suzuki T, Tada H, Sato E, Tojima Y. Source: The Tohoku Journal of Experimental Medicine. 1999 February; 187(2): 127-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10228984&dopt=Abstract
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Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids. Author(s): Braseth NR, Allison EJ Jr, Gough JE. Source: European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. 2001 June; 8(2): 155-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436915&dopt=Abstract
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Exhaled nitric oxide, sensitization, and exposure to allergens in patients with asthma who are not taking inhaled steroids. Author(s): Simpson A, Custovic A, Pipis S, Adisesh A, Faragher B, Woodcock A. Source: American Journal of Respiratory and Critical Care Medicine. 1999 July; 160(1): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10390378&dopt=Abstract
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Expression of Gsalpha, connexin-43, connexin-26, and EP1, 3, and 4 receptors in myometrium of prelabor singleton versus multiple gestations and the effects of mechanical stretch and steroids on Gsalpha. Author(s): Lyall F, Lye S, Teoh T, Cousins F, Milligan G, Robson S. Source: Journal of the Society for Gynecologic Investigation. 2002 September-October; 9(5): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383915&dopt=Abstract
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Expression of matrix metalloprotease-2-cleaved laminin-5 in breast remodeling stimulated by sex steroids. Author(s): Giannelli G, Pozzi A, Stetler-Stevenson WG, Gardner HA, Quaranta V. Source: American Journal of Pathology. 1999 April; 154(4): 1193-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10233857&dopt=Abstract
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Expression of RFG/ELE1alpha/ARA70 in normal and malignant prostatic epithelial cell cultures and lines: regulation by methylation and sex steroids. Author(s): Tekur S, Lau KM, Long J, Burnstein K, Ho SM. Source: Molecular Carcinogenesis. 2001 January; 30(1): 1-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255259&dopt=Abstract
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Exquisitely small amounts of nonglucocorticoid natural steroids suppress the human allogeneic T-cell response. Author(s): Terness P, Navolan D, Dufter C, Kopp B, Opelz G. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 547-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266951&dopt=Abstract
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Extra-fine particles improve lung delivery of inhaled steroids in infants: a study in an upper airway model. Author(s): Janssens HM, De Jongste JC, Hop WC, Tiddens HA. Source: Chest. 2003 June; 123(6): 2083-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796192&dopt=Abstract
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Extragonadal synthesis of sex steroids: intracrinology. Author(s): Labrie F. Source: Annales D'endocrinologie. 2003 April; 64(2): 95-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773942&dopt=Abstract
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Faces, hips, and steroids. Author(s): Habal MB. Source: Plastic and Reconstructive Surgery. 1995 March; 95(3): 614. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7870809&dopt=Abstract
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Factors associated with adolescent use of doping agents: anabolic-androgenic steroids. Author(s): Kindlundh AM, Isacson DG, Berglund L, Nyberg F. Source: Addiction (Abingdon, England). 1999 April; 94(4): 543-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10605850&dopt=Abstract
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Faecal steroids and colorectal carcinogenesis. Author(s): Owen RW. Source: Scand J Gastroenterol Suppl. 1997; 222: 76-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145454&dopt=Abstract
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Failure to demonstrate therapeutic tachyphylaxis to topically applied steroids in patients with psoriasis. Author(s): Miller JJ, Roling D, Margolis D, Guzzo C. Source: Journal of the American Academy of Dermatology. 1999 October; 41(4): 546-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10495373&dopt=Abstract
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False-negative single-photon emission CT in AIDS lymphoma: lack of effect of steroids. Author(s): Campbell BG, Hurley J, Zimmerman RD. Source: Ajnr. American Journal of Neuroradiology. 1996 May; 17(5): 1000-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8733980&dopt=Abstract
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Fast screening of anabolic steroids and other banned doping substances in human urine by gas chromatography/tandem mass spectrometry. Author(s): Marcos J, Pascual JA, de la Torre X, Segura J. Source: Journal of Mass Spectrometry : Jms. 2002 October; 37(10): 1059-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375280&dopt=Abstract
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Fatal chickenpox pneumonia in an asthmatic patient on oral steroids and methotrexate. Author(s): Gatnash AA, Connolly CK. Source: Thorax. 1995 April; 50(4): 422-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7785019&dopt=Abstract
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Fatal invasive aspergillosis during cyclosporine and steroids treatment for Crohn's disease. Author(s): Scalzini A, Barni C, Stellini R, Sueri L. Source: Digestive Diseases and Sciences. 1995 March; 40(3): 528. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7895537&dopt=Abstract
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Fatal leukoencephalopathy in a patient with non-Hodgkin's lymphoma treated with CHOP chemotherapy and high-dose steroids. Author(s): Cain MS, Burton GV, Holcombe RF. Source: The American Journal of the Medical Sciences. 1998 March; 315(3): 202-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9519935&dopt=Abstract
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Fatal myocardial infarction in an elderly woman with severe ulcerative colitis: what is the role of steroids? Author(s): Baty V, Blain H, Saadi L, Jeandel C, Canton P. Source: The American Journal of Gastroenterology. 1998 October; 93(10): 2000-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9772083&dopt=Abstract
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Fat-free mass index in users and nonusers of anabolic-androgenic steroids. Author(s): Kouri EM, Pope HG Jr, Katz DL, Oliva P. Source: Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine. 1995 October; 5(4): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7496846&dopt=Abstract
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Fecal steroids of the coprolite of a Greenland Eskimo mummy, AD 1475: a clue to dietary sterol intake. Author(s): Lin DS, Connor WE. Source: The American Journal of Clinical Nutrition. 2001 July; 74(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451716&dopt=Abstract
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Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IVIgG and steroids. Author(s): Summerfield GP, Beeby A, Bosman D, Chapman C. Source: British Journal of Haematology. 1998 September; 102(5): 1380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9753075&dopt=Abstract
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Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids--more questions than answers. European Working Group on FMAIT. Author(s): Kaplan C, Murphy MF, Kroll H, Waters AH. Source: British Journal of Haematology. 1998 January; 100(1): 62-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9450792&dopt=Abstract
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Fever and leucopenia with steroids. Author(s): Maeshima E, Yamada Y, Yukawa S. Source: Lancet. 2000 January 15; 355(9199): 198. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10675120&dopt=Abstract
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First results from a prospective randomized trial comparing steroid-free induction therapy with tacrolimus and MMF versus tacrolimus and steroids in patients after liver transplantation for HCV. Author(s): Langrehr JM, Neumann UP, Lang M, Muller AR, Jonas S, Settmacher U, Steinmuller T, Neuhaus P. Source: Transplantation Proceedings. 2002 August; 34(5): 1565-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176487&dopt=Abstract
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Flow-mediated, endothelium-dependent vasodilatation is impaired in male body builders taking anabolic-androgenic steroids. Author(s): Ebenbichler CF, Sturm W, Ganzer H, Bodner J, Mangweth B, Ritsch A, Sandhofer A, Lechleitner M, Foger B, Patsch JR. Source: Atherosclerosis. 2001 October; 158(2): 483-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583730&dopt=Abstract
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Fluoride and anabolic steroids in the treatment of glucocorticoid-induced osteoporosis. Author(s): Marcocci C, Bevilacqua M. Source: Frontiers of Hormone Research. 2002; 30: 165-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892264&dopt=Abstract
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Fluoroscopic transforaminal lumbar epidural steroids: an outcome study. Author(s): Lutz GE, Vad VB, Wisneski RJ. Source: Archives of Physical Medicine and Rehabilitation. 1998 November; 79(11): 13626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9821894&dopt=Abstract
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Fluoroscopy is medically necessary for the performance of epidural steroids. Author(s): Manchikanti L, Bakhit CE, Pakanati RR, Fellows B. Source: Anesthesia and Analgesia. 1999 November; 89(5): 1330-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10553871&dopt=Abstract
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Focal segmental glomerulosclerosis in African Americans: effects of steroids and angiotensin converting enzyme inhibitors. Author(s): Crenshaw G, Bigler S, Salem M, Crook ED. Source: The American Journal of the Medical Sciences. 2000 May; 319(5): 320-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830556&dopt=Abstract
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Follicular fluid contents of hyaluronic acid, follicle-stimulating hormone and steroids relative to the success of in vitro fertilization of human oocytes. Author(s): Suchanek E, Simunic V, Juretic D, Grizelj V. Source: Fertility and Sterility. 1994 August; 62(2): 347-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8034084&dopt=Abstract
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Follicular fluid levels of insulin-like growth factor I, insulin-like growth factor binding protein I, and ovarian steroids collected during ovum pick-up. Author(s): Chang SY, Hsieh KC, Wang HS, Soong YK. Source: Fertility and Sterility. 1994 December; 62(6): 1162-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7525360&dopt=Abstract
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Follow up of growth and steroids in premature adrenarche. Author(s): Pere A, Perheentupa J, Peter M, Voutilainen R. Source: European Journal of Pediatrics. 1995 May; 154(5): 346-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641763&dopt=Abstract
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For and against. Should steroids be the first line treatment for asthma? Author(s): Strube G, Rudolf M. Source: Bmj (Clinical Research Ed.). 2000 January 1; 320(7226): 47-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617533&dopt=Abstract
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Formation and effects of neuroactive steroids in the central and peripheral nervous system. Author(s): Melcangi RC, Magnaghi V, Galbiati M, Martini L. Source: Int Rev Neurobiol. 2001; 46: 145-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599299&dopt=Abstract
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Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor. Author(s): Wetzel CH, Hermann B, Behl C, Pestel E, Rammes G, Zieglgansberger W, Holsboer F, Rupprecht R. Source: Molecular Endocrinology (Baltimore, Md.). 1998 September; 12(9): 1441-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731711&dopt=Abstract
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Further studies on the chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. Author(s): Pincus DJ, Humeston TR, Martin RJ. Source: The Journal of Allergy and Clinical Immunology. 1997 December; 100(6 Pt 1): 771-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9438485&dopt=Abstract
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GABA(A) receptor active steroids are altered in epilepsy patients with tuberous sclerosis. Author(s): di Michele F, Verdecchia M, Dorofeeva M, Costamagna L, Bernardi G, Curatolo P, Romeo E. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 667-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700317&dopt=Abstract
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Gas chromatographic and mass spectrometric analysis of conjugated steroids in urine. Author(s): Yoon JM, Lee KH. Source: Journal of Biosciences. 2001 December; 26(5): 627-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807292&dopt=Abstract
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Gas chromatographic-tandem mass spectrometric determination of anabolic steroids and their esters in hair. Application in doping control and meat quality control. Author(s): Gaillard Y, Vayssette F, Balland A, Pepin G. Source: J Chromatogr B Biomed Sci Appl. 1999 December 10; 735(2): 189-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10670734&dopt=Abstract
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GC-MS determination of steroids related to androgen biosynthesis in human hair with pentafluorophenyldimethylsilyl-trimethylsilyl derivatisation. Author(s): Choi MH, Chung BC. Source: The Analyst. 1999 September; 124(9): 1297-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736853&dopt=Abstract
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Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Author(s): Roemmich JN, Clark PA, Berr SS, Mai V, Mantzoros CS, Flier JS, Weltman A, Rogol AD. Source: The American Journal of Physiology. 1998 September; 275(3 Pt 1): E543-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725824&dopt=Abstract
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Genotyping of the type II 3beta-hydroxysteroid dehydrogenase gene (HSD3B2) in women with hirsutism and elevated ACTH-stimulated delta(5)-steroids. Author(s): Marui S, Russell AJ, Paula FJ, Dick-de-Paula I, Marcondes JA, Mendonca BB. Source: Fertility and Sterility. 2000 September; 74(3): 553-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973654&dopt=Abstract
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Glaucoma induced by steroids. Author(s): Chong NH. Source: Bmj (Clinical Research Ed.). 1994 July 30; 309(6950): 343. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8086894&dopt=Abstract
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Glial responses to steroids as markers of brain aging. Author(s): Nichols NR. Source: Journal of Neurobiology. 1999 September 15; 40(4): 585-601. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453058&dopt=Abstract
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Glial-neuronal interactions in the neuroendocrine control of mammalian puberty: facilitatory effects of gonadal steroids. Author(s): Ojeda SR, Ma YJ. Source: Journal of Neurobiology. 1999 September 15; 40(4): 528-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453054&dopt=Abstract
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GnRH and steroids in cancer. Author(s): Florio S, Pagnini U, Crispino A, Pacilio C, Crispino L, Giordano A. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 June 1; 7: D1590-608. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045004&dopt=Abstract
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Gonadal and adrenal sex steroids in ankylosing spondylitis. Author(s): Gooren LJ, Giltay EJ, van Schaardenburg D, Dijkmans BA. Source: Rheumatic Diseases Clinics of North America. 2000 November; 26(4): 969-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084954&dopt=Abstract
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Gonadal and adrenal steroids regulate neurochemical and structural plasticity of the hippocampus via cellular mechanisms involving NMDA receptors. Author(s): McEwen BS. Source: Cellular and Molecular Neurobiology. 1996 April; 16(2): 103-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8743963&dopt=Abstract
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Gonadal steroids and energy homeostasis in the leptin era. Author(s): Mystkowski P, Schwartz MW. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 October; 16(10): 937-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054599&dopt=Abstract
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Gonadal steroids and immunity. Author(s): Olsen NJ, Kovacs WJ. Source: Endocrine Reviews. 1996 August; 17(4): 369-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8854050&dopt=Abstract
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Gonadal steroids and neuronal function. Author(s): Alonso R, Lopez-Coviella I. Source: Neurochemical Research. 1998 May; 23(5): 675-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566606&dopt=Abstract
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Gonadal steroids in the treatment of mood disorders. Author(s): Epperson CN, Wisner KL, Yamamoto B. Source: Psychosomatic Medicine. 1999 September-October; 61(5): 676-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10511016&dopt=Abstract
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Gonadal steroids modulate interleukin-1 receptor antagonist mRNA expression in cultured human monocytes. Author(s): Lee BY, Huynh T, Prichard LE, McGuire J, Polan ML. Source: Biochemical and Biophysical Research Communications. 1995 April 6; 209(1): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726847&dopt=Abstract
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Gonadotrophin pulsatility in girls with the Turner syndrome: modulation by exogenous sex steroids. Author(s): Nathwani NC, Hindmarsh PC, Massarano AA, Brook CG. Source: Clinical Endocrinology. 1998 July; 49(1): 107-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9797854&dopt=Abstract
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Gonadotropin gene modulation by steroids and gonadotropin-releasing hormone. Author(s): Shupnik MA. Source: Biology of Reproduction. 1996 February; 54(2): 279-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8788177&dopt=Abstract
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Gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in human myometrium and leiomyomata and the direct action of GnRH analogs on myometrial smooth muscle cells and interaction with ovarian steroids in vitro. Author(s): Chegini N, Rong H, Dou Q, Kipersztok S, Williams RS. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 September; 81(9): 3215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8784072&dopt=Abstract
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Graft survival following living-donor renal transplantation: a comparison of tacrolimus and cyclosporine microemulsion with mycophenolate mofetil and steroids. Author(s): Bunnapradist S, Daswani A, Takemoto SK. Source: Transplantation. 2003 July 15; 76(1): 10-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865780&dopt=Abstract
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Granulomatous disease in common variable immunodeficiency: effect on immunoglobulin replacement therapy and response to steroids and splenectomy. Author(s): Spickett GP, Zhang JG, Green T, Shrimankar J. Source: Journal of Clinical Pathology. 1996 May; 49(5): 431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8707966&dopt=Abstract
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Growth effects of systemic versus inhaled steroids in chronic lung disease. Author(s): Nicholl RM, Greenough A, King M, Cheeseman P, Gamsu HR. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 July; 87(1): F59-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091295&dopt=Abstract
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Growth hormone and sex steroids. Interactions in puberty. Author(s): Mauras N. Source: Endocrinology and Metabolism Clinics of North America. 2001 September; 30(3): 529-44. Review. Erratum In: Endocrinol Metab Clin North Am 2001 December; 30(4): 319. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571929&dopt=Abstract
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Growth hormone in combination with anabolic steroids in patients with Turner syndrome: effect on bone maturation and final height. Author(s): Haeusler G, Schmitt K, Blumel P, Plochl E, Waldhor T, Frisch H. Source: Acta Paediatrica (Oslo, Norway : 1992). 1996 December; 85(12): 1408-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9001649&dopt=Abstract
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Growth hormone induced increase in serum IGFBP-3 level is reversed by anabolic steroids in substance abusing power athletes. Author(s): Karila T, Koistinen H, Seppala M, Koistinen R, Seppala T. Source: Clinical Endocrinology. 1998 October; 49(4): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9876343&dopt=Abstract
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Growth hormone, insulin-like growth factor-I and lipid metabolism: interactions with sex steroids. Author(s): Bjorntorp P. Source: Hormone Research. 1996; 46(4-5): 188-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8950619&dopt=Abstract
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Hair analysis of seven bodybuilders for anabolic steroids, ephedrine, and clenbuterol. Author(s): Dumestre-Toulet V, Cirimele V, Ludes B, Gromb S, Kintz P. Source: J Forensic Sci. 2002 January; 47(1): 211-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064656&dopt=Abstract
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Hazards of systemic steroids for ventilator-dependent preterm infants: what would a parent want? Author(s): Barrington KJ. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 July 10; 165(1): 33-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468952&dopt=Abstract
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Hepatic focal nodular hyperplasia in infant antenatally exposed to steroids. Author(s): Prasad VK, Aronson DC, Gerald WL, Meyers PA, La Quaglia MP. Source: Lancet. 1995 August 5; 346(8971): 371. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7623541&dopt=Abstract
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Hepatitis C-associated peripheral corneal ulceration: rapid response to intravenous steroids. Author(s): Pluznik D, Butrus SI. Source: Cornea. 2001 November; 20(8): 888-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685073&dopt=Abstract
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Herpes zoster: a previously unrecognized complication of epidural steroids in the treatment of complex regional pain syndrome. Author(s): Parsons SJ, Hawboldt GS. Source: Journal of Pain and Symptom Management. 2003 March; 25(3): 198-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614953&dopt=Abstract
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HHV-8-associated primary cerebral B-cell lymphoma in HIV-negative patient after long-term steroids. Author(s): Luppi M, Barozzi P, Marasca R, Savarino M, Torelli G. Source: Lancet. 1996 April 6; 347(9006): 980. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8598800&dopt=Abstract
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High-dose inhaled steroids in asthmatic children. Author(s): Brus RH, Bodenheimer S. Source: Lancet. 1996 September 21; 348(9030): 820-1; Author Reply 821. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8813997&dopt=Abstract
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High-dose inhaled steroids in asthmatic children. Author(s): Lipworth BJ, Clark D. Source: Lancet. 1996 September 21; 348(9030): 820; Author Reply 821. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8813996&dopt=Abstract
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High-dose inhaled steroids in asthmatic children. Author(s): Lenney W. Source: Lancet. 1996 September 21; 348(9030): 819-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8813995&dopt=Abstract
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High-dose inhaled steroids in asthmatic children. Author(s): Cade A, Butler GE, Morrison JF, Chetcuti PJ. Source: Lancet. 1996 September 21; 348(9030): 819. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8813994&dopt=Abstract
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High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society. Author(s): Boe J, Bakke P, Rodolen T, Skovlund E, Gulsvik A. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1994 December; 7(12): 2179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7713201&dopt=Abstract
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Higher dose inhaled steroids in childhood asthma. Conventional doses do have side effects. Author(s): Archer H, Creese K, Doull I. Source: Bmj (Clinical Research Ed.). 2001 June 23; 322(7301): 1546. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439998&dopt=Abstract
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Higher dose inhaled steroids in childhood asthma. Why isn't titration advocated more often in delivery of inhaled drugs? Author(s): Cates C. Source: Bmj (Clinical Research Ed.). 2001 June 23; 322(7301): 1546. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439999&dopt=Abstract
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High-performance liquid chromatographic optimization study for the separation of natural and synthetic anabolic steroids. Application to urine and pharmaceutical samples. Author(s): Gonzalo-Lumbreras R, Izquierdo-Hornillos R. Source: J Chromatogr B Biomed Sci Appl. 2000 May 26; 742(1): 1-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10892579&dopt=Abstract
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High-risk behaviors among high school students in Massachusetts who use anabolic steroids. Author(s): Middleman AB, Faulkner AH, Woods ER, Emans SJ, DuRant RH. Source: Pediatrics. 1995 August; 96(2 Pt 1): 268-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7630682&dopt=Abstract
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High-throughput sample preparation and analysis using 96-well membrane solidphase extraction and liquid chromatography-tandem mass spectrometry for the determination of steroids in human urine. Author(s): Rule G, Henion J. Source: Journal of the American Society for Mass Spectrometry. 1999 December; 10(12): 1322-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584329&dopt=Abstract
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Hirsutism and acne in women: coordinated radioimmunoassays for eight relevant plasma steroids. Author(s): Fiet J, Gosling JP, Soliman H, Galons H, Boudou P, Aubin P, Belanger A, Villette JM, Julien R, Brerault JL, et al. Source: Clinical Chemistry. 1994 December; 40(12): 2296-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7988017&dopt=Abstract
Studies 181
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Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes. Author(s): Elimian A, Verma U, Beneck D, Cipriano R, Visintainer P, Tejani N. Source: Obstetrics and Gynecology. 2000 September; 96(3): 333-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960621&dopt=Abstract
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HIV risk behaviours among gay men who use anabolic steroids. Author(s): Bolding G, Sherr L, Maguire M, Elford J. Source: Addiction (Abingdon, England). 1999 December; 94(12): 1829-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717961&dopt=Abstract
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Holding chambers versus nebulisers for inhaled steroids in chronic asthma. Author(s): Cates CJ, Adams N, Bestall J. Source: Cochrane Database Syst Rev. 2001; (2): Cd001491. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405994&dopt=Abstract
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Homing-in on the origin of biliary steroids. Author(s): Carey MC. Source: Gut. 1997 November; 41(5): 721-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9414991&dopt=Abstract
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Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome. Author(s): Vrbikova J, Bicikova M, Tallova J, Hill M, Starka L. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2002 April; 110(2): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928069&dopt=Abstract
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Hormonal treatment with sex steroids in women is associated with lower p105 serum concentrations. Author(s): Meden H, Mielke S, Marx D, Wuttke W, Kuhn W. Source: Anticancer Res. 1997 July-August; 17(4B): 3075-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329605&dopt=Abstract
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Hormones: androgens, antiandrogens, anabolic steroids, estrogens--unapproved uses or indications. Author(s): Gunes AT, Fetil E. Source: Clinics in Dermatology. 2000 January-February; 18(1): 55-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701086&dopt=Abstract
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How do steroids act? Author(s): Ramirez VD. Source: Lancet. 1996 March 9; 347(9002): 630-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8596371&dopt=Abstract
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How do steroids work? Author(s): Schleimer RP. Source: American Journal of Respiratory and Critical Care Medicine. 1996 June; 153(6 Pt 2): S28-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8646382&dopt=Abstract
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How effective are nasal steroids combined with nonsedating antihistamines for seasonal allergic rhinitis? Author(s): Andy C, Thering A. Source: The Journal of Family Practice. 2002 July; 51(7): 616. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160498&dopt=Abstract
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How effective are weekly antenatal steroids for decreasing the risks associated with preterm delivery? Author(s): Burgert W 3rd, Newton WP. Source: The Journal of Family Practice. 2002 January; 51(1): 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927053&dopt=Abstract
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How to do without steroids in inflammatory bowel disease. Author(s): Present DH. Source: Inflammatory Bowel Diseases. 2000 February; 6(1): 48-57; Discussion 58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701150&dopt=Abstract
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HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. Author(s): Taylor HS, Arici A, Olive D, Igarashi P. Source: The Journal of Clinical Investigation. 1998 April 1; 101(7): 1379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9525980&dopt=Abstract
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Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21steroids. Author(s): Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R. Source: Journal of Molecular Biology. 2003 August 15; 331(3): 593-604. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899831&dopt=Abstract
Studies 183
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Human androgenic steroids affect growth of dermatophytes in vitro. Author(s): Brasch J, Flader S. Source: Mycoses. 1996 September-October; 39(9-10): 387-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9009664&dopt=Abstract
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Hybrid gene or hybrid steroids in the detection and screening for familial hyperaldosteronism type I. Author(s): Stowasser M, Bachmann AW, Jonsson JR, Tunny TJ, Klemm SA, Gordon RD. Source: Clinical and Experimental Pharmacology & Physiology. 1995 June-July; 22(6-7): 444-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8582097&dopt=Abstract
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Hydrolysis of conjugated steroids by the combined use of beta-glucuronidase preparations from helix pomatia and ampullaria: determination of urinary cortisol and its metabolites. Author(s): Shibasaki H, Tanabe C, Furuta T, Kasuya Y. Source: Steroids. 2001 November; 66(11): 795-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576618&dopt=Abstract
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Hyperlipidemia in children: the role of uremia, steroids and cyclosporine therapy. Author(s): Singh A, Tejani A. Source: Nephron. 1996; 74(3): 529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938676&dopt=Abstract
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Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia. Author(s): Dessein PH, Shipton EA, Joffe BI, Hadebe DP, Stanwix AE, Van der Merwe BA. Source: Pain. 1999 November; 83(2): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534604&dopt=Abstract
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Immune up-regulation and tumor apoptosis by androstene steroids. Author(s): Loria RM. Source: Steroids. 2002 November; 67(12): 953-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398992&dopt=Abstract
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Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty. Author(s): Cursiefen C, Wenkel H, Martus P, Langenbucher A, Nguyen NX, Seitz B, Kuchle M, Naumann GO. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2001 July; 239(7): 514-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521696&dopt=Abstract
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Impact of steroids on recovery after uvulopalatopharyngoplasty. Author(s): Williams PM, Strome M, Eliachar I, Lavertu P, Wood BG, Vito KJ. Source: The Laryngoscope. 1999 December; 109(12): 1941-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10591351&dopt=Abstract
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Improved survival and neurodevelopmental outcome after prolonged ventilation in preterm neonates who have received antenatal steroids and surfactant. Author(s): Gaillard EA, Cooke RW, Shaw NJ. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2001 May; 84(3): F194-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320047&dopt=Abstract
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Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins. Author(s): Straussberg R, Schonfeld T, Weitz R, Karmazyn B, Harel L. Source: Pediatric Neurology. 2001 February; 24(2): 139-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275464&dopt=Abstract
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In children with asthma, do inhaled steroids reduce linear growth (height)? Author(s): Epling J. Source: The Journal of Family Practice. 2000 July; 49(7): 657-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10923581&dopt=Abstract
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In patients with asthma that is not well controlled with inhaled steroids, does salmeterol (Serevent) or montelukast (Singulair) offer better symptom relief? Author(s): Cash R, Blonski J. Source: The Journal of Family Practice. 2001 September; 50(9): 802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11674917&dopt=Abstract
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In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. Author(s): Loppow D, Schleiss MB, Kanniess F, Taube C, Jorres RA, Magnussen H. Source: Respiratory Medicine. 2001 February; 95(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217907&dopt=Abstract
Studies 185
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In steroid sensitive nephrotic syndrome (SSNS) in children, is there clear evidence that steroids given every second day are more beneficial in terms of reducing relapse rate and side effects compared with half the dose given every day? Author(s): Hodson EM, Craig JC. Source: Pediatric Nephrology (Berlin, Germany). 2001 December; 16(12): 1159-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793121&dopt=Abstract
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In vivo effects of sex steroids on lymphocyte responsiveness and immunoglobulin levels in humans. Author(s): Giltay EJ, Fonk JC, von Blomberg BM, Drexhage HA, Schalkwijk C, Gooren LJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 April; 85(4): 164857. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770211&dopt=Abstract
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Increased 5alpha-reductase and normal 11beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome. Author(s): Chin D, Shackleton C, Prasad VK, Kohn B, David R, Imperato-McGinley J, Cohen H, McMahon DJ, Oberfield SE. Source: J Pediatr Endocrinol Metab. 2000 March; 13(3): 253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714750&dopt=Abstract
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Increasing use of inhaled steroids associated with declining asthma mortality. Author(s): Kumana CR, Kou M, Lauder IJ, Ip MS, Lam WK. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 2001 April; 38(2): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11321687&dopt=Abstract
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Indications for and questions about antenatal steroids. Author(s): Jobe AH. Source: Adv Pediatr. 2002; 49: 227-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214773&dopt=Abstract
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Induction with basiliximab reduces acute rejection in pediatric liver transplant patients treated with tacrolimus and steroids. Author(s): Asensio M, Margarit C, Chavez R, Ortega J, Charco R, Iglesias J. Source: Transplantation Proceedings. 2002 August; 34(5): 1970-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176650&dopt=Abstract
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Industry and academy: the synthesis of steroids. Author(s): Slater LB. Source: Historical Studies in the Physical and Biological Sciences : Hsps / Office of History of Science and Technology, University of California, Berkeley. 2000; 30 Pt 2: 44380. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11624655&dopt=Abstract
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Infectious crystalline keratopathy following trabeculectomy and low-dose topical steroids. Author(s): Apel A, Campbell I, Rootman DS. Source: Cornea. 1995 May; 14(3): 321-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7600818&dopt=Abstract
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Influence of antenatal steroids and sex on maturation of the epidermal barrier in the preterm infant. Author(s): Jain A, Rutter N, Cartlidge PH. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2000 September; 83(2): F112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952704&dopt=Abstract
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Influence of gender and gonadal steroids on responsiveness to growth hormone replacement therapy in adults with growth hormone deficiency. Author(s): Johannsson G, Bengtsson BA. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 April; 8 Suppl B: 69-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10990137&dopt=Abstract
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Influence of inhaled steroids on pulmonary epithelial permeability to Tc99m-dTPA in atopic asthmatic children. Author(s): Yuksel H, Yuksel D, Demir E, Tanac R. Source: J Investig Allergol Clin Immunol. 2001; 11(3): 188-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831452&dopt=Abstract
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Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever. Author(s): Thio BJ, Slingerland GL, Fredriks AM, Nagelkerke AF, Scheeren RA, Neijens HJ, Roord JJ, Dankert-Roelse JE. Source: Thorax. 2000 October; 55(10): 826-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992533&dopt=Abstract
Studies 187
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Influence of sexual steroids on cell functions of PMNL in the gingival sulcus. Author(s): Klinger G, Glanzer S, Sigusch B, Klinger G, Romer W. Source: Pharmazie. 2000 September; 55(9): 678-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031772&dopt=Abstract
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Influence of sleep deprivation on neuroactive steroids in major depression. Author(s): Schule C, di Michele F, Baghai T, Romeo E, Bernardi G, Zwanzger P, Padberg F, Pasini A, Rupprecht R. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 March; 28(3): 577-81. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629540&dopt=Abstract
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Influence of steroids and methotrexate on wound complications after elective rheumatoid hand and wrist surgery. Author(s): Jain A, Witbreuk M, Ball C, Nanchahal J. Source: The Journal of Hand Surgery. 2002 May; 27(3): 449-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12015719&dopt=Abstract
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Influence of steroids on oxidant generation in activated human granulocytes and mononuclear leukocytes. Author(s): Cassidy RA. Source: Shock (Augusta, Ga.). 2003 July; 20(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813374&dopt=Abstract
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Inhalational and topical steroids, and oral candidosis: a mini review. Author(s): Ellepola AN, Samaranayake LP. Source: Oral Diseases. 2001 July; 7(4): 211-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575870&dopt=Abstract
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Inhaled steroids - too much of a good thing? Author(s): Wilson JW, Robertson CF. Source: The Medical Journal of Australia. 2002 September 16; 177(6): 288-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225273&dopt=Abstract
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Inhaled steroids and asthma. Author(s): Blaiss MS. Source: Pediatrics. 2002 November; 110(5): 1030-1; Author Reply 1030-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415050&dopt=Abstract
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Inhaled steroids and local side-effects. Author(s): Carlsen KH. Source: Allergy. 2001 October; 56(10): 925-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576069&dopt=Abstract
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Inhaled steroids and the risk of adrenal suppression in children. Author(s): Robinson JD, Angelini BL, Krahnke JS, Skoner DP. Source: Expert Opinion on Drug Safety. 2002 September; 1(3): 237-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904139&dopt=Abstract
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Inhaled steroids as prophylaxis for delayed pulmonary toxicity syndrome in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation. Author(s): McGaughey DS, Nikcevich DA, Long GD, Vredenburgh JJ, Rizzieri D, Smith CA, Broadwater G, Loftis JS, McDonald C, Morris AK, Folz RF, Chao NF. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2001; 7(5): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400949&dopt=Abstract
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Inhaled steroids for bronchiectasis. Author(s): Kolbe J, Wells A, Ram FS. Source: Cochrane Database Syst Rev. 2000; (2): Cd000996. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796575&dopt=Abstract
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Inhaled steroids for children's acute asthma exacerbations? Author(s): Garrett J. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 January; 88(1): 69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814283&dopt=Abstract
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Inhaled steroids for chronic obstructive pulmonary disease--where are we now? Author(s): Taylor DR, Wong CS. Source: N Z Med J. 2000 August 11; 113(1115): 337-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008612&dopt=Abstract
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Inhaled steroids for COPD? Author(s): Tattersfield AE, Harrison TW. Source: Thorax. 2001 September; 56 Suppl 2: Ii2-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514699&dopt=Abstract
Studies 189
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Inhaled steroids for episodic viral wheeze of childhood. Author(s): McKean M, Ducharme F. Source: Cochrane Database Syst Rev. 2000; (2): Cd001107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796596&dopt=Abstract
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Inhaled steroids for neonatal chronic lung disease. Author(s): Lister P, Iles R, Shaw B, Ducharme F. Source: Cochrane Database Syst Rev. 2000; (3): Cd002311. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908553&dopt=Abstract
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Inhaled steroids for sarcoidosis? Author(s): Kirsten D. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1995 May; 8(5): 679-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7656935&dopt=Abstract
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Inhaled steroids in acute asthma following emergency department discharge. Author(s): Edmonds ML, Camargo CA, Saunders LD, Brenner BE, Rowe BH. Source: Cochrane Database Syst Rev. 2000; (3): Cd002316. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908556&dopt=Abstract
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Inhaled steroids in asthma. Should the doses be reduced? Author(s): Bowler S. Source: Aust Fam Physician. 2002 August; 31(8): 746-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189668&dopt=Abstract
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Inhaled steroids in chronic obstructive pulmonary disease. Author(s): Anthonisen NR. Source: Can Respir J. 2002 January-February; 9(1): 11-2, 16-7. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856985&dopt=Abstract
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Inhaled steroids in the treatment of mild to moderate persistent asthma in children: once or twice daily administration? Author(s): Radzik D, Pavanello L. Source: Archives of Disease in Childhood. 2002 November; 87(5): 415-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390916&dopt=Abstract
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Inhaled steroids--too much of a good thing? Author(s): Goeman DP, Sawyer SM, Abramson MJ, Stewart K, Thien FC, Aroni RA, Douglass JA. Source: The Medical Journal of Australia. 2003 March 3; 178(5): 247. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603196&dopt=Abstract
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Inhaled vs oral steroids for adults with chronic asthma. Author(s): Mash B, Bheekie A, Jones PW. Source: Cochrane Database Syst Rev. 2001; (1): Cd002160. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279754&dopt=Abstract
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Inhaled vs oral steroids for adults with chronic asthma. Author(s): Cochrane Database Syst Rev. 2001;(4):CD000194 Source: Cochrane Database Syst Rev. 2000; (2): Cd002160. Review. Update In: /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11687072
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Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10. Author(s): Li YH, Brauner A, Jonsson B, Van der Ploeg I, Soder O, Holst M, Jensen JS, Lagercrantz H, Tullus K. Source: Biology of the Neonate. 2001 August; 80(2): 124-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509812&dopt=Abstract
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Initial clinical experience with interleukin-2 receptor antagonist induction in combination with tacrolimus, mycophenolate mofetil and steroids in simultaneous kidney-pancreas transplantation. Author(s): Lo A, Stratta RJ, Alloway RR, Egidi MF, Shokouh-Amiri MH, Grewal HP, Gaber LW, Gaber AO. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2001 December; 14(6): 396-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793037&dopt=Abstract
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Integration of the metabolic pathways of steroids, carotenoids, and retinoids. Author(s): Gawienowski AM. Source: Critical Reviews in Biochemistry and Molecular Biology. 1999; 34(6): 405-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711785&dopt=Abstract
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Interaction of intra-articular steroids and bupropion. Author(s): White P. Source: Clinical Radiology. 2002 March; 57(3): 235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952327&dopt=Abstract
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Interaction of steroids with the GABA(A) receptor. Author(s): Hamilton NM. Source: Current Topics in Medicinal Chemistry. 2002 August; 2(8): 887-902. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171578&dopt=Abstract
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Interferon versus steroids in patients with hepatitis C virus-associated cryoglobulinaemic glomerulonephritis. Author(s): Mazzaro C, Panarello G, Carniello S, Faelli A, Mazzi G, Crovatto M, Baracetti S, Nascimben F, Zorat F, Pozzato G, Faccini L, Campanacci L. Source: Dig Liver Dis. 2000 November; 32(8): 708-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142582&dopt=Abstract
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International congress on hormonal steroids and hormones in cancer. Author(s): Fuller PJ. Source: Expert Opinion on Investigational Drugs. 2003 February; 12(2): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556223&dopt=Abstract
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Interpreting risks of steroids for preterm infants. Author(s): Clark RH, Peabody JL. Source: The Journal of Pediatrics. 2000 October; 137(4): 590-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11035850&dopt=Abstract
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Intra-articular steroids after arthroscopy for osteoarthritis of the knee. Author(s): Peckett WR, Butler-Manuel A. Source: The Journal of Bone and Joint Surgery. British Volume. 2000 July; 82(5): 775-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10963186&dopt=Abstract
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Intra-articular steroids after arthroscopy for osteoarthritis of the knee. Author(s): Gosal HS, Jackson AM, Bickerstaff DR. Source: The Journal of Bone and Joint Surgery. British Volume. 1999 November; 81(6): 952-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10615964&dopt=Abstract
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Intralesional steroids augment the effects of endoscopic dilation in corrosive esophageal strictures. Author(s): Kochhar R, Ray JD, Sriram PV, Kumar S, Singh K. Source: Gastrointestinal Endoscopy. 1999 April; 49(4 Pt 1): 509-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202068&dopt=Abstract
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Intranasal steroids and the risk of emergency department visits for asthma. Author(s): Adams RJ, Fuhlbrigge AL, Finkelstein JA, Weiss ST. Source: The Journal of Allergy and Clinical Immunology. 2002 April; 109(4): 636-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11941313&dopt=Abstract
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Intranasal steroids or antihistamines for allergic rhinitis? Author(s): Grimm KJ. Source: The Journal of Family Practice. 1999 March; 48(3): 170-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086753&dopt=Abstract
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Intraocular pressure elevation in a child due to the use of inhalation steroids--a case report. Author(s): Desnoeck M, Casteels I, Casteels K. Source: Bull Soc Belge Ophtalmol. 2001; (280): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486469&dopt=Abstract
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Intraspinal steroids: history, efficacy, accidentality, and controversy with review of United States Food and Drug Administration reports. Author(s): Nelson DA, Landau WM. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 April; 70(4): 433-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254764&dopt=Abstract
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Intravenous anaesthesia: steroids. Author(s): Ball C, Westhorpe R. Source: Anaesthesia and Intensive Care. 2001 October; 29(5): 453. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669424&dopt=Abstract
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Intravitreal triamcinolone acetonide injection in blind painful eyes. Intraocular steroids as a treatment for blind painful red eyes. Author(s): Rodriguez ML, Juarez CP, Luna JD. Source: Eur J Ophthalmol. 2003 April; 13(3): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747651&dopt=Abstract
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Introduction to the special issue on neuroprotection by steroids: new perspectives. Author(s): Garcia-Segura LM, Wise PM. Source: Journal of Neurocytology. 2000 May-June; 29(5-6): 305-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11424947&dopt=Abstract
Studies 193
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Investigation into the rapid effects of 17 beta-estradiol and neuroactive steroids upon beta-amyloid(25-35)-induced activation of phosphoinositide-specific phospholipase C in human platelets. Author(s): Jonsson KO, Hedin HL, Fowler CJ. Source: Methods Find Exp Clin Pharmacol. 2000 October; 22(8): 615-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256232&dopt=Abstract
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Investigation of some commercially available spacer devices for the delivery of glucocorticoid steroids from a pMDI. Author(s): Williams RO 3rd, Patel AM, Barron MK, Rogers TL. Source: Drug Development and Industrial Pharmacy. 2001 May; 27(5): 401-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448047&dopt=Abstract
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Involvement of steroids and cytochromes P(450) species in the triggering of immune defenses. Author(s): Morfin R. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 March; 80(3): 273-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948012&dopt=Abstract
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Is complete avoidance of calcineurin inhibitors or steroids now possible? Importance of patient selection and choice of regimen. Author(s): Vincenti F. Source: Transplantation Proceedings. 2001 June; 33(4 Suppl): 11S-18S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406263&dopt=Abstract
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Is potent topical steroids the solution in collagenous colitis? Author(s): Lofberg R. Source: International Journal of Colorectal Disease. 1999 February; 14(1): 62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207733&dopt=Abstract
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Is there a role for androgenic anabolic steroids in medical practice? Author(s): Dobs AS. Source: Jama : the Journal of the American Medical Association. 1999 April 14; 281(14): 1326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10208149&dopt=Abstract
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Is there more to lung development than steroids and surfactant? Author(s): Rajagopal J, Kinane TB. Source: Pediatrics. 2000 November; 106(5): 1103-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061782&dopt=Abstract
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Isolation and structure elucidation of new cytotoxic steroids from the gorgonian Leptogorgia sarmentosa. Author(s): Garrido L, Zubia E, Ortega MJ, Salva J. Source: Steroids. 2000 February; 65(2): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639019&dopt=Abstract
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Keto/enol epoxy steroids as HIV-1 Tat inhibitors: structure-activity relationships and pharmacophore localization. Author(s): Michne WF, Schroeder JD, Bailey TR, Neumann HC, Cooke D, Young DC, Hughes JV, Kingsley SD, Ryan KA, Putz HS, et al. Source: Journal of Medicinal Chemistry. 1995 August 18; 38(17): 3197-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7650672&dopt=Abstract
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Kinase-mediated regulation of common transcription factors accounts for the boneprotective effects of sex steroids. Author(s): Kousteni S, Han L, Chen JR, Almeida M, Plotkin LI, Bellido T, Manolagas SC. Source: The Journal of Clinical Investigation. 2003 June; 111(11): 1651-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782668&dopt=Abstract
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Lack of effect of gender and oral contraceptive steroids on the pharmacokinetics of (R)-ibuprofen in humans. Author(s): Knights KM, McLean CF, Tonkin AL, Miners JO. Source: British Journal of Clinical Pharmacology. 1995 August; 40(2): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8562298&dopt=Abstract
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Large hepatic hematoma and intraabdominal hemorrhage associated with abuse of anabolic steroids. Author(s): Schumacher J, Muller G, Klotz KF. Source: The New England Journal of Medicine. 1999 April 8; 340(14): 1123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10206841&dopt=Abstract
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Left ventricular size and function in elite bodybuilders using anabolic steroids. Author(s): Dickerman RD, Schaller F, Zachariah NY, McConathy WJ. Source: Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine. 1997 April; 7(2): 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9113423&dopt=Abstract
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Legionella and Pneumocystis pneumonias in asthmatic children on high doses of systemic steroids. Author(s): Abernathy-Carver KJ, Fan LL, Boguniewicz M, Larsen GL, Leung DY. Source: Pediatric Pulmonology. 1994 September; 18(3): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7800428&dopt=Abstract
Studies 195
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Legionnella pulmonary infection in children on steroids. Author(s): Eber E, Varga EM, Zach MS. Source: Pediatric Pulmonology. 1995 June; 19(6): 398. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7567223&dopt=Abstract
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Leptin, reproduction and sex steroids. Author(s): Casabiell X, Pineiro V, Vega F, De La Cruz LF, Dieguez C, Casanueva FF. Source: Pituitary. 2001 January-April; 4(1-2): 93-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824514&dopt=Abstract
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Leukotriene receptor antagonists versus inhaled steroids in asthma. Author(s): Richardson CR. Source: The Journal of Family Practice. 1999 July; 48(7): 495-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10428241&dopt=Abstract
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Levels of plasma C19 steroids and 5 alpha-reduced C19 steroid glucuronides in primates, rodents, and domestic animals. Author(s): Guillemette C, Hum DW, Belanger A. Source: The American Journal of Physiology. 1996 August; 271(2 Pt 1): E348-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8770030&dopt=Abstract
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Life-threatening complications of hepatitis B virus-related polyarteritis nodosa developing despite interferon-alpha2b therapy: successful treatment with a combination of interferon, lamivudine, plasma exchanges and steroids. Author(s): Deleaval P, Stadler P, Descombes E, Hecker E, Schrago G, Chizzolini C, Nicole A, Pugin P, Regamey C. Source: Clinical Rheumatology. 2001; 20(4): 290-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529642&dopt=Abstract
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Limited benefits of induction with monoclonal antibody to interleukin-2 receptor in combination with tacrolimus, mycophenolate mofetil, and steroids in simultaneous kidney-pancreas transplantation. Author(s): Lo A, Stratta RJ, Alloway RR, Egidi MF, Shokouh-Amiri MH, Grewal HP, Gaber AO. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1701-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267477&dopt=Abstract
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Limiting myocardial cell injury during cardiopulmonary bypass: are steroids the answer? Author(s): Fenton KE, Dalton HJ. Source: Critical Care Medicine. 2003 June; 31(6): 1877-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794442&dopt=Abstract
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Lipid abnormalities in stable liver transplant recipients--effects of cyclosporin, tacrolimus, and steroids. Author(s): Fernandez-Miranda C, Guijarro C, de la Calle A, Loinaz C, Gonzalez-Pinto I, Gomez-Izquierdo T, Larumbe S, Moreno E, del Palacio A. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1998; 11(2): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9561680&dopt=Abstract
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Lipodystrophy despite anabolic steroids. Author(s): O'Mahony C, Price LM, Nelson M. Source: International Journal of Std & Aids. 1998 October; 9(10): 619. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9819116&dopt=Abstract
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Lipoprotein (a) and cholesterol in body builders using anabolic androgenic steroids. Author(s): Cohen LI, Hartford CG, Rogers GG. Source: Medicine and Science in Sports and Exercise. 1996 February; 28(2): 176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8775151&dopt=Abstract
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Local application of steroids following lumbar discectomy. Author(s): Debi R, Halperin N, Mirovsky Y. Source: Journal of Spinal Disorders & Techniques. 2002 August; 15(4): 273-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177541&dopt=Abstract
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Local biosynthesis of sex steroids in bone. Author(s): Compston J. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5398-400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466324&dopt=Abstract
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Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels. Author(s): Schubring C, Englaro P, Siebler T, Blum WF, Demirakca T, Kratzsch J, Kiess W. Source: Hormone Research. 1998; 50(5): 276-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9873196&dopt=Abstract
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Longitudinal study of adrenal steroids in a cohort of HIV-infected patients with hemophilia. Author(s): Chatterton RT Jr, Green D, Harris S, Grossman A, Hechter O. Source: The Journal of Laboratory and Clinical Medicine. 1996 June; 127(6): 545-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8648259&dopt=Abstract
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Long-term cardiovascular effects of anabolic steroids. Author(s): Madea B, Grellner W. Source: Lancet. 1998 July 4; 352(9121): 33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9800747&dopt=Abstract
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Long-term inhaled steroids. Although the general consensus seems to be that these agents are safe, what evidence exists about possible adverse effects from ongoing use of inhaled steroids. Author(s): Brent RL, McGeady SJ. Source: Pediatrics in Review / American Academy of Pediatrics. 2000 November; 21(11): 393-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077024&dopt=Abstract
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Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in relapsing-remitting MS. Author(s): Rio J, Nos C, Marzo ME, Tintore M, Montalban X. Source: Neurology. 1998 June; 50(6): 1910-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633761&dopt=Abstract
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Luteal phase ovarian steroids, stress arousal, premenses perceived stress, and premenstrual symptoms. Author(s): Woods NF, Lentz MJ, Mitchell ES, Shaver J, Heitkemper M. Source: Research in Nursing & Health. 1998 April; 21(2): 129-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535405&dopt=Abstract
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Lymphocyte subsets in cord blood of preterm infants: effect of antenatal steroids. Author(s): Chabra S, Cottrill C, Rayens MK, Cross R, Lipke D, Bruce M. Source: Biology of the Neonate. 1998; 74(3): 200-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9691160&dopt=Abstract
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Making the diagnosis of asthma. Trial of steroids is useful. Author(s): Crompton GK. Source: Bmj (Clinical Research Ed.). 1998 January 10; 316(7125): 150. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9462341&dopt=Abstract
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Management of chronic pain with epidural steroids. Author(s): Markey BT, Graham M. Source: Aorn Journal. 1997 April; 65(4): 791-2, 795-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9093742&dopt=Abstract
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Management of gynecomastia due to use of anabolic steroids in bodybuilders. Author(s): Babigian A, Silverman RT. Source: Plastic and Reconstructive Surgery. 2001 January; 107(1): 240-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176630&dopt=Abstract
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Management of infantile subglottic hemangioma: laser vaporization, submucous resection, intubation, or intralesional steroids? Author(s): Hoeve LJ, Kuppers GL, Verwoerd CD. Source: International Journal of Pediatric Otorhinolaryngology. 1997 December 10; 42(2): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9692627&dopt=Abstract
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Marked decrease of plasma neuroactive steroids during alcohol withdrawal. Author(s): Romeo E, Brancati A, De Lorenzo A, Fucci P, Furnari C, Pompili E, Sasso GF, Spalletta G, Troisi A, Pasini A. Source: Clinical Neuropharmacology. 1996 August; 19(4): 366-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8829001&dopt=Abstract
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Masseteric hypertrophy associated with administration of anabolic steroids and unilateral mastication: a case report. Author(s): Skoura C, Mourouzis C, Saranteas T, Chatzigianni E, Tesseromatis C. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 November; 92(5): 515-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709687&dopt=Abstract
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Massive steroids do not reduce the zone of injury after penetrating spinal cord injury. Author(s): Prendergast MR, Saxe JM, Ledgerwood AM, Lucas CE, Lucas WF. Source: The Journal of Trauma. 1994 October; 37(4): 576-9; Discussion 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7932887&dopt=Abstract
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Mechanism of action caudal steroids for piriformis syndrome. Author(s): Mullin V, de Rosayro M, Quint D. Source: Anesthesia and Analgesia. 1998 March; 86(3): 680. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9495448&dopt=Abstract
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Mechanisms of intranasal steroids in the management of upper respiratory allergic diseases. Author(s): Nelson HS. Source: The Journal of Allergy and Clinical Immunology. 1999 October; 104(4 Pt 1): S138-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10518810&dopt=Abstract
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Mediastinal lipomatosis and exogenous steroids. Author(s): Fauzi AR, Cheung HS. Source: Hosp Med. 2002 July; 63(7): 439. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187610&dopt=Abstract
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Mediating mechanisms in a program to reduce intentions to use anabolic steroids and improve exercise self-efficacy and dietary behavior. Author(s): MacKinnon DP, Goldberg L, Clarke GN, Elliot DL, Cheong J, Lapin A, Moe EL, Krull JL. Source: Prevention Science : the Official Journal of the Society for Prevention Research. 2001 March; 2(1): 15-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519372&dopt=Abstract
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Mediation of the cytotoxicity of lanostanoids and steroids of Ganoderma tsugae through apoptosis and cell cycle. Author(s): Gan KH, Fann YF, Hsu SH, Kuo KW, Lin CN. Source: Journal of Natural Products. 1998 April; 61(4): 485-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9584403&dopt=Abstract
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Medical complications of anabolic steroids. Author(s): Feller AA, Mylonakis E, Rich JD. Source: Medicine and Health, Rhode Island. 2002 November; 85(11): 338-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462865&dopt=Abstract
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Medical management of phimosis in children: our experience with topical steroids. Author(s): Monsour MA, Rabinovitch HH, Dean GE. Source: The Journal of Urology. 1999 September; 162(3 Pt 2): 1162-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458456&dopt=Abstract
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Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Author(s): Hart YM, Cortez M, Andermann F, Hwang P, Fish DR, Dulac O, Silver K, Fejerman N, Cross H, Sherwin A, et al. Source: Neurology. 1994 June; 44(6): 1030-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8208394&dopt=Abstract
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Megadose steroids in multiple sclerosis. Author(s): Bohr T. Source: Neurology. 1994 October; 44(10): 1988. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7936272&dopt=Abstract
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Melatonin and steroids in human pre-ovulatory follicular fluid: seasonal variations and granulosa cell steroid production. Author(s): Yie SM, Brown GM, Liu GY, Collins JA, Daya S, Hughes EG, Foster WG, Younglai EV. Source: Human Reproduction (Oxford, England). 1995 January; 10(1): 50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7745070&dopt=Abstract
•
Metabolic effects of infection and postnatal steroids. Author(s): Schwarzenberg SJ, Kovacs A. Source: Clin Perinatol. 2002 June; 29(2): 295-312. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168243&dopt=Abstract
•
Metabolic findings after liver transplantation within a randomised trial with or without steroids. Author(s): Tisone G, Angelico M, Vennarecci G, Palmieri G, Buonomo O, Negrini S, Casciani CU. Source: Transplantation Proceedings. 1998 June; 30(4): 1447-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9636587&dopt=Abstract
•
Metabolic interrelationships, cardiovascular disease, and sex steroids. Author(s): Fotherby K. Source: Contraception. 1998 March; 57(3): 183-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9617534&dopt=Abstract
•
Metabolism of anabolic androgenic steroids. Author(s): Schanzer W. Source: Clinical Chemistry. 1996 July; 42(7): 1001-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8674183&dopt=Abstract
•
Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites. Author(s): Rendic S, Nolteernsting E, Schanzer W. Source: J Chromatogr B Biomed Sci Appl. 1999 November 26; 735(1): 73-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10630892&dopt=Abstract
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Metabolism of anabolic steroids in humans: synthesis of 6 beta-hydroxy metabolites of 4-chloro-1,2-dehydro-17 alpha-methyltestosterone, fluoxymesterone, and metandienone. Author(s): Schanzer W, Horning S, Donike M. Source: Steroids. 1995 April; 60(4): 353-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8539789&dopt=Abstract
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•
Metabolism of progesterone by human lymphocytes: production of neuroactive steroids. Author(s): Leb CR, Hu FY, Murphy BE. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 December; 82(12): 4064-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9398714&dopt=Abstract
•
Metabolism of steroids in the brain: a new insight into the role of 5alpha-reductase and aromatase in brain differentiation and functions. Author(s): Negri-Cesi P, Poletti A, Celotti F. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1996 August; 58(56): 455-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8918971&dopt=Abstract
•
Methanol-induced optic neuropathy: treatment with intravenous high dose steroids. Author(s): Sodhi PK, Goyal JL, Mehta DK. Source: Int J Clin Pract. 2001 November; 55(9): 599-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770356&dopt=Abstract
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Micellar electrokinetic capillary chromatographic separation of steroids in urine by trioctylphosphine oxide and cationic surfactant. Author(s): Abubaker MA, Petersen JR, Bissell MG. Source: Journal of Chromatography. B, Biomedical Applications. 1995 December 1; 674(1): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8749249&dopt=Abstract
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Micromolar concentrations of steroids and of aldosterone antagonists inhibit the outwardly rectifying chloride channel with different kinetics. Author(s): Rabe A, Fromter E. Source: Pflugers Archiv : European Journal of Physiology. 2000 March; 439(5): 559-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764215&dopt=Abstract
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Midcycle levels of sex steroids are sufficient to recreate the follicle-stimulating hormone but not the luteinizing hormone midcycle surge: evidence for the contribution of other ovarian factors to the surge in normal women. Author(s): Taylor AE, Whitney H, Hall JE, Martin K, Crowley WF Jr. Source: The Journal of Clinical Endocrinology and Metabolism. 1995 May; 80(5): 1541-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7744998&dopt=Abstract
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Misuse of androgenic-anabolic steroids and human deltoid muscle fibers: differences between polydrug regimens and single drug administration. Author(s): Hartgens F, van Straaten H, Fideldij S, Rietjens G, Keizer HA, Kuipers H. Source: European Journal of Applied Physiology. 2002 January; 86(3): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990732&dopt=Abstract
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Modifiable barriers to adherence to inhaled steroids among adults with asthma: it's not just black and white. Author(s): Apter AJ, Boston RC, George M, Norfleet AL, Tenhave T, Coyne JC, Birck K, Reisine ST, Cucchiara AJ, Feldman HI. Source: The Journal of Allergy and Clinical Immunology. 2003 June; 111(6): 1219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789220&dopt=Abstract
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Modulation of cognition-specific cortical activity by gonadal steroids: a positronemission tomography study in women. Author(s): Berman KF, Schmidt PJ, Rubinow DR, Danaceau MA, Van Horn JD, Esposito G, Ostrem JL, Weinberger DR. Source: Proceedings of the National Academy of Sciences of the United States of America. 1997 August 5; 94(16): 8836-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238064&dopt=Abstract
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Modulation of GABA(A) receptor function by neuroactive steroids: evidence for heterogeneity of steroid sensitivity of recombinant GABA(A) receptor isoforms. Author(s): Maitra R, Reynolds JN. Source: Canadian Journal of Physiology and Pharmacology. 1998 September; 76(9): 90920. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10066142&dopt=Abstract
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Modulation of GABAA receptor binding in human brain by neuroactive steroids: species and brain regional differences. Author(s): Nguyen Q, Sapp DW, Van Ness PC, Olsen RW. Source: Synapse (New York, N.Y.). 1995 February; 19(2): 77-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7725245&dopt=Abstract
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Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and human brain endothelial cells. Author(s): Dufour A, Corsini E, Gelati M, Ciusani E, Zaffaroni M, Giombini S, Massa G, Salmaggi A. Source: Journal of the Neurological Sciences. 1998 May 7; 157(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9619632&dopt=Abstract
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Modulation of immune responses by anabolic androgenic steroids. Author(s): Hughes TK, Fulep E, Juelich T, Smith EM, Stanton GJ. Source: International Journal of Immunopharmacology. 1995 November; 17(11): 857-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8788115&dopt=Abstract
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Modulation of middle ear epithelial function by steroids: clinical relevance. Author(s): Tan CT, Escoubet B, Van den Abbeele T, Friedlander G, Tran Ba Huy P, Herman P. Source: Acta Oto-Laryngologica. 1997 March; 117(2): 284-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9105467&dopt=Abstract
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Modulation of native and recombinant GABA(A) receptors by endogenous and synthetic neuroactive steroids. Author(s): Lambert JJ, Belelli D, Harney SC, Peters JA, Frenguelli BG. Source: Brain Research. Brain Research Reviews. 2001 November; 37(1-3): 68-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744075&dopt=Abstract
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Modulation of P-glycoprotein activity in Calu-3 cells using steroids and beta-ligands. Author(s): Hamilton KO, Yazdanian MA, Audus KL. Source: International Journal of Pharmaceutics. 2001 October 9; 228(1-2): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576779&dopt=Abstract
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Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma. Author(s): Matsuo H, Kurachi O, Shimomura Y, Samoto T, Maruo T. Source: Oncology. 1999 October; 57 Suppl 2: 49-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10545803&dopt=Abstract
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Molecular endocrinology. Steroids tickle cells inside and out. Author(s): Picard D. Source: Nature. 1998 April 2; 392(6675): 437-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9548245&dopt=Abstract
•
More on steroids after strabismus surgery. Author(s): Tripathi A, Marsh IB. Source: Journal of Pediatric Ophthalmology and Strabismus. 2000 November-December; 37(6): 326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392404&dopt=Abstract
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More reasons to hold on additional doses of antenatal steroids. Author(s): Nogee LM. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 March; 22(2): 99-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896512&dopt=Abstract
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MS-WHIM, new 3D theoretical descriptors derived from molecular surface properties: a comparative 3D QSAR study in a series of steroids. Author(s): Bravi G, Gancia E, Mascagni P, Pegna M, Todeschini R, Zaliani A. Source: Journal of Computer-Aided Molecular Design. 1997 January; 11(1): 79-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9139115&dopt=Abstract
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Multiple courses of antenatal steroids: risks and benefits. Author(s): Walfisch A, Hallak M, Mazor M. Source: Obstetrics and Gynecology. 2001 September; 98(3): 491-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530136&dopt=Abstract
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Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis. Author(s): Nakao A, Sakagami K, Nakata Y, Komazawa K, Amimoto T, Nakashima K, Isozaki H, Takakura N, Tanaka N. Source: Journal of Gastroenterology. 2000; 35(7): 557-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905366&dopt=Abstract
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Muscle inexcitability in patients with reversible paralysis following steroids and neuromuscular blockade. Author(s): Rich MM, Teener JW, Raps EC, Bird SJ. Source: Muscle & Nerve. 1998 September; 21(9): 1231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703456&dopt=Abstract
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Muscle weakness after short course of steroids. Author(s): Shee CD. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 February; 21(2): 377-8; Author Reply 378. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608456&dopt=Abstract
•
My engagement with steroids: a review. Author(s): Biglieri EG. Source: Steroids. 1995 January; 60(1): 52-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7792816&dopt=Abstract
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Mycophenolate mofetil, cyclosporine, and steroids after renal transplantation: fiveyear results at a single center. Author(s): Herrero JC, Morales E, Dominguez-Gil B, Carreno A, Cubas A, Andres A, Praga M, Ortuno T, Hernandez E, Rodicio JL, Morales JM. Source: Transplantation Proceedings. 1999 September; 31(6): 2263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500569&dopt=Abstract
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Myocardial infarction with extensive intracoronary thrombus induced by anabolic steroids. Author(s): Fisher M, Appleby M, Rittoo D, Cotter L. Source: Br J Clin Pract. 1996 June; 50(4): 222-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8759570&dopt=Abstract
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Nanjiols A-C, new steroids from the Chinese soft coral Nephthea bayeri. Author(s): Shao ZY, Zhu DY, Guo YW. Source: Journal of Natural Products. 2002 November; 65(11): 1675-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444699&dopt=Abstract
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Nasal steroids as treatment for obstructive sleep apnea: Don't throw away the scalpel yet. Author(s): Marcus CL. Source: The Journal of Pediatrics. 2001 June; 138(6): 795-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391318&dopt=Abstract
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Natural sex steroids and their xenobiotic analogs in animal production: growth, carcass quality, pharmacokinetics, metabolism, mode of action, residues, methods, and epidemiology. Author(s): Lone KP. Source: Critical Reviews in Food Science and Nutrition. 1997 March; 37(2): 93-209. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9101126&dopt=Abstract
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Natural steroids counteracting some actions of putative depressogenic steroids on the central nervous system: potential therapeutic benefits. Author(s): Dubrovsky B. Source: Medical Hypotheses. 1997 July; 49(1): 51-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9247908&dopt=Abstract
•
Necrotizing myocardial vasculitis in Churg-Strauss syndrome: clinicohistologic evaluation of steroids and immunosuppressive therapy. Author(s): Frustaci A, Gentiloni N, Chimenti C, Natale L, Gasbarrini G, Maseri A. Source: Chest. 1998 November; 114(5): 1484-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9824037&dopt=Abstract
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Need for precise diagnosis prior to epidural steroids. Author(s): Aldrete JA, Ghaly RF. Source: Anesthesiology. 2000 August; 93(2): 565-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910509&dopt=Abstract
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Negative feedback effects of gonadal steroids are preserved with aging in postmenopausal women. Author(s): Gill S, Lavoie HB, Bo-Abbas Y, Hall JE. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2297302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994380&dopt=Abstract
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Neonatal cord blood leptin: its relationship to birth weight, body mass index, maternal diabetes, and steroids. Author(s): Shekhawat PS, Garland JS, Shivpuri C, Mick GJ, Sasidharan P, Pelz CJ, McCormick KL. Source: Pediatric Research. 1998 March; 43(3): 338-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9505271&dopt=Abstract
•
Neonatal urinary steroids in Smith-Lemli-Opitz syndrome associated with 7dehydrocholesterol reductase deficiency. Author(s): Shackleton CH, Roitman E, Kelley R. Source: Steroids. 1999 July; 64(7): 481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10443904&dopt=Abstract
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Neuroactive steroids and anxiety disorders. Author(s): Le Melledo JM, Baker GB. Source: Journal of Psychiatry & Neuroscience : Jpn. 2002 May; 27(3): 161-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066445&dopt=Abstract
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Neuroactive steroids and central nervous system disorders. Author(s): Wang M, Backstrom T, Sundstrom I, Wahlstrom G, Olsson T, Zhu D, Johansson IM, Bjorn I, Bixo M. Source: Int Rev Neurobiol. 2001; 46: 421-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599309&dopt=Abstract
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Neuroactive steroids and seizure susceptibility. Author(s): Beyenburg S, Stoffel-Wagner B, Bauer J, Watzka M, Blumcke I, Bidlingmaier F, Elger CE. Source: Epilepsy Research. 2001 May; 44(2-3): 141-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325570&dopt=Abstract
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Neuroactive steroids in neuropsychopharmacology. Author(s): Rupprecht R, Holsboer F. Source: Int Rev Neurobiol. 2001; 46: 461-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599310&dopt=Abstract
•
Neuroactive steroids, relaxation, and seizure control. Author(s): Wiener P. Source: The International Journal of Neuroscience. 2003 May; 113(5): 631-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745624&dopt=Abstract
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Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal and umbilical blood: 3.3beta-hydroxy-5-ene steroids. Author(s): Hill M, Parizek A, Klak J, Hampl R, Sulcova J, Havlikova H, Lapcik O, Bicikova M, Fait T, Kancheva R, Cibula D, Pouzar V, Meloun M, Starka L. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 October; 82(23): 241-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477491&dopt=Abstract
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Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers. Author(s): Hill M, Bicikova M, Parizek A, Havlikova H, Klak J, Fajt T, Meloun M, Cibula D, Cegan A, Sulcova J, Hampl R, Starka L. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 July; 78(1): 517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530284&dopt=Abstract
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Neuroactive steroids, their precursors, and polar conjugates during parturition and postpartum in maternal and umbilical blood: 1. Identification and simultaneous determination of pregnanolone isomers. Author(s): Hill M, Parizek A, Bicikova M, Havlikova H, Klak J, Fait T, Cibula D, Hampl R, Cegan A, Sulcova J, Starka L. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2000 December 31; 75(4-5): 237-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282277&dopt=Abstract
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Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Author(s): Rupprecht R, Holsboer F. Source: Trends in Neurosciences. 1999 September; 22(9): 410-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441302&dopt=Abstract
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Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties. Author(s): Rupprecht R. Source: Psychoneuroendocrinology. 2003 February; 28(2): 139-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510009&dopt=Abstract
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Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology. Author(s): Rupprecht R, di Michele F, Hermann B, Strohle A, Lancel M, Romeo E, Holsboer F. Source: Brain Research. Brain Research Reviews. 2001 November; 37(1-3): 59-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744074&dopt=Abstract
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Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders. Author(s): Gasior M, Carter RB, Witkin JM. Source: Trends in Pharmacological Sciences. 1999 March; 20(3): 107-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203866&dopt=Abstract
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Neuroactive steroids: their mechanism of action and their function in the stress response. Author(s): Zinder O, Dar DE. Source: Acta Physiologica Scandinavica. 1999 November; 167(3): 181-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606819&dopt=Abstract
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Neurocognitive functioning in subjects with eating disorders: the influence of neuroactive steroids. Author(s): Galderisi S, Mucci A, Monteleone P, Sorrentino D, Piegari G, Maj M. Source: Biological Psychiatry. 2003 May 15; 53(10): 921-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742680&dopt=Abstract
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Neuroendocrine mechanisms underlying the control of gonadotropin secretion by steroids. Author(s): Mahesh VB, Brann DW. Source: Steroids. 1998 May-June; 63(5-6): 252-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618780&dopt=Abstract
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Neuropharmacology. Premenstrual steroids? Author(s): Britton KT, Koob GF. Source: Nature. 1998 April 30; 392(6679): 869-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9582066&dopt=Abstract
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Neuroregulatory role of gonadal steroids in humans. Author(s): Schmidt PJ, Rubinow DR. Source: Psychopharmacology Bulletin. 1997; 33(2): 219-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9230633&dopt=Abstract
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New 11 beta-aryl-substituted steroids exhibit both progestational and antiprogestational activity. Author(s): Rao PN, Wang Z, Cessac JW, Rosenberg RS, Jenkins DJ, Diamandis EP. Source: Steroids. 1998 October; 63(10): 523-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9800283&dopt=Abstract
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New advances in the understanding of the role of steroids and steroid receptors in disease. Author(s): Wiseman H, Duffy R. Source: Biochemical Society Transactions. 2001 May; 29(Pt 2): 205-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356155&dopt=Abstract
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New bioactive marine steroids from the Okinawan soft coral Clavularia viridis. Author(s): Watanabe K, Iwashima M, Iguchi K. Source: Steroids. 1996 July; 61(7): 439-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8837298&dopt=Abstract
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New spirostanol steroids and steroidal saponins from roots and rhizomes of Dracaena angustifolia and their antiproliferative activity. Author(s): Tran QL, Tezuka Y, Banskota AH, Tran QK, Saiki I, Kadota S. Source: Journal of Natural Products. 2001 September; 64(9): 1127-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575942&dopt=Abstract
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New steroids and new salicylates in inflammatory bowel disease: a critical appraisal. Author(s): Campieri M. Source: Gut. 2002 May; 50 Suppl 3: Iii43-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953332&dopt=Abstract
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New steroids for IBD: progress report. Author(s): Hanauer SB. Source: Gut. 2002 August; 51(2): 182-3. Erratum In: Gut 2002 October; 51(4): 616. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117876&dopt=Abstract
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New steroids from Clerodendrum colebrookianum. Author(s): Yang H, Wang J, Hou AJ, Guo YP, Lin ZW, Sun HD. Source: Fitoterapia. 2000 December; 71(6): 641-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077170&dopt=Abstract
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New steroids from Solenostemma argel leaves. Author(s): Hamed AI. Source: Fitoterapia. 2001 November; 72(7): 747-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11677012&dopt=Abstract
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No effect of high-dose inhaled steroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Author(s): Milman N, Graudal N, Grode G, Munch E. Source: Journal of Internal Medicine. 1994 September; 236(3): 285-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8077885&dopt=Abstract
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No influence of proinsulin and insulin on plasma levels of plasminogen activator inhibitor type 1 and tissue plasminogen activator in young women before and during intake of contraceptive steroids. Author(s): Petersen KR, Kjems LL, Skouby SO, Andersen LF, Jespersen J. Source: Metabolism: Clinical and Experimental. 1996 July; 45(7): 833-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8692017&dopt=Abstract
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No objective benefit from steroids inhaled via a spacer in infants recovering from bronchiolitis. Author(s): Wong JY, Moon S, Beardsmore C, O'Callaghan C, Simpson H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 February; 15(2): 388-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706509&dopt=Abstract
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No steroids or STITCH for CPB? Author(s): Kan H, Finkel MS. Source: Critical Care Medicine. 1999 March; 27(3): 463-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10199515&dopt=Abstract
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Nongenomic action of steroids in myometrial contractility. Author(s): Perusquia M. Source: Endocrine. 2001 June; 15(1): 63-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572328&dopt=Abstract
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Nongenomic actions of steroids on gonadotropin release. Author(s): Wiebe JP. Source: Recent Progress in Hormone Research. 1997; 52: 71-99; Discussion 99-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238848&dopt=Abstract
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Nongenomic actions of steroids--from the laboratory to clinical implications. Author(s): Gerdes D, Christ M, Haseroth K, Notzon A, Falkenstein E, Wehling M. Source: J Pediatr Endocrinol Metab. 2000 July-August; 13(7): 853-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968474&dopt=Abstract
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Nongenomic effects of steroids on the nicotinic acetylcholine receptor. Author(s): Barrantes FJ, Antollini SS, Bouzat CB, Garbus I, Massol RH. Source: Kidney International. 2000 April; 57(4): 1382-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10760071&dopt=Abstract
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Nonlinear binding of sex steroids to albumin and sex hormone binding globulin. Author(s): Zeginiadou T, Kolias S, Kouretas D, Antonoglou O. Source: Eur J Drug Metab Pharmacokinet. 1997 July-September; 22(3): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9358204&dopt=Abstract
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Non-nephrotic children with membranoproliferative glomerulonephritis: are steroids indicated? Author(s): Somers M, Kertesz S, Rosen S, Herrin J, Colvin R, Palacios de Carreta N, Kim M. Source: Pediatric Nephrology (Berlin, Germany). 1995 April; 9(2): 140-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794705&dopt=Abstract
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Nonsteroidal anti-inflammatories (NSAIDS), oral hypoglycemics, and topical steroids. An overview. Author(s): Guadara J, Guadara D. Source: Clin Podiatr Med Surg. 1998 October; 15(4): 687-703, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9917986&dopt=Abstract
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Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17 alphahydroxylase-C17,20-lyase (P450(17) alpha): potential agents for the treatment of prostate cancer. Author(s): Njar VC, Kato K, Nnane IP, Grigoryev DN, Long BJ, Brodie AM. Source: Journal of Medicinal Chemistry. 1998 March 12; 41(6): 902-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9526564&dopt=Abstract
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Novel cytokine release inhibitors. Part II: Steroids. Author(s): He W, Huang FC, Morytko M, Jariwala N, Yu KT. Source: Bioorganic & Medicinal Chemistry Letters. 1998 October 20; 8(20): 2825-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9873630&dopt=Abstract
212 Steroids
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Nuclear factor-kappa-B/steroid hormone receptor interactions as a functional basis of anti-inflammatory action of steroids in reproductive organs. Author(s): van der Burg B, van der Saag PT. Source: Molecular Human Reproduction. 1996 June; 2(6): 433-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238713&dopt=Abstract
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Nutritional status in active juvenile chronic arthritis not treated with steroids. Author(s): Strano CG, Polito C, Alessio M, Servodio Iammarrone C, Di Toro A, Todisco N, Marotta A. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 September; 84(9): 1010-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8652951&dopt=Abstract
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Obesity, insulin, sex steroids and ovulation. Author(s): Nestler JE. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2000 June; 24 Suppl 2: S71-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997613&dopt=Abstract
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Observational evidence for the efficacy of antenatal steroids from randomized studies of surfactant replacement. Author(s): Gunkel JH, Mitchell BR. Source: American Journal of Obstetrics and Gynecology. 1995 July; 173(1): 281-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7631704&dopt=Abstract
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Occlusion of potent topical steroids. Author(s): Yen A, Raimer SS. Source: Archives of Dermatology. 1995 February; 131(2): 227. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7857127&dopt=Abstract
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Occlusion of potent topical steroids. Author(s): Menter A. Source: Archives of Dermatology. 1995 February; 131(2): 226-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7857126&dopt=Abstract
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Occurrence and risk factors of oral candidiasis treated with oral antifungals in seniors using inhaled steroids. Author(s): Kennedy WA, Laurier C, Gautrin D, Ghezzo H, Pare M, Malo JL, Contandriopoulos AP. Source: Journal of Clinical Epidemiology. 2000 July; 53(7): 696-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10941946&dopt=Abstract
Studies 213
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Ocular leprosy: do steroids complicate matters? Author(s): Daniel E, Alexander R, Chacko S. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 1995 March; 63(1): 115-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7730712&dopt=Abstract
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Ocular-hypertensive response to topical steroids in children. Author(s): Kwok AK, Lam DS, Ng JS, Fan DS, Chew SJ, Tso MO. Source: Ophthalmology. 1997 December; 104(12): 2112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9400772&dopt=Abstract
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Oestrogenic steroids and melanoma cell interaction with adjacent skin cells influence invasion of melanoma cells in vitro. Author(s): Neil SM, Eves P, Richardson B, Molife R, Lorigan P, Wagner M, Layton C, Morandini R, Ghanem G. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2000; 13 Suppl 8: 68-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11041360&dopt=Abstract
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On call. I know that men have more heart disease than women and that athletes who use steroids can have heart attacks. Are male hormones responsible for heart disease in ordinary men like me? Author(s): Simon HB. Source: Harvard Men's Health Watch. 2001 January; 5(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11137969&dopt=Abstract
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On the mechanism of interaction of steroids with human glucose 6-phosphate dehydrogenase. Author(s): Gordon G, Mackow MC, Levy HR. Source: Archives of Biochemistry and Biophysics. 1995 April 1; 318(1): 25-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726568&dopt=Abstract
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One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density. Author(s): Hughes JA, Conry BG, Male SM, Eastell R. Source: Thorax. 1999 March; 54(3): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10325897&dopt=Abstract
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Opposition to treatment of traumatic hyphema with antifibrinolytics/steroids. Author(s): Romano PE, Smith RJ. Source: Binocul Vis Strabismus Q. 2000 Summer; 15(2): 163-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893458&dopt=Abstract
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Optimization of the high-performance liquid chromatographic separation of a complex mixture containing urinary steroids, boldenone and bolasterone: application to urine samples. Author(s): Gonzalo-Lumbreras R, Izquierdo-Hornillos R. Source: J Chromatogr B Biomed Sci Appl. 2000 May 26; 742(1): 47-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10892583&dopt=Abstract
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Oral and inhaled steroids in croup: a randomized, placebo-controlled trial. Author(s): Geelhoed GC, Macdonald WB. Source: Pediatric Pulmonology. 1995 December; 20(6): 355-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8649914&dopt=Abstract
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Oral and intravenous steroids in giant cell arteritis. Author(s): Chan CC, O'Day J. Source: Clinical & Experimental Ophthalmology. 2003 June; 31(3): 179-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786766&dopt=Abstract
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Oral cyclosporine in patients with active severe ulcerative colitis not responding to steroids. Author(s): Sood A, Midha V, Sood N. Source: Indian J Gastroenterol. 2002 July-August; 21(4): 155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385545&dopt=Abstract
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Oral hairy leukoplakia in a HIV-negative asthmatic patient on systemic steroids. Author(s): Zakrzewska JM, Aly Z, Speight PM. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1995 July; 24(6): 282-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7562666&dopt=Abstract
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Oral microemulsion cyclosporin to reduce steroids rapidly in chronic active ulcerative colitis. Author(s): Actis GC, Volpes R, Rizzetto M. Source: European Journal of Gastroenterology & Hepatology. 1999 August; 11(8): 905-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10514126&dopt=Abstract
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Oral or intravenous steroids in acute severe asthma. Author(s): Smith M. Source: Journal of Accident & Emergency Medicine. 1999 July; 16(4): 281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417938&dopt=Abstract
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Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children. Author(s): Butler CC, Van Der Voort JH. Source: Cochrane Database Syst Rev. 2002; (4): Cd001935. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519563&dopt=Abstract
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Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children. Author(s): Butler CC, van Der Voort JH. Source: Cochrane Database Syst Rev. 2000; (4): Cd001935. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034736&dopt=Abstract
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Oral steroids and inflammatory markers in asthma. Author(s): Bush A, Hogg C, Corrigan CJ. Source: Archives of Disease in Childhood. 2001 May; 84(5): 452-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368039&dopt=Abstract
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Oral steroids and inflammatory markers in asthma. Author(s): Griff J. Source: Archives of Disease in Childhood. 2001 February; 84(2): 187. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232557&dopt=Abstract
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Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. Author(s): van Gestel AM, Laan RF, Haagsma CJ, van de Putte LB, van Riel PL. Source: British Journal of Rheumatology. 1995 April; 34(4): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7788149&dopt=Abstract
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Oral steroids for bronchiectasis (stable and acute exacerbations). Author(s): Lasserson T, Holt K, Greenstone M. Source: Cochrane Database Syst Rev. 2001; (4): Cd002162. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687146&dopt=Abstract
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Oral steroids for cystic fibrosis. Author(s): Cheng K, Ashby D, Smyth R. Source: Cochrane Database Syst Rev. 2000; (2): Cd000407. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796717&dopt=Abstract
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Oral steroids in the treatment of otitis externa. Author(s): Golder J. Source: Aust Fam Physician. 1999 August; 28(8): 775. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10495523&dopt=Abstract
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Oral versus i.v. steroids for children hospitalized with asthma. Author(s): Agrawal M, French L. Source: The Journal of Family Practice. 1999 August; 48(8): 578-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496630&dopt=Abstract
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Oral versus IV steroids for asthma. Author(s): Blazys D. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 2001 February; 27(1): 45-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759623&dopt=Abstract
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Oral vs i.v. steroids for asthma. Author(s): Margo K, Shaughnessy AF. Source: The Journal of Family Practice. 1997 May; 44(5): 441. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9152255&dopt=Abstract
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Osteoporosis in juvenile systemic lupus erythematosus: a longitudinal study on the effect of steroids on bone mineral density. Author(s): Trapani S, Civinini R, Ermini M, Paci E, Falcini F. Source: Rheumatology International. 1998; 18(2): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9782532&dopt=Abstract
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Outcome of cough variant asthma treated with inhaled steroids. Author(s): Cheriyan S, Greenberger PA, Patterson R. Source: Ann Allergy. 1994 December; 73(6): 478-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7998659&dopt=Abstract
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Outcomes in the Guillain Barre syndrome: the role of steroids. Author(s): Peter JV, Gnanamuthu C, Cherian AM, Prabhakar S. Source: J Assoc Physicians India. 1996 March; 44(3): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9251311&dopt=Abstract
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Ovarian steroids and serotonin neural function. Author(s): Bethea CL, Pecins-Thompson M, Schutzer WE, Gundlah C, Lu ZN. Source: Molecular Neurobiology. 1998 October; 18(2): 87-123. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10065876&dopt=Abstract
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Ovarian steroids and the brain: implications for cognition and aging. Author(s): McEwen BS, Alves SE, Bulloch K, Weiland NG. Source: Neurology. 1997 May; 48(5 Suppl 7): S8-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9153161&dopt=Abstract
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Ovarian steroids differentially modulate the gene expression of gonadotropinreleasing hormone neuronal subtypes in the ovariectomized cynomolgus monkey. Author(s): Krajewski SJ, Abel TW, Voytko ML, Rance NE. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 655-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574196&dopt=Abstract
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Ovarian steroids in endometrial angiogenesis. Author(s): Perrot-Applanat M, Ancelin M, Buteau-Lozano H, Meduri G, Bausero P. Source: Steroids. 2000 October-November; 65(10-11): 599-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108865&dopt=Abstract
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Ovarian steroids regulate the expression of basic fibroblast growth factor and its mRNA in fibroblasts derived from uterine endometrium. Author(s): Fujimoto J, Hori M, Ichigo S, Tamaya T. Source: Annals of Clinical Biochemistry. 1997 January; 34 ( Pt 1): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9022894&dopt=Abstract
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Over-the-counter anabolic steroids 4-androsten-3,17-dione; 4-androsten-3beta,17betadiol; and 19-nor-4-androsten-3,17-dione: excretion studies in men. Author(s): Uralets VP, Gillette PA. Source: Journal of Analytical Toxicology. 1999 September; 23(5): 357-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10488924&dopt=Abstract
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Over-the-counter delta5 anabolic steroids 5-androsen-3,17-dione; 5-androsten-3beta, 17beta-diol; dehydroepiandrosterone; and 19-nor-5-androsten-3,17-dione: excretion studies in men. Author(s): Uralets VP, Gillette PA. Source: Journal of Analytical Toxicology. 2000 April; 24(3): 188-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774538&dopt=Abstract
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Oxytocin affects the release of steroids, insulin-like growth factor-I, prostaglandin F2alpha and cyclic nucleotides by human granulosa cells in vitro. Author(s): Sirotkin AV, Schaeffer HJ, Mlyncek M, Missik J, Bulla J. Source: Human Reproduction (Oxford, England). 1996 January; 11(1): 152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8671178&dopt=Abstract
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Pachydermodactily as a cause of painful swelling of the knuckles: successful treatment with intralesional steroids. Author(s): Bondeson J. Source: Clin Exp Rheumatol. 2001 July-August; 19(4): 481-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491517&dopt=Abstract
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Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids. Author(s): Singer CF, Marbaix E, Kokorine I, Lemoine P, Donnez J, Eeckhout Y, Courtoy PJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 1997 September 16; 94(19): 10341-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9294212&dopt=Abstract
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Parturition: steroids, prostaglandin E2, and expression of adhesion molecules by endothelial cells. Author(s): Winkler M, Kemp B, Hauptmann S, Rath W. Source: Obstetrics and Gynecology. 1997 March; 89(3): 398-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9052593&dopt=Abstract
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Patient preferences and satisfaction with prescribed nasal steroids for allergic rhinitis. Author(s): Kaliner MA. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2001 November-December; 22(6 Suppl 1): S11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775399&dopt=Abstract
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Pediatric renal transplantation without steroids. Author(s): Birkeland SA, Larsen KE, Rohr N. Source: Pediatric Nephrology (Berlin, Germany). 1998 February; 12(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9543361&dopt=Abstract
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Perioperative and postoperative use of antibiotics and steroids in strabismus surgery. Author(s): Campolattaro BN, Olitsky MS, Rogers GL. Source: Journal of Pediatric Ophthalmology and Strabismus. 2001 September-October; 38(5): 304-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587179&dopt=Abstract
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Perioperative steroids for secondary adrenal insufficiency. Author(s): Blavin LR, French L. Source: The Journal of Family Practice. 1997 June; 44(6): 532-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9191621&dopt=Abstract
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Perioperative stress dose steroids: do they make a difference? Author(s): Brown CJ, Buie WD. Source: Journal of the American College of Surgeons. 2001 December; 193(6): 678-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768685&dopt=Abstract
Studies 219
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Peripheral arterial thrombosis in two young men using anabolic steroids. Author(s): Falkenberg M, Karlsson J, Ortenwall P. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 1997 February; 13(2): 223-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9091161&dopt=Abstract
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Permeation of steroids through human skin. Author(s): Johnson ME, Blankschtein D, Langer R. Source: Journal of Pharmaceutical Sciences. 1995 September; 84(9): 1144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8537898&dopt=Abstract
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Perspectives on the relationship of adrenal steroids to rheumatoid arthritis. Author(s): Masi AT, Chatterton RT, Aldag JC, Malamet RL. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 1-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114253&dopt=Abstract
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Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulindependent diabetes mellitus. Author(s): Petersen KR. Source: Dan Med Bull. 2002 February; 49(1): 43-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894723&dopt=Abstract
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Pharmacoeconomics of therapy for ITP: steroids, i.v.Ig, anti-D, and splenectomy. Author(s): Adams JR, Nathan DP, Bennett CL. Source: Blood Reviews. 2002 March; 16(1): 65-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913999&dopt=Abstract
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Physician prescribing practices: the role of patient preference in the selection of nasal steroids. Author(s): Kaliner MA. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2001 November-December; 22(6 Suppl 1): S17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775400&dopt=Abstract
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Physicochemical properties and transport of steroids across Caco-2 cells. Author(s): Faassen F, Kelder J, Lenders J, Onderwater R, Vromans H. Source: Pharmaceutical Research. 2003 February; 20(2): 177-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636155&dopt=Abstract
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Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. A placebo-controlled randomized trial. Author(s): Schols AM, Soeters PB, Mostert R, Pluymers RJ, Wouters EF. Source: American Journal of Respiratory and Critical Care Medicine. 1995 October; 152(4 Pt 1): 1268-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7551381&dopt=Abstract
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Plasma and urine levels of C18, C19 and C21 steroids in an asynchronous fish, the tilapia Oreochromis mossambicus (Teleostei, Cichlidae). Author(s): Rocha MJ, Reis-Henriques MA. Source: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1996 November; 115(3): 257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9375364&dopt=Abstract
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Plasma concentrations of neuroactive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Padberg F, di Michele F, Zwanzger P, Romeo E, Bernardi G, Schule C, Baghai TC, Ella R, Pasini A, Rupprecht R. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 November; 27(5): 874-8. Erratum In: Neuropsychopharmacology. 2003 March; 28(3): 610-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431862&dopt=Abstract
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Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid. Author(s): Bleach EC, Glencross RG, Feist SA, Groome NP, Knight PG. Source: Biology of Reproduction. 2001 March; 64(3): 743-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207187&dopt=Abstract
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Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa. Author(s): Monteleone P, Luisi M, Colurcio B, Casarosa E, Monteleone P, Ioime R, Genazzani AR, Maj M. Source: Psychosomatic Medicine. 2001 January-February; 63(1): 62-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11211066&dopt=Abstract
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Plasma substance-P and substance-K and gonadal steroids in relation to the gonadotropin surge in normal human reproductive cycles. Author(s): Mohyi DL, Kerdelhue B, Lenoir V, Kolm P, Jones HW Jr, Jones GS. Source: Journal of Assisted Reproduction and Genetics. 1998 October; 15(9): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9822983&dopt=Abstract
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Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women. Author(s): Hedstrom M, Sjoberg K, Brosjo E, Astrom K, Sjoberg H, Dalen N. Source: The Journal of Bone and Joint Surgery. British Volume. 2002 May; 84(4): 497-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043767&dopt=Abstract
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Positive temporal artery biopsy in a patient on therapeutic doses of steroids for six years. Author(s): Murgatroyd H, Milne A. Source: Eye (London, England). 2001 April; 15(Pt 2): 250-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339613&dopt=Abstract
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Possible role of corticosteroids in nervous system plasticity: improvement in amblyopia after optic neuritis in the fellow eye treated with steroids. Author(s): Constantinescu CS, Gottlob I. Source: Neurorehabilitation and Neural Repair. 2001; 15(3): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944744&dopt=Abstract
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Post-menopausal changes and dementing illness: ovarian steroids as the causal link? Author(s): Costa A, Nappi RE, Sinforiani E, Mauri M, Bernasconi L, Nappi G. Source: Aging (Milano). 1997; 9(4 Suppl): 66-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9358891&dopt=Abstract
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Postnatal steroids and neurodevelopmental outcomes: a problem in the making. Author(s): Barrington KJ. Source: Pediatrics. 2001 June; 107(6): 1425-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389269&dopt=Abstract
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Postnatal steroids to treat or prevent chronic lung disease in preterm infants. Author(s): Burchfield DJ. Source: Pediatrics. 2003 January; 111(1): 221-2; Author Reply 221-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509584&dopt=Abstract
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Postnatal steroids: a dilemma for the neonatologist. Author(s): Halliday HL. Source: Acta Paediatrica (Oslo, Norway : 1992). 2001 February; 90(2): 116-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11236036&dopt=Abstract
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Potential clinical uses of neuroactive steroids. Author(s): Zorumski CF, Mennerick S, Isenberg KE, Covey DF. Source: Curr Opin Investig Drugs. 2000 November; 1(3): 360-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11249720&dopt=Abstract
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Potential roles for gonadal steroids and insulin-like growth factor I during final cervical ripening. Author(s): Stjernholm Y, Sahlin L, Malmstrom A, Barchan K, Eriksson HA, Ekman G. Source: Obstetrics and Gynecology. 1997 September; 90(3): 375-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9277647&dopt=Abstract
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Practice parameter: Steroids, acyclovir, and surgery for Bell's palsy (an evidencebased review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Author(s): Grogan PM, Gronseth GS. Source: Neurology. 2001 April 10; 56(7): 830-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294918&dopt=Abstract
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Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): is there a link with infant survivorship and maternal behavior? Author(s): Fite JE, French JA. Source: Hormones and Behavior. 2000 August; 38(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924281&dopt=Abstract
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Preemies on steroids: a new iatrogenic disaster? Author(s): Harrison H. Source: Birth (Berkeley, Calif.). 2001 March; 28(1): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264630&dopt=Abstract
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Prematurity--steroids for all. Author(s): Main EK. Source: The Western Journal of Medicine. 1996 December; 165(6): 372-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9000858&dopt=Abstract
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Pre-menstrual steroids. Author(s): Smith SS. Source: Cellular and Molecular Life Sciences : Cmls. 2001 August; 58(9): 1263-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577983&dopt=Abstract
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Premenstrual syndrome, neuroactive steroids and the brain. Author(s): Sundstrom I, Backstrom T, Wang M, Olsson T, Seippel L, Bixo M. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1999 June; 13(3): 206-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10451814&dopt=Abstract
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Preoperative administration of steroids: influence on adhesion molecules and cytokines after cardiopulmonary bypass. Author(s): Schurr UP, Zund G, Hoerstrup SP, Grunenfelder J, Maly FE, Vogt PR, Turina MI. Source: The Annals of Thoracic Surgery. 2001 October; 72(4): 1316-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603453&dopt=Abstract
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Preoperative antibiotics and steroids in vestibular schwannoma excision. Author(s): Welling DB, Thomas R, Slater P, Daniels RL, Goodman JH. Source: The Laryngoscope. 1999 July; 109(7 Pt 1): 1081-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401845&dopt=Abstract
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Preoperative steroids confuse the diagnosis of allergic fungal sinusitis. Author(s): Graham SM, Ballas ZK. Source: The Journal of Allergy and Clinical Immunology. 1998 January; 101(1 Pt 1): 13940. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449519&dopt=Abstract
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Prescribing of beta-2 agonists and inhaled steroids in England: trends between 1992 and 1998, and association with material deprivation, chronic illness and asthma mortality rates. Author(s): Majeed A, Ferguson J, Field J. Source: Journal of Public Health Medicine. 1999 December; 21(4): 395-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469360&dopt=Abstract
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Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics. Author(s): Lewis DF, Brody K, Edwards MS, Brouillette RM, Burlison S, London SN. Source: Obstetrics and Gynecology. 1996 November; 88(5): 801-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885917&dopt=Abstract
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Prevalence of reduced bone mineral density in systemic lupus erythematosus and the role of steroids. Author(s): Kipen Y, Buchbinder R, Forbes A, Strauss B, Littlejohn G, Morand E. Source: The Journal of Rheumatology. 1997 October; 24(10): 1922-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9330933&dopt=Abstract
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Preventing labyrinthitis ossificans: the role of steroids. Author(s): Hartnick CJ, Kim HY, Chute PM, Parisier SC. Source: Archives of Otolaryngology--Head & Neck Surgery. 2001 February; 127(2): 1803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11177035&dopt=Abstract
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Prevention of leg length discrepancy in young children with pauciarticular juvenile rheumatoid arthritis by treatment with intraarticular steroids. Author(s): Sherry DD, Stein LD, Reed AM, Schanberg LE, Kredich DW. Source: Arthritis and Rheumatism. 1999 November; 42(11): 2330-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10555028&dopt=Abstract
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Primum non nocere: Should adults with idiopathic FSGS receive steroids? Author(s): Franceschini N, Hogan SL, Falk RJ. Source: Semin Nephrol. 2003 March; 23(2): 229-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704583&dopt=Abstract
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Pro/con clinical debate: are steroids useful in the management of patients with septic shock? Author(s): Ritacca FV, Simone C, Wax R, Craig KG, Walley KR. Source: Critical Care (London, England). 2002 April; 6(2): 113-6. Epub 2002 February 06. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983034&dopt=Abstract
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Production of interleukin-6 in human osteoblasts and human bone marrow stromal cells: evidence that induction by interleukin-1 and tumor necrosis factor-alpha is not regulated by ovarian steroids. Author(s): Rifas L, Kenney JS, Marcelli M, Pacifici R, Cheng SL, Dawson LL, Avioli LV. Source: Endocrinology. 1995 September; 136(9): 4056-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7649114&dopt=Abstract
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Production of steroids by human ovarian surface epithelial cells in culture: possible role of progesterone as growth inhibitor. Author(s): Ivarsson K, Sundfeldt K, Brannstrom M, Janson PO. Source: Gynecologic Oncology. 2001 July; 82(1): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426972&dopt=Abstract
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Production of steroids from human cumulus cells treated with different concentrations of gonadotropins during culture in vitro. Author(s): Chian RC, Ao A, Clarke HJ, Tulandi T, Tan SL. Source: Fertility and Sterility. 1999 January; 71(1): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9935117&dopt=Abstract
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Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Author(s): Parmar JS, Howell T, Kelly J, Bilton D. Source: Thorax. 2002 August; 57(8): 749-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149540&dopt=Abstract
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Progressive multifocal leukoencephalopathy (PML) in a patient with silicosis treated previously with steroids. A report of a case with JC virus infection confirmed immunohistochemically and by electron microscopy. Author(s): Adamek D, Kaluza J, Tomik B, Wyrwicz-Petkow U, Szczudlik A. Source: Pol J Pathol. 2000; 51(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10974934&dopt=Abstract
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Pro-inflammatory role of serotonin and interleukin-6 in arthritis and spondyloarthropathies--measurement of disease activity by bone scan and effect of steroids. Author(s): Pichler R, Maschek W, Krieglsteiner S, Raml A, Schmekal B, Berg J. Source: Scandinavian Journal of Rheumatology. 2002; 31(1): 41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922199&dopt=Abstract
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Promoter- and cell-specific responses to sex steroids. Author(s): Milgrom E, Savouret JF, Mantel A, Perrot-Applanat M, Delabre K, Lescop P. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1997; 7 Suppl 1: S23-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9205642&dopt=Abstract
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Propylthiouracil-induced acute interstitial nephritis with acute renal failure requiring haemodialysis: successful therapy with steroids. Author(s): Fang JT, Huang CC. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998 March; 13(3): 757-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9550661&dopt=Abstract
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Prospective echocardiographic assessment of androgenic-anabolic steroids effects on cardiac structure and function in strength athletes. Author(s): Hartgens F, Cheriex EC, Kuipers H. Source: International Journal of Sports Medicine. 2003 July; 24(5): 344-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868045&dopt=Abstract
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Prospective randomized controlled multicenter trial on steroids plus ramipril in proteinuric IgA nephropathy. Author(s): Manno C, Gesualdo L, D'Altri C, Rossini M, Grandaliano G, Schena FP. Source: Journal of Nephrology. 2001 July-August; 14(4): 248-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506246&dopt=Abstract
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Prospective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clamping. Author(s): Muratore A, Ribero D, Ferrero A, Bergero R, Capussotti L. Source: The British Journal of Surgery. 2003 January; 90(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520569&dopt=Abstract
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Proximal myopathy associated with inhaled steroids. Author(s): Herzog AG. Source: Jama : the Journal of the American Medical Association. 1999 January 6; 281(1): 37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9892448&dopt=Abstract
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Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase. Author(s): Gangloff A, Shi R, Nahoum V, Lin SX. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 February; 17(2): 274-6. Epub 2002 December 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490543&dopt=Abstract
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Psychiatric effects of anabolic steroids after burn injuries. Author(s): Morton R, Gleason O, Yates W. Source: Psychosomatics. 2000 January-February; 41(1): 66-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665271&dopt=Abstract
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Psychological and behavioural effects of endogenous testosterone and anabolicandrogenic steroids. An update. Author(s): Bahrke MS, Yesalis CE 3rd, Wright JE. Source: Sports Medicine (Auckland, N.Z.). 1996 December; 22(6): 367-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8969015&dopt=Abstract
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Psychological disorder in asthma is associated with poor control and poor adherence to inhaled steroids. Author(s): Cluley S, Cochrane GM. Source: Respiratory Medicine. 2001 January; 95(1): 37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207015&dopt=Abstract
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Psychoneuroendocrine aspects of temporolimbic epilepsy. Part I. Brain, reproductive steroids, and emotions. Author(s): Herzog AG. Source: Psychosomatics. 1999 March-April; 40(2): 95-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100430&dopt=Abstract
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Psychoneuroendocrine aspects of temporolimbic epilepsy. Part II: Epilepsy and reproductive steroids. Author(s): Herzog AG. Source: Psychosomatics. 1999 March-April; 40(2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100431&dopt=Abstract
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Pulmonary amyloidosis: treatment with laser therapy and systemic steroids. Author(s): Nugent AM, Elliott H, McGuigan JA, Varghese G. Source: Respiratory Medicine. 1996 August; 90(7): 433-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8796238&dopt=Abstract
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Pulmonary tuberculosis and steroids. Author(s): Clarke P, Allen MB. Source: Chest. 1996 February; 109(2): 582. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8620747&dopt=Abstract
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Pulsatile release of sex steroids? A hypothesis to explain anomalies in hormonal therapy. Author(s): Wren BG. Source: Climacteric : the Journal of the International Menopause Society. 2000 March; 3(1): 68-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910613&dopt=Abstract
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Pulse dexamethasone, oral steroids and azathioprine in the management of erythema nodosum leprosum. Author(s): Mahajan VK, Sharma NL, Sharma RC, Sharma A. Source: Lepr Rev. 2003 June; 74(2): 171-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862259&dopt=Abstract
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Pulse steroids for ulcerative colitis: good news, bad news, and no news. Author(s): Sachar DB. Source: Journal of Clinical Gastroenterology. 2002 October; 35(4): 291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352289&dopt=Abstract
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Pure red cell aplasia after ABO-incompatible allogeneic stem cell transplantation in severe aplastic anemia with response to steroids: a case report and literature review. Author(s): Yang MH, Hsu HC. Source: Annals of Hematology. 2001 May; 80(5): 299-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446734&dopt=Abstract
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QT interval and QT dispersion in endurance athletes and in power athletes using large doses of anabolic steroids. Author(s): Stolt A, Karila T, Viitasalo M, Mantysaari M, Kujala UM, Karjalainen J. Source: The American Journal of Cardiology. 1999 August 1; 84(3): 364-6, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496458&dopt=Abstract
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Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: results of a prospective, randomized trial. Author(s): Neuhaus P, Klupp J, Langrehr JM, Neumann U, Gebhardt A, Pratschke J, Tullius SG, Lohmann R, Radke C, Rayes N, Neuhaus R, Bechstein WO. Source: Transplantation. 2000 June 15; 69(11): 2343-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10868638&dopt=Abstract
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Qualitative description of the prevalence and use of anabolic androgenic steroids by United States powerlifters. Author(s): Curry LA, Wagman DF. Source: Percept Mot Skills. 1999 February; 88(1): 224-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10214647&dopt=Abstract
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Quantitation of cortisol and related 3-oxo-4-ene steroids in urine using gas chromatography/mass spectrometry with stable isotope-labeled internal standards. Author(s): Palermo M, Gomez-Sanchez C, Roitman E, Shackleton CH. Source: Steroids. 1996 October; 61(10): 583-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8910971&dopt=Abstract
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Quantitative evaluation of the influence of ovarian steroids on plasminogen activators and inhibitors in human endometrial cells and trophoblasts. Author(s): Ueyama M, Kasatori N, Urayama T, Maemura T, Yao Y, Shiraishi T, Saito S, Kubo H. Source: Thrombosis Research. 2002 November 25; 108(4): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617987&dopt=Abstract
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Quantitative structure-activity relationships in a series of endogenous and synthetic steroids exhibiting induction of CYP3A activity and hepatomegaly associated with increased DNA synthesis. Author(s): Lewis DF, Ioannides C, Parke DV, Schulte-Hermann R. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2000 November 15; 74(4): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11162923&dopt=Abstract
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Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3. Author(s): Noyes WR, Rodriguez R, Knechtle SJ, Pirsch JD, Sollinger HW, D'Alessandro AM, Chappell R, Belzer FO, Kinsella TJ. Source: International Journal of Radiation Oncology, Biology, Physics. 1996 March 15; 34(5): 1055-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8600088&dopt=Abstract
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Radiation-induced mammary tumors in virgin and parous rats administered contraceptive steroids, 17alpha-ethinylestradiol and norethisterone. Author(s): Inano H, Onoda M, Suzuki K, Kobayashi H, Wakabayashi K. Source: Carcinogenesis. 2000 May; 21(5): 1043-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783331&dopt=Abstract
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Radiotherapy without steroids in selected metastatic spinal cord compression patients. A phase II trial. Author(s): Maranzano E, Latini P, Beneventi S, Perruci E, Panizza BM, Aristei C, Lupattelli M, Tonato M. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1996 April; 19(2): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8610645&dopt=Abstract
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Raised cortisol excretion rate in urine and contamination by topical steroids. Author(s): Kelly CJ, Ogilvie A, Evans JR, Shapiro D, Wallace AM, Davies DL. Source: Bmj (Clinical Research Ed.). 2001 March 10; 322(7286): 594. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238157&dopt=Abstract
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Rapid actions of steroids. Focus on “Nongenomic regulation of ENaC by aldosterone”. Author(s): Halm DR. Source: American Journal of Physiology. Cell Physiology. 2001 October; 281(4): C1094-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11546644&dopt=Abstract
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Rapid discontinuation of steroids in living donor kidney transplantation: a pilot study. Author(s): Matas AJ, Ramcharan T, Paraskevas S, Gillingham KJ, Dunn DL, Gruessner RW, Humar A, Kandaswamy R, Najarian JS, Payne WD, Sutherland DE. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2001 September; 1(3): 278-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102262&dopt=Abstract
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Rapid effect of inhaled steroids on nocturnal worsening of asthma. Author(s): Frezza G, Terra-Filho J, Martinez JA, Vianna EO. Source: Thorax. 2003 July; 58(7): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832684&dopt=Abstract
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Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription. Author(s): Watters JJ, Campbell JS, Cunningham MJ, Krebs EG, Dorsa DM. Source: Endocrinology. 1997 September; 138(9): 4030-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9275096&dopt=Abstract
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Rapid non-genomic vasodilator actions of oestrogens and sex steroids. Author(s): Ruehlmann DO, Mann GE. Source: Current Medicinal Chemistry. 2000 May; 7(5): 533-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10702623&dopt=Abstract
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Rapid transbilayer movement of spin-labeled steroids in human erythrocytes and in liposomes. Author(s): Muller P, Herrmann A. Source: Biophysical Journal. 2002 March; 82(3): 1418-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867457&dopt=Abstract
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Rapid weaning from mechanical ventilator in acute cervical cord multiple sclerosis lesion after steroids. Author(s): Pittock SJ, Rodriguez M, Wijdicks EF. Source: Anesthesia and Analgesia. 2001 December; 93(6): 1550-1, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726441&dopt=Abstract
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Reasons why some children receiving tacrolimus therapy require steroids more than 5 years post liver transplantation. Author(s): Jain A, Mazariegos G, Kashyap R, Marsh W, Khanna A, Iurlano K, Fung J, Reyes J. Source: Pediatric Transplantation. 2001 April; 5(2): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328546&dopt=Abstract
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Rectal steroids suppress bone formation in patients with colitis. Author(s): Robinson RJ, Iqbal SJ, Whitaker RP, Abrams K, Mayberry JF. Source: Alimentary Pharmacology & Therapeutics. 1997 February; 11(1): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9042994&dopt=Abstract
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Recurring staphylococcal scalded skin syndrome-like bullous mastocytosis: the utility of cytodiagnosis and the rapid regression with steroids. Author(s): Has C, Misery L, David L, Cambazard F. Source: Pediatric Dermatology. 2002 May-June; 19(3): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047641&dopt=Abstract
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Reduced androgen levels in adult turner syndrome: influence of female sex steroids and growth hormone status. Author(s): Hojbjerg Gravholt C, Svenstrup B, Bennett P, Sandahl Christiansen J. Source: Clinical Endocrinology. 1999 June; 50(6): 791-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468952&dopt=Abstract
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Reduced free IGF-I and increased IGFBP-3 proteolysis in Turner syndrome: modulation by female sex steroids. Author(s): Gravholt CH, Frystyk J, Flyvbjerg A, Orskov H, Christiansen JS. Source: American Journal of Physiology. Endocrinology and Metabolism. 2001 February; 280(2): E308-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158935&dopt=Abstract
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Reducing the post-pump syndrome by using heparin-coated circuits, steroids, or aprotinin. Author(s): Harig F, Feyrer R, Mahmoud FO, Blum U, von der Emde J. Source: The Thoracic and Cardiovascular Surgeon. 1999 April; 47(2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10363611&dopt=Abstract
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Refining the use of inhaled steroids in asthma. Author(s): Miles J. Source: Hosp Med. 2000 August; 61(8): 558-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045225&dopt=Abstract
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Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans. Author(s): Chan JL, Bluher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS. Source: Diabetes. 2002 July; 51(7): 2105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086939&dopt=Abstract
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Regulation of EGF-induced tenascin-C by steroids in tenascin-C-non-producing human carcinoma cells. Author(s): Sakai T, Kawakatsu H, Furukawa Y, Saito M. Source: International Journal of Cancer. Journal International Du Cancer. 1995 November 27; 63(5): 720-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7591291&dopt=Abstract
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Regulation of epidermal growth factor receptor synthesis by ovarian steroids in human endometrial cells in culture. Author(s): Watson H, Franks S, Bonney RC. Source: Journal of Reproduction and Fertility. 1996 July; 107(2): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882285&dopt=Abstract
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Regulation of placental corticotropin-releasing hormone by steroids. Possible implications in labor initiation. Author(s): Karalis K, Majzoub JA. Source: Annals of the New York Academy of Sciences. 1995 December 29; 771: 551-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8597430&dopt=Abstract
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Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques. Author(s): Pecins-Thompson M, Brown NA, Bethea CL. Source: Brain Research. Molecular Brain Research. 1998 January; 53(1-2): 120-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9473622&dopt=Abstract
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Regulation of the 24h body temperature rhythm of women in luteal phase: role of gonadal steroids and prostaglandins. Author(s): Cagnacci A, Arangino S, Tuveri F, Paoletti AM, Volpe A. Source: Chronobiology International. 2002 July; 19(4): 721-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182499&dopt=Abstract
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Regulation of the expression of the angiogenic enzyme platelet-derived endothelial cell growth factor/thymidine phosphorylase in endometrial isolates by ovarian steroids and cytokines. Author(s): Zhang L, Mackenzie IZ, Rees MC, Bicknell R. Source: Endocrinology. 1997 November; 138(11): 4921-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348223&dopt=Abstract
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Relationship between urinary profile of the endogenous steroids and postmenopausal women with stress urinary incontinence. Author(s): Bai SW, Jung BH, Chung BC, Kim SU, Kim JY, Rha KH, Cho JS, Park YW, Park KH. Source: Neurourology and Urodynamics. 2003; 22(3): 198-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707870&dopt=Abstract
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Relationships between age-related changes of sex steroids, obesity and body fat distribution among healthy Polish males. Author(s): Jankowska EA, Rogucka E, Medras M, Welon Z. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 November-December; 6(6): 1159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208473&dopt=Abstract
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Relationships between glucocorticoids and gonadal steroids in rheumatoid arthritis. Author(s): da Silva JA. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 158-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114269&dopt=Abstract
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Relative sensitivity of Tc-99m WBC versus In-111 WBC in a patient with Crohn's disease on steroids. Author(s): Lyons KP, Challa S, Broekelschen P, Milne N. Source: Clinical Nuclear Medicine. 1997 June; 22(6): 359-62. Erratum In: Clin Nucl Med 1997 December; 22(12): 875. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9193803&dopt=Abstract
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Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural alphagalactosyl IgG antibodies. Author(s): Manez R, Blanco FJ, Diaz I, Centeno A, Lopez-Pelaez E, Hermida M, Davies HF, Katopodis A. Source: Xenotransplantation. 2001 February; 8(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208187&dopt=Abstract
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Renal effects of antenatally or postnatally administered steroids. Author(s): Cattarelli D, Chirico G, Simeoni U. Source: Pediatr Med Chir. 2002 March-April; 24(2): 157-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987524&dopt=Abstract
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Renal transplantation: can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol biopsy findings. Author(s): Gotti E, Perico N, Perna A, Gaspari F, Cattaneo D, Caruso R, Ferrari S, Stucchi N, Marchetti G, Abbate M, Remuzzi G. Source: Journal of the American Society of Nephrology : Jasn. 2003 March; 14(3): 755-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595513&dopt=Abstract
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Reoccurrence of culture-positive pertussis in an infant initially treated with azithromycin and steroids. Author(s): Steinberg JM, Srugo I. Source: Archives of Pediatrics & Adolescent Medicine. 2002 October; 156(10): 1057-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361458&dopt=Abstract
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Repeated antenatal steroids: size at birth and subsequent development. Author(s): Lampe JB, Touch SM, Spitzer AR. Source: Clinical Pediatrics. 1999 September; 38(9): 553-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500892&dopt=Abstract
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Repeated courses of steroids in preterm membrane rupture do not increase the risk of histologic chorioamnionitis. Author(s): Ghidini A, Salafia CM, Minior VK. Source: American Journal of Perinatology. 1997 July; 14(6): 309-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9217948&dopt=Abstract
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Resistance to multiple steroids in two sisters. Author(s): New MI, Nimkarn S, Brandon DD, Cunningham-Rundles S, Wilson RC, Newfield RS, Vandermeulen J, Barron N, Russo C, Loriaux DL, O'Malley B. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 JanuaryMarch; 76(1-5): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384874&dopt=Abstract
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Resistance to several steroids in two sisters. Author(s): New MI, Nimkarn S, Brandon DD, Cunningham-Rundles S, Wilson RC, Newfield RS, Vandermeulen J, Barron N, Russo C, Loriaux DL, O'Malley B. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 December; 84(12): 4454-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599702&dopt=Abstract
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Resistance trained athletes using or not using anabolic steroids compared to runners: effects on cardiorespiratory variables, body composition, and plasma lipids. Author(s): Yeater R, Reed C, Ullrich I, Morise A, Borsch M. Source: British Journal of Sports Medicine. 1996 March; 30(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8665108&dopt=Abstract
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Resolution of hydrops in twin-twin transfusion syndrome: could steroids have a role? Author(s): Scott F, Hind F, Boogert A. Source: Prenatal Diagnosis. 1997 May; 17(5): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9178323&dopt=Abstract
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Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Author(s): MacMillan ML, Weisdorf DJ, Wagner JE, DeFor TE, Burns LJ, Ramsay NK, Davies SM, Blazar BR. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2002; 8(7): 387-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171485&dopt=Abstract
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Response of vulvar lichen sclerosus and squamous cell hyperplasia to graduated topical steroids. Author(s): Clark TJ, Etherington IJ, Luesley DM. Source: J Reprod Med. 1999 November; 44(11): 958-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589407&dopt=Abstract
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Response to plasma exchange and steroids as combined therapy for patients with thrombotic thrombocytopenic purpura. Author(s): de la Rubia J, Lopez A, Arriaga F, Cid AR, Vicente AI, Marty ML, Sanz MA. Source: Acta Haematologica. 1999; 102(1): 12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473882&dopt=Abstract
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Response to steroids in de novo autoimmune hepatitis after liver transplantation. Author(s): Salcedo M, Vaquero J, Banares R, Rodriguez-Mahou M, Alvarez E, Vicario JL, Hernandez-Albujar A, Tiscar JL, Rincon D, Alonso S, De Diego A, Clemente G. Source: Hepatology (Baltimore, Md.). 2002 February; 35(2): 349-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11826408&dopt=Abstract
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Responses to steroids and bronchodilators in COPD in the ISOLDE trial: the fat lady sings on. Author(s): Gross NJ. Source: Thorax. 2003 August; 58(8): 647-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885972&dopt=Abstract
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Results of photodynamic therapy for ablation of dysplasia and early cancer in Barrett's esophagus and effect of oral steroids on stricture formation. Author(s): Panjehpour M, Overholt BF, Haydek JM, Lee SG. Source: The American Journal of Gastroenterology. 2000 September; 95(9): 2177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007214&dopt=Abstract
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Resurrection of steroids for sepsis resuscitation. Author(s): Annane D. Source: Minerva Anestesiol. 2002 April; 68(4): 127-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024069&dopt=Abstract
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Retinoids and steroids regulate menstrual phase histological features in human endometrial organotypic cultures. Author(s): Kamelle S, Sienko A, Benbrook DM. Source: Fertility and Sterility. 2002 September; 78(3): 596-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215339&dopt=Abstract
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Retroperitoneal fibrosis and membranous nephropathy. Improvement of both diseases after treatment with steroids and immunosuppressive agents. Author(s): Moroni G, Farricciotti A, Cappelletti M, Ponticelli C. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 May; 14(5): 1303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10344388&dopt=Abstract
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Retroperitoneal fibrosis associated with membranous nephropathy effectively treated with steroids. Author(s): Shirota S, Tsuchiya K, Takada M, Komeda M, Oomae K, Ogawa T, Yumura W, Nitta K, Nihei H. Source: Intern Med. 2002 January; 41(1): 20-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838585&dopt=Abstract
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Retrospective analysis of 30 patients who underwent liver transplantation without use of steroids. Author(s): Tisone G, Angelico M, Orlando G, Palmieri GP, Strati F, Di Paolo D, Casciani CU. Source: Transplantation Proceedings. 1999 November; 31(7): 2908-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10578335&dopt=Abstract
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Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Author(s): Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O'Brien CA, Plotkin L, Fu Q, Mancino AT, Wen Y, Vertino AM, Powers CC, Stewart SA, Ebert R, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC. Source: Science. 2002 October 25; 298(5594): 843-6. Erratum In: Science. 2003 February 21; 299(5610): 1184. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399595&dopt=Abstract
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Reversed-phase high-performance liquid chromatographic screening method for serum steroids using retention index and diode-array detection. Author(s): Kuronen P, Volin P, Laitalainen T. Source: J Chromatogr B Biomed Sci Appl. 1998 November 6; 718(2): 211-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9840431&dopt=Abstract
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Reversed-phase high-performance liquid chromatography separation of adrenal steroids prior to radioimmunoassay: application in congenital adrenal hyperplasia. Author(s): Fernandes VT, Ribeiro-Neto LM, Lima SB, Vieira JG, Verreschi IT, Kater CE. Source: Journal of Chromatographic Science. 2003 May-June; 41(5): 251-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841953&dopt=Abstract
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Reversible azoospermia: anabolic steroids may profoundly affect human immunodeficiency virus-seropositive men undergoing assisted reproduction. Author(s): Pena JE, Thornton MH Jr, Sauer MV. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 2): 1073-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738106&dopt=Abstract
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Reversible paralysis with status asthmaticus, steroids, and pancuronium: clinical electrophysiological correlates. Author(s): Road J, Mackie G, Jiang TX, Stewart H, Eisen A. Source: Muscle & Nerve. 1997 December; 20(12): 1587-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9390673&dopt=Abstract
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Risk factors for lack of asthma self-management knowledge among ED patients not on inhaled steroids. Author(s): Radeos MS, Leak LV, Lugo BP, Hanrahan JP, Clark S, Camargo CA Jr; MARC Investigators. Source: The American Journal of Emergency Medicine. 2001 July; 19(4): 253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11447507&dopt=Abstract
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Risk/benefit ratio of inhaled steroids. Author(s): Skoner DP, Gentile D. Source: The Journal of Pediatrics. 1996 December; 129(6): 942-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8969744&dopt=Abstract
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Risks and benefits of steroids in preterm infants. Author(s): Doyle L, Davis P, Morley C. Source: The Journal of Pediatrics. 2001 May; 138(5): 784-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343066&dopt=Abstract
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Risky practices among people who inject steroids. Author(s): Delalande CL, Aitken CK, Mercuri P, Stanton KA. Source: The Medical Journal of Australia. 1998 July 6; 169(1): 62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9695708&dopt=Abstract
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Role of growth hormone and sex steroids in achieving and maintaining normal bone mass. Author(s): Holmes SJ, Shalet SM. Source: Hormone Research. 1996; 45(1-2): 86-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8742125&dopt=Abstract
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Role of steroids in croup and beta agonists in bronchiolitis. Author(s): Veerappan A, Kumar A. Source: Indian J Pediatr. 1996 September-October; 63(5): 577-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830025&dopt=Abstract
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Seminal plasma melatonin and gonadal steroids concentrations in normal men. Author(s): Luboshitzky R, Shen-Orr Z, Herer P. Source: Archives of Andrology. 2002 May-June; 48(3): 225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964216&dopt=Abstract
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Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities. Author(s): van Rensburg SJ, Potocnik FC, Kiss T, Hugo F, van Zijl P, Mansvelt E, Carstens ME, Theodorou P, Hurly PR, Emsley RA, Taljaard JJ. Source: Brain Research Bulletin. 2001 May 15; 55(2): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470334&dopt=Abstract
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Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression in asthmatic children treated with inhaled steroids. Author(s): Kannisto S, Korppi M, Remes K, Voutilainen R. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 4908-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600561&dopt=Abstract
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Serum eosinophil cationic protein (ECP) as a mediator of inflammation in acute asthma, during resolution and during the monitoring of stable asthmatic patients treated with inhaled steroids according to a dose reduction schedule. Author(s): Kunkel G, Ryden AC. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1999 February; 48(2): 94-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202995&dopt=Abstract
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Severe bacillus Calmette-Guerin cystitis responds to systemic steroids when antituberculous drugs and local steroids fail. Author(s): Wittes R, Klotz L, Kosecka U. Source: The Journal of Urology. 1999 May; 161(5): 1568-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210404&dopt=Abstract
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Severe Henoch-Schonlein nephritis: resolution with azathioprine and steroids. Author(s): Singh S, Devidayal, Kumar L, Joshi K, Minz RW, Datta U. Source: Rheumatology International. 2002 August; 22(4): 133-7. Epub 2002 July 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172950&dopt=Abstract
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Sex steroids and body composition in men with cystic fibrosis. Author(s): Leifke E, Friemert M, Heilmann M, Puvogel N, Smaczny C, von zur Muhlen A, Brabant G. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 May; 148(5): 551-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720539&dopt=Abstract
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Sex steroids and bone. Author(s): Manolagas SC, Kousteni S, Jilka RL. Source: Recent Progress in Hormone Research. 2002; 57: 385-409. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017554&dopt=Abstract
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Sex steroids and insulin resistance. Author(s): Livingstone C, Collison M. Source: Clinical Science (London, England : 1979). 2002 February; 102(2): 151-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834135&dopt=Abstract
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Sex steroids and sleep: sleep disturbances in menopause. Author(s): Polo-Kantola P. Source: Annales D'endocrinologie. 2003 April; 64(2): 152-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773953&dopt=Abstract
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Sex steroids, ANGELS and osteoporosis. Author(s): Moggs JG, Deavall DG, Orphanides G. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2003 March; 25(3): 195-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596222&dopt=Abstract
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Sex steroids, meibomian gland dysfunction and evaporative dry eye in Sjogren's syndrome. Author(s): Sullivan DA, Schaumberg DA, Suzuki T, Schirra F, Liu M, Richards S, Sullivan RM, Dana MR, Sullivan BD. Source: Lupus. 2002; 11(10): 667. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413064&dopt=Abstract
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Sex steroids, mice, and men: when androgens and estrogens get very close to each other. Author(s): Bilezikian JP. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 April; 17(4): 563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918214&dopt=Abstract
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Sex steroids, the meibomian gland and evaporative dry eye. Author(s): Sullivan DA, Yamagami H, Liu M, Steagall RJ, Schirra F, Suzuki T, Krenzer KL, Cermak JM, Sullivan RM, Richards SM, Schaumberg DA, Dana MR, Sullivan BD. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt A): 389-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613938&dopt=Abstract
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Short- and long-term efficacy of oral cyclophosphamide and steroids in patients with membranous nephropathy and renal insufficiency. Study Group. Author(s): Branten AJ, Wetzels JF. Source: Clinical Nephrology. 2001 July; 56(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499653&dopt=Abstract
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Sialic acid binding protein of human endometrium: its regulation by steroids. Author(s): Sen S, Chowdhury G, Chowdhury M. Source: Molecular and Cellular Biochemistry. 2001 May; 221(1-2): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506181&dopt=Abstract
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Slowly tapering off steroids protects the graft against hepatitis C recurrence after liver transplantation. Author(s): Brillanti S, Vivarelli M, De Ruvo N, Aden AA, Camaggi V, D'Errico A, Furlini G, Bellusci R, Roda E, Cavallari A. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 October; 8(10): 884-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360428&dopt=Abstract
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Solvent and solid-phase extraction of natural and synthetic anabolic steroids in human urine. Author(s): Gonzalo-Lumbreras R, Pimentel-Trapero D, Izqierdo-Hornillos R. Source: J Chromatogr B Biomed Sci Appl. 2001 April 25; 754(2): 419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339285&dopt=Abstract
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Species, sex and inter-individual differences in DNA repair induced by nine sex steroids in primary cultures of rat and human hepatocytes. Author(s): Martelli A, Mattioli F, Angiola M, Reimann R, Brambilla G. Source: Mutation Research. 2003 April 20; 536(1-2): 69-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694747&dopt=Abstract
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Specificity of human alcohol dehydrogenase 1C*2 (gamma2gamma2) for steroids and simulation of the uncompetitive inhibition of ethanol metabolism. Author(s): Plapp BV, Berst KB. Source: Chemico-Biological Interactions. 2003 February 1; 143-144: 183-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604203&dopt=Abstract
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Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Author(s): Farquhar C, Lee O, Toomath R, Jepson R. Source: Cochrane Database Syst Rev. 2001; (4): Cd000194. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687072&dopt=Abstract
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Stability of salivary steroids: the influences of storage, food and dental care. Author(s): Groschl M, Wagner R, Rauh M, Dorr HG. Source: Steroids. 2001 October; 66(10): 737-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522335&dopt=Abstract
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Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Author(s): Pritchett JW. Source: Clinical Orthopaedics and Related Research. 2001 May; (386): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347831&dopt=Abstract
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Statistics, not memories: what was the standard of care for administering antenatal steroids to women in preterm labor between 1985 and 2000? Author(s): Meadow WL, Bell A, Sunstein CR. Source: Obstetrics and Gynecology. 2003 August; 102(2): 356-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907113&dopt=Abstract
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Steroid treatment for myasthenia gravis: steroids are overutilized. Author(s): Rivner MH. Source: Muscle & Nerve. 2002 January; 25(1): 115-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754195&dopt=Abstract
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Steroid treatment for myasthenia gravis: steroids have an important role. Author(s): Bedlack RS, Sanders DB. Source: Muscle & Nerve. 2002 January; 25(1): 117-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754196&dopt=Abstract
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Steroids and cytokines in endometrial angiogenesis. Author(s): Kapiteijn K, Koolwijk P, Van Der Weiden R, Helmerhorst F, Kooistra T, Van Hinsbergh VW. Source: Anticancer Res. 2001 November-December; 21(6B): 4231-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908676&dopt=Abstract
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Steroids and risk of upper gastrointestinal complications. Author(s): Hernandez-Diaz S, Rodriguez LA. Source: American Journal of Epidemiology. 2001 June 1; 153(11): 1089-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390328&dopt=Abstract
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Steroids and the surgical patient. Author(s): Jabbour SA. Source: The Medical Clinics of North America. 2001 September; 85(5): 1311-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565501&dopt=Abstract
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Steroids cause osteoporosis. Author(s): Gordon MM, Stevenson S, Hunter JA. Source: Annals of the Rheumatic Diseases. 2002 October; 61(10): 947; Author Reply 9478. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228175&dopt=Abstract
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Steroids cause osteoporosis. Author(s): Paget S. Source: Annals of the Rheumatic Diseases. 2002 January; 61(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779746&dopt=Abstract
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Steroids fail to down-regulate respiratory syncytial virus-induced IL-8 secretion in infants. Author(s): Thomas LH, Sharland M, Friedland JS. Source: Pediatric Research. 2002 September; 52(3): 368-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193669&dopt=Abstract
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Steroids for acute spinal cord injury. Author(s): Bracken MB. Source: Cochrane Database Syst Rev. 2002; (3): Cd001046. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137616&dopt=Abstract
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Steroids for Crohn's disease--an appreciation and a vote of confidence. Author(s): Korelitz BI. Source: Inflammatory Bowel Diseases. 2002 May; 8(3): 219-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979144&dopt=Abstract
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Steroids for improving recovery following tonsillectomy in children. Author(s): Steward DL, Welge JA, Myer CM. Source: Cochrane Database Syst Rev. 2003; (1): Cd003997. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535500&dopt=Abstract
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Steroids for otitis media with effusion: a systematic review. Author(s): Butler CC, van Der Voort JH. Source: Archives of Pediatrics & Adolescent Medicine. 2001 June; 155(6): 641-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386950&dopt=Abstract
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Steroids for septic shock: back from the dead? (Con). Author(s): Sessler CN. Source: Chest. 2003 May; 123(5 Suppl): 482S-9S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740233&dopt=Abstract
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Steroids for septic shock: back from the dead? (Pro). Author(s): Balk RA. Source: Chest. 2003 May; 123(5 Suppl): 490S-9S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740234&dopt=Abstract
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Steroids in arms: science, government, industry, and the hormones of the adrenal cortex in the United States, 1930-1950. Author(s): Rasmussen N. Source: Medical History. 2002 July; 46(3): 299-324. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194423&dopt=Abstract
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Steroids in perinatology. Author(s): Locham KK, Sodhi M, Jindal G. Source: Indian Pediatrics. 2002 November; 39(11): 1075-7; Author Reply 1078-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466592&dopt=Abstract
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Steroids in perinatology. Author(s): Narayan S, Deorari AK. Source: Indian Pediatrics. 2002 April; 39(4): 347-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11976464&dopt=Abstract
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Steroids in sepsis--more effective than activated protein C? Author(s): Bradley C. Source: Intensive & Critical Care Nursing : the Official Journal of the British Association of Critical Care Nurses. 2001 August; 17(4): 242-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868733&dopt=Abstract
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Steroids in the nervous system: a Pandora's box? Author(s): Melcangi RC, Panzica G. Source: Trends in Neurosciences. 2001 June; 24(6): 311-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421230&dopt=Abstract
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Steroids may compromise quality of life of renal transplant recipients on a tacrolimus-based regimen. Author(s): Moons P, Vanrenterghem Y, van Hooff JP, Squifflet JP, Margodt D, Mullens M, Thevissen I, De Geest S. Source: Transplantation Proceedings. 2002 August; 34(5): 1691-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176538&dopt=Abstract
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Steroids treatment of granulomatous hepatitis complicating Coxiella burnetii acute infection. Author(s): Crespo M, Sopena B, Bordon J, de la Fuente J, Rubianes M, Martinez-Vazquez C. Source: Infection. 1999 March-April; 27(2): 132-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219646&dopt=Abstract
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Steroids withdrawal after 3 months of successful renal transplantation using a tacrolimus- and mycophenolate-based immunosuppression. Author(s): Alarcon-Zurita A, Munar MA, Losada P, Morey A, Martinez J, de la Prada FJ, Marco J. Source: Transplantation Proceedings. 2002 February; 34(1): 118-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959216&dopt=Abstract
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Steroids, carbogen or placebo for sudden hearing loss: a prospective double-blind study. Author(s): Cinamon U, Bendet E, Kronenberg J. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2001 November; 258(9): 477-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769996&dopt=Abstract
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Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: a systematic review. Author(s): Rowell NP, Gleeson FV. Source: Clin Oncol (R Coll Radiol). 2002 October; 14(5): 338-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555872&dopt=Abstract
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Steroids, retinoids, and wound healing. Author(s): Anstead GM. Source: Adv Wound Care. 1998 October; 11(6): 277-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326344&dopt=Abstract
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Steroids. Author(s): Riad M, Mogos M, Thangathurai D, Lumb PD. Source: Current Opinion in Critical Care. 2002 August; 8(4): 281-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386486&dopt=Abstract
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Steroids: youth at risk. Author(s): Ungerleider S. Source: The Harvard Mental Health Letter / from Harvard Medical School. 2001 May; 17(11): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410446&dopt=Abstract
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Stress and neuroactive steroids. Author(s): Barbaccia ML, Serra M, Purdy RH, Biggio G. Source: Int Rev Neurobiol. 2001; 46: 243-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599302&dopt=Abstract
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Structure-activity relationship of aza-steroids as PI-PLC inhibitors. Author(s): Xie W, Peng H, Kim DI, Kunkel M, Powis G, Zalkow LH. Source: Bioorganic & Medicinal Chemistry. 2001 May; 9(5): 1073-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377165&dopt=Abstract
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SubTenon's infusion of steroids for treatment of orbital hemangiomas. Author(s): Coats DK, O'Neil JW, D'Elia VJ, Brady-McCreery KM, Paysse EA. Source: Ophthalmology. 2003 June; 110(6): 1255-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799256&dopt=Abstract
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Successful treatment with steroids of upper gastrointestinal acute graft vs. host disease after hematopoietic stem cell transplantation. Author(s): Nishi T, Okazaki K, Fujii S, Uchida K, Uose S, Nakase H, Ohana M, Nishihara T, Chiba T. Source: Endoscopy. 2001 November; 33(11): 985-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668409&dopt=Abstract
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Synthesis of cytotoxic 6E-hydroximino-4-ene steroids: structure/activity studies. Author(s): Deive N, Rodriguez J, Jimenez C. Source: Journal of Medicinal Chemistry. 2001 August 2; 44(16): 2612-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472215&dopt=Abstract
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Systemic activity of inhaled steroids in 1- to 3-year-old children with asthma. Author(s): Anhoj J, Bisgaard AM, Bisgaard H. Source: Pediatrics. 2002 March; 109(3): E40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875168&dopt=Abstract
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Systemic effects of inhaled steroids. Author(s): McKenzie SA. Source: Thorax. 2001 December; 56(12): 981. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758509&dopt=Abstract
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Systemic effects of inhaled steroids. Author(s): Lipworth BJ. Source: Thorax. 2001 December; 56(12): 980-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758508&dopt=Abstract
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Systemic steroids for the management of obstructive subglottic hemangioma. Author(s): Al-Sebeih K, Manoukian J. Source: The Journal of Otolaryngology. 2000 December; 29(6): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770144&dopt=Abstract
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Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids). Author(s): Sakuma S, Higashi Y, Sato N, Sasakawa T, Sengoku T, Ohkubo Y, Amaya T, Goto T. Source: International Immunopharmacology. 2001 June; 1(6): 1219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407316&dopt=Abstract
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Tacrolimus vs CyA Neoral in combination with MMF and steroids after cadaveric renal transplantation. Author(s): Wang XH, Tang XD, Xu D. Source: Transplantation Proceedings. 2000 November; 32(7): 1702-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119899&dopt=Abstract
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Take steroids to move faster. Author(s): Brooksbank C. Source: Nature Reviews. Molecular Cell Biology. 2001 February; 2(2): 84-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11252961&dopt=Abstract
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Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system. Author(s): Nakayama Y, Sakamoto H, Satoh K, Yamamoto T. Source: Cancer Letters. 2000 December 8; 161(1): 63-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078914&dopt=Abstract
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Tandem mass spectrometry in the study of fatty acids, bile acids, and steroids. Author(s): Griffiths WJ. Source: Mass Spectrometry Reviews. 2003 March-April; 22(2): 81-152. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820273&dopt=Abstract
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Tapering off steroids three months after liver transplantation is not detrimental for hepatitis C virus disease recurrence. Author(s): Belli LS, Alberti AB, Vangeli M, Airoldi A, Pinzello G. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 February; 9(2): 201-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548517&dopt=Abstract
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Targeting inhaled steroids. Author(s): Leach C. Source: Int J Clin Pract Suppl. 1998 September; 96: 23-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10344030&dopt=Abstract
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Th-2 type cytokine receptors in allergic rhinitis and in response to topical steroids. Author(s): Wright ED, Christodoulopoulos P, Small P, Frenkiel S, Hamid Q. Source: The Laryngoscope. 1999 April; 109(4): 551-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10201739&dopt=Abstract
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The addition of sirolimus to cyclosporine and steroids inhibits the anti-equine antibody response in renal transplant recipients treated with antithymocyte globulin. Author(s): Pescovitz MD, Book BK, Henson S, Leapman SB, Milgrom ML, Kimball J, Norman D, Filo RS. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 April; 3(4): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694075&dopt=Abstract
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The adolescents training and learning to avoid steroids program: preventing drug use and promoting health behaviors. Author(s): Goldberg L, MacKinnon DP, Elliot DL, Moe EL, Clarke G, Cheong J. Source: Archives of Pediatrics & Adolescent Medicine. 2000 April; 154(4): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10768668&dopt=Abstract
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The breath of life. Inhaled steroids now seem to be safe for children with moderate asthma. What you should know. Author(s): Gorman C. Source: Time. 2000 October 23; 156(17): 98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184808&dopt=Abstract
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The content of four immunomodulatory steroids and major androgens in human semen. Author(s): Hampl R, Pohanka M, Hill M, Starka L. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 307-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711017&dopt=Abstract
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The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men. Author(s): Taxel P, Kennedy DG, Fall PM, Willard AK, Clive JM, Raisz LG. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 June; 86(6): 2869-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397902&dopt=Abstract
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The effect of postnatal steroids on growth and development. Author(s): Halliday HL. Source: Journal of Perinatal Medicine. 2001; 29(4): 281-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565195&dopt=Abstract
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The effect of steroids on the biophysical profile and Doppler indices of umbilical and middle cerebral arteries in healthy preterm fetuses. Author(s): Deren O, Karaer C, Onderoglu L, Yigit N, Durukan T, Bahado-Singh RO. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 November; 99(1): 72-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604189&dopt=Abstract
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The effect of supraphysiological doses of anabolic androgenic steroids on collagen metabolism. Author(s): Parssinen M, Karila T, Kovanen V, Seppala T. Source: International Journal of Sports Medicine. 2000 August; 21(6): 406-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961515&dopt=Abstract
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The effects of gender and gonadal steroids on the neuroendocrine and temperature response to m-chlorophenylpiperazine in leuprolide-induced hypogonadism in women and men. Author(s): Schmidt PJ, Raju J, Danaceau M, Murphy DL, Berlin RE. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 November; 27(5): 800-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431854&dopt=Abstract
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The effects of sex steroids on spatial performance: a review and an experimental clinical investigation. Author(s): Liben LS, Susman EJ, Finkelstein JW, Chinchilli VM, Kunselman S, Schwab J, Dubas JS, Demers LM, Lookingbill G, Darcangelo MR, Krogh HR, Kulin HE. Source: Developmental Psychology. 2002 March; 38(2): 236-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881759&dopt=Abstract
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The European Consensus Development Conference 2002: Sex Steroids and Cardiovascular Diseases. On the route to combined evidence from OC and HRT/ERT. Author(s): Writing Group for the 3rd European Conference on Sex Steroids and Cardiovascular Diseases. Source: Maturitas. 2003 January 30; 44(1): 69-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568738&dopt=Abstract
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The hiccup reflex arc and persistent hiccups with high-dose anabolic steroids: is the brainstem the steroid-responsive locus? Author(s): Dickerman RD, Jaikumar S. Source: Clinical Neuropharmacology. 2001 January-February; 24(1): 62-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11290884&dopt=Abstract
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The ISOLDE trial. Side effects with inhaled steroids should not be forgotten. Author(s): Lipworth BJ. Source: Bmj (Clinical Research Ed.). 2000 November 25; 321(7272): 1349. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11186442&dopt=Abstract
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The matrix metalloproteinase-1 (MMP-1) expression in the human endometrium is inversely regulated by interleukin-1 alpha and sex steroids. Author(s): Singer CF, Marbaix E, Kokorine I, Lemoine P, Donnez J, Eeckhout Y, Courtoy PJ. Source: Ceska Gynekol. 2000 July; 65(4): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11039223&dopt=Abstract
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The popliteal-artery entrapment syndrome in a patient using anabolic steroids. Author(s): Lepori M, Perren A, Gallino A. Source: The New England Journal of Medicine. 2002 April 18; 346(16): 1254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961162&dopt=Abstract
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The prescription of steroids in the terminal phase. Author(s): Gannon C. Source: Palliative Medicine. 2001 November; 15(6): 522. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403514&dopt=Abstract
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The prevalence of the use of androgenic anabolic steroids by adolescents in a county of Sweden. Author(s): Nilsson S, Baigi A, Marklund B, Fridlund B. Source: European Journal of Public Health. 2001 June; 11(2): 195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420810&dopt=Abstract
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The problem of dose-response and therapeutic ratio of inhaled steroids. Author(s): Lipworth BJ. Source: American Journal of Respiratory and Critical Care Medicine. 2001 June; 163(7): 1758; Author Reply 1759. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401902&dopt=Abstract
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The problem of dose-response and therapeutic ratio of inhaled steroids. Author(s): Edsbacker S. Source: American Journal of Respiratory and Critical Care Medicine. 2001 June; 163(7): 1758-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458876&dopt=Abstract
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The quantification of endogenous steroids in bovine aqueous humour and vitreous humour using isotope dilution GC-NCI-MS. Author(s): Iqbal Z, Midgely JM, Watson DG. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 February; 24(4): 53543. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272309&dopt=Abstract
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The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease. Author(s): Weiner P, Weiner M, Rabner M, Waizman J, Magadle R, Zamir D. Source: Journal of Internal Medicine. 1999 January; 245(1): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10095821&dopt=Abstract
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The risk of cataract among users of inhaled steroids. Author(s): Jick SS, Vasilakis-Scaramozza C, Maier WC. Source: Epidemiology (Cambridge, Mass.). 2001 March; 12(2): 229-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246585&dopt=Abstract
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The role of sex steroids in the regulation of insulin sensitivity and serum lipid concentrations during male puberty: a prospective study with a P450-aromatase inhibitor. Author(s): Wickman S, Saukkonen T, Dunkel L. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 March; 146(3): 339-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888840&dopt=Abstract
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The role of steroids and their effects on phospholipase A2. Author(s): Korovessis PG. Source: Spine. 2000 August 1; 25(15): 2004-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908950&dopt=Abstract
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The role of steroids in acute spinal cord injury: an evidence-based analysis. Author(s): Hurlbert RJ. Source: Spine. 2001 December 15; 26(24 Suppl): S39-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805608&dopt=Abstract
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The use of steroids in the management of inoperable intestinal obstruction in terminal cancer patients: do they remove the obstruction? Author(s): Laval G, Girardier J, Lassauniere JM, Leduc B, Haond C, Schaerer R. Source: Palliative Medicine. 2000 January; 14(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717717&dopt=Abstract
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Thrombotic thrombocytopenic purpura (TTP): initial treatment with plasma exchange plus steroids and immunosuppressive agents for relapsing cases. Author(s): Yang CW, Chen YC, Dunn P, Chang MY, Fang JT, Huang CC. Source: Renal Failure. 2003 January; 25(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617330&dopt=Abstract
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Ticlopidine-induced thrombotic thrombocytopenic purpura: two case reports treated with plasma exchange plus steroids. Author(s): Yang CW, Chen YC, Dunn P, Chang MY, Fang JT, Huang CC. Source: Renal Failure. 2001 November; 23(6): 851-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777325&dopt=Abstract
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Tonsillectomy and postoperative vomiting: Do steroids really work? Author(s): Shott SR. Source: Archives of Otolaryngology--Head & Neck Surgery. 2001 August; 127(8): 100910. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493217&dopt=Abstract
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Topical medications: a focus on antifungals and topical steroids. Author(s): Webster GF. Source: Clinical Cornerstone. 2001; 4(1): 33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739320&dopt=Abstract
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Topical steroids under wet-wrap dressings in atopic dermatitis--a vehicle-controlled trial. Author(s): Schnopp C, Holtmann C, Stock S, Remling R, Folster-Holst R, Ring J, Abeck D. Source: Dermatology (Basel, Switzerland). 2002; 204(1): 56-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834851&dopt=Abstract
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Topical steroids--a new approach after 50 years. Author(s): Wozniacka A, Sysa-Jedrzejowska A. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 May-June; 7(3): 539-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386039&dopt=Abstract
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Tracheal obstruction after insertion of a self-expanding metal esophageal stent: successful management with an endotracheal tube, steroids, and radiotherapy. Author(s): Alvares JF, Devarbhavi H, Shetty S, Pais A, Sharma S. Source: Endoscopy. 2002 July; 34(7): 592. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170419&dopt=Abstract
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Transplantation without steroids. Author(s): Alexander JW, Stanley LL, Ofstedal TL, First MR, Cardi MA, Safdar S, Mendoza NC, Munda R, Fidler JP, Buell JF, Hanaway MJ, Woodle ES. Source: Transplantation Proceedings. 2002 September; 34(6): 2076-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270319&dopt=Abstract
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Transtympanic steroids for treatment of sudden hearing loss. Author(s): Gianoli GJ, Li JC. Source: Otolaryngology and Head and Neck Surgery. 2001 September; 125(3): 142-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555744&dopt=Abstract
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Traumatic enucleation with chiasmal damage: magnetic resonance image findings and response to steroids. Author(s): Parmar B, Edmunds B, Plant G. Source: The British Journal of Ophthalmology. 2002 November; 86(11): 1317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386102&dopt=Abstract
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Treatment of allergic rhinitis with intranasal steroids and their effects on the lower airway. Author(s): Schenkel EJ, Berger WE. Source: Pediatric Annals. 2000 July; 29(7): 422-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10911631&dopt=Abstract
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Treatment of bullous pemphigoid by low-dose methotrexate associated with shortterm potent topical steroids: an open prospective study of 18 cases. Author(s): Dereure O, Bessis D, Guillot B, Guilhou JJ. Source: Archives of Dermatology. 2002 September; 138(9): 1255-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225001&dopt=Abstract
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Treatment of focal glomerulosclerosis with pulse steroids and oral cyclophosphamide. Author(s): Hari P, Bagga A, Jindal N, Srivastava RN. Source: Pediatric Nephrology (Berlin, Germany). 2001 November; 16(11): 901-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685598&dopt=Abstract
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Treatment of giant cell granuloma of the maxilla with intralesional injection of steroids. Author(s): Khafif A, Krempl G, Medina JE. Source: Head & Neck. 2000 December; 22(8): 822-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084644&dopt=Abstract
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Treatment of immune recovery vitritis with local steroids. Author(s): Henderson HW, Mitchell SM. Source: The British Journal of Ophthalmology. 1999 May; 83(5): 540-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10216051&dopt=Abstract
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Treatment of ocular myasthenia: steroids only when compelled. Author(s): Kaminski HJ, Daroff RB. Source: Archives of Neurology. 2000 May; 57(5): 752-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815146&dopt=Abstract
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Treatment of phimosis with topical steroids in 194 children. Author(s): Ashfield JE, Nickel KR, Siemens DR, MacNeily AE, Nickel JC. Source: The Journal of Urology. 2003 March; 169(3): 1106-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576863&dopt=Abstract
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Treatment of Sjogren syndrome myelopathy with azathioprine and steroids. Author(s): Hawley RJ, Hendricks WT. Source: Archives of Neurology. 2002 May; 59(5): 875; Author Reply 876. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020280&dopt=Abstract
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Treatment of sudden sensorineural hearing loss with systemic steroids and valacyclovir. Author(s): Tucci DL, Farmer JC Jr, Kitch RD, Witsell DL. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 May; 23(3): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981385&dopt=Abstract
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Treatment of ulcerative endobronchial tuberculosis and bronchial stenosis with aerosolized streptomycin and steroids. Author(s): Rikimaru T, Koga T, Sueyasu Y, Ide S, Kinosita M, Sugihara E, Oizumi K. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2001 August; 5(8): 769-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495269&dopt=Abstract
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Trial of steroids for treating head injury begins. Author(s): Kmietowicz Z. Source: Bmj (Clinical Research Ed.). 1999 May 29; 318(7196): 1441. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10346763&dopt=Abstract
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Troglitazone-associated hepatotoxicity treated successfully with steroids. Author(s): Prendergast KA, Berg CL, Wisniewski R. Source: Annals of Internal Medicine. 2000 November 7; 133(9): 751. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074925&dopt=Abstract
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Tumefactive fibroinflammatory lesion of the head and neck treated with steroids: a case report. Author(s): Hostalet F, Hellin D, Ruiz JA. Source: Eur Arch Otorhinolaryngol. 2003 April;260(4):229-31. Epub 2002 November 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709810&dopt=Abstract
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Two neuroactive steroids in midpregnancy as measured in maternal and fetal sera and in amniotic fluid. Author(s): Bicikova M, Klak J, Hill M, Zizka Z, Hampl R, Calda P. Source: Steroids. 2002 April; 67(5): 399-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958797&dopt=Abstract
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Ultrasonographic guidance for injections of local steroids in the native hip. Author(s): Carson BW, Wong A. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1999 February; 18(2): 159-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10206810&dopt=Abstract
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Urinary profile of endogenous steroids in postmenopausal women with stress urinary incontinence. Author(s): Jung BH, Bai SW, Chung BC. Source: J Reprod Med. 2001 November; 46(11): 969-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762153&dopt=Abstract
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Urinary steroids at time of surgery in postmenopausal women with breast cancer. Author(s): Juricskay S, Szabo I, Kett K. Source: Breast Cancer Research and Treatment. 1997 May; 44(1): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9164681&dopt=Abstract
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Urinary steroids in men with male-pattern alopecia. Author(s): Poor V, Juricskay S, Telegdy E. Source: Journal of Biochemical and Biophysical Methods. 2002 October-November; 53(13): 123-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406594&dopt=Abstract
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Urinary steroids in women with androgenic alopecia. Author(s): Juricskay S, Telegdy E. Source: Clinical Biochemistry. 2000 March; 33(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751586&dopt=Abstract
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Urticaria pigmentosa--response to topical steroids. Author(s): Higgins EM, Humphreys S, Duvivier AW. Source: Clinical and Experimental Dermatology. 1994 September; 19(5): 438-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7955511&dopt=Abstract
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Use of anabolic steroids and associated health risks among gay men attending London gyms. Author(s): Bolding G, Sherr L, Elford J. Source: Addiction (Abingdon, England). 2002 February; 97(2): 195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860391&dopt=Abstract
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Use of anabolic steroids has been reported by 9% of men attending gymnasiums. Author(s): Korkia P. Source: Bmj (Clinical Research Ed.). 1996 October 19; 313(7063): 1009. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8892444&dopt=Abstract
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Use of anabolic-androgenic steroids in adolescence: winning, looking good or being bad? Author(s): Wichstrom L, Pedersen W. Source: J Stud Alcohol. 2001 January; 62(1): 5-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271964&dopt=Abstract
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Use of basiliximab in conjunction with either Neora/MMF/steroids or Prograf/MMF/steroids in simultaneous pancreas-kidney transplantation. Author(s): Boggi U, Vistoli F, Coppelli A, Marchetti P, Rizzo G, Mosca F. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3201-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750373&dopt=Abstract
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Use of epidural steroids after discectomy may predispose to infection. Author(s): Lowell TD, Errico TJ, Eskenazi MS. Source: Spine. 2000 February 15; 25(4): 516-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10707400&dopt=Abstract
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Use of nasal steroids in managing allergic rhinitis. Author(s): LaForce C. Source: The Journal of Allergy and Clinical Immunology. 1999 March; 103(3 Pt 2): S38894. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10069899&dopt=Abstract
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Use of particle-loaded membranes to extract steroids for high-performance liquid chromatographic analyses improved analyte stability and detection. Author(s): Lensmeyer GL, Onsager C, Carlson IH, Wiebe DA. Source: J Chromatogr A. 1995 February 3; 691(1-2): 239-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7894649&dopt=Abstract
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Use of plasma exchange, steroids, and anticoagulation in a patient with multiple arterial thromboses and IgM anticardiolipin antibodies. Author(s): Sachais BS, Thompson JE, Strobl FJ. Source: Journal of Clinical Apheresis. 2002; 17(3): 138-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378550&dopt=Abstract
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Use of postoperative steroids to reduce pain and inflammation. Author(s): Fleischli JW, Adams WR. Source: The Journal of Foot and Ankle Surgery : Official Publication of the American College of Foot and Ankle Surgeons. 1999 May-June; 38(3): 232-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10384365&dopt=Abstract
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Use of spacer devices with inhaled steroids. Author(s): Craig T. Source: Archives of Internal Medicine. 1995 March 13; 155(5): 547-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7864715&dopt=Abstract
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Use of steroids after strabismus surgery. Author(s): Chipont E, Garcia-Hermosa P. Source: Journal of Pediatric Ophthalmology and Strabismus. 2000 May-June; 37(3): 1768. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10845421&dopt=Abstract
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Use of steroids for acute spinal cord injury must be reassessed. Author(s): Short D. Source: Bmj (Clinical Research Ed.). 2000 November 11; 321(7270): 1224. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11073527&dopt=Abstract
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Use of steroids in renal transplantation. Author(s): Ponticelli C, Tarantino A, Montagnino G, Vegeto A. Source: Transplantation Proceedings. 1999 September; 31(6): 2210-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500548&dopt=Abstract
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Use of supplemental steroids in patients having orthopaedic operations. Author(s): Friedman RJ, Schiff CF, Bromberg JS. Source: The Journal of Bone and Joint Surgery. American Volume. 1995 December; 77(12): 1801-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8550646&dopt=Abstract
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Vaccinations and steroids in MS: effects on disease progression and mood. Author(s): Kollegger H, Schmied M, Zebenholzer K, Zeiler K, Hittmair K, Mallek R. Source: Acta Neurologica Scandinavica. 1999 July; 100(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10416515&dopt=Abstract
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Value and safety of steroids in treating ear disease. Author(s): Rutka J, Deitmer T, Dohar J. Source: Ear, Nose, & Throat Journal. 2003 August; 82(8 Suppl 2): 5-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974050&dopt=Abstract
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Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. Author(s): McLaren J, Prentice A, Charnock-Jones DS, Millican SA, Muller KH, Sharkey AM, Smith SK. Source: The Journal of Clinical Investigation. 1996 July 15; 98(2): 482-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8755660&dopt=Abstract
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Visual hallucinations induced by intraarticular injection of steroids. Author(s): Daragon A, Vittecoq O, Le Loet X. Source: The Journal of Rheumatology. 1997 February; 24(2): 411. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9035012&dopt=Abstract
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Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis. Author(s): Shah GK, Stein JD, Sharma S, Sivalingam A, Benson WE, Regillo CD, Brown GC, Tasman W. Source: Ophthalmology. 2000 March; 107(3): 486-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711885&dopt=Abstract
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Vitamin D analogs modulate the action of gonadal steroids in human vascular cells in vitro. Author(s): Somjen D, Kohen F, Amir-Zaltsman Y, Knoll E, Stern N. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2000 April; 13(4 Pt 1): 396-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821342&dopt=Abstract
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Weakness of respiratory and skeletal muscles after a short course of steroids in patients with acute lung rejection. Author(s): Nava S, Fracchia C, Callegari G, Ambrosino N, Barbarito N, Felicetti G. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 August; 20(2): 497-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212986&dopt=Abstract
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Weight training. A potential confounding factor in examining the psychological and behavioural effects of anabolic-androgenic steroids. Author(s): Bahrke MS, Yesalis CE 3rd. Source: Sports Medicine (Auckland, N.Z.). 1994 November; 18(5): 309-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871292&dopt=Abstract
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What's new in contact dermatitis: allergy to topical steroids in Israeli patients with contact dermatitis. Author(s): Ingber A. Source: Isr Med Assoc J. 2002 November; 4(11 Suppl): 867. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455163&dopt=Abstract
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Which steroids for the treatment of skin disorders on the face? Author(s): Dubertret L. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 March; 16(2): 121. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046811&dopt=Abstract
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Why do steroids increase blood pressure in preterm infants? Author(s): Seri I, Evans JR. Source: The Journal of Pediatrics. 2000 March; 136(3): 420-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10700707&dopt=Abstract
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Widespread application of topical steroids to decrease sore throat, hoarseness, and cough after tracheal intubation. Author(s): Ayoub CM, Ghobashy A, Koch ME, McGrimley L, Pascale V, Qadir S, Ferneini EM, Silverman DG. Source: Anesthesia and Analgesia. 1998 September; 87(3): 714-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9728859&dopt=Abstract
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Widespread cutaneous lesions due to Sporothrix schenckii in a patient under a longterm steroids therapy. Author(s): Severo LC, Festugato M, Bernardi C, Londero AT. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 1999 January-February; 41(1): 59-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436671&dopt=Abstract
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Willingness of patients to perform self-management of asthma and the role of inhaled steroids. Author(s): Thoonen BP, Schermer TR, Akkermans RP, den Otter JJ, Grol R, van Schayck OC. Source: Scandinavian Journal of Primary Health Care. 2002 March; 20(1): 60-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086288&dopt=Abstract
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Withdrawal from anabolic steroids. Author(s): Brower KJ. Source: Curr Ther Endocrinol Metab. 1997; 6: 338-43. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9174765&dopt=Abstract
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Withdrawal of steroids from a cyclosporine-based regimen: pro. Author(s): Ponticelli C. Source: Transplantation Proceedings. 1998 August; 30(5): 1782-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9723281&dopt=Abstract
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Withdrawal of steroids from triple-drug therapy in kidney transplant patients. Author(s): Matl I, Lacha J, Lodererova A, Simova M, Teplan V, Lanska V, Vitko S. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 July; 15(7): 1041-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10862645&dopt=Abstract
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Withdrawal or reduction of steroids based on pharmacodynamics assessed by antilymphocyte action after renal transplantation. Author(s): Kozaki K, Takeuchi H, Hirano T, Oka K, Sakurai E, Uchiyama M, Matsuno N, Yoshida M, Kozaki M. Source: Transplantation Proceedings. 1996 June; 28(3): 1300-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8658668&dopt=Abstract
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CHAPTER 2. NUTRITION AND STEROIDS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and steroids.
Finding Nutrition Studies on Steroids The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “steroids” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on steroids: •
Plants as a source of vitamin D3 metabolites. Source: Boland, R.L. Nutrition-reviews (USA). (January 1986). volume 44(1) page 1-8. vitamin d metabolism plants calcium mineral metabolism toxicology steroids bone formation experiments 0029-6643 Summary: vitamine d metabolisme plante calcium metabolisme des mineraux toxicologie steroide formation des os experimentation
The following information is typical of that found when using the “Full IBIDS Database” to search for “steroids” (or a synonym): •
A novel steroid from Tylophora atrofolliculata Metc. Author(s): Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Source: Huang, X S Yu, S S Liang, X T Li, N J-Asian-Nat-Prod-Res. 2002 September; 4(3): 197-200 1028-6020
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Biotransformations of putative phytoecdysteroid biosynthetic precursors in tissue cultures of Polypodium vulgare. Author(s): Department of Biological Organic Chemistry, IIQAB-CSIC, Barcelona, Spain. Source: Reixach, N Lafont, R Camps, F Casas, J Eur-J-Biochem. 1999 December; 266(2): 608-15 0014-2956
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Brassinosteroids. Plant counterparts to animal steroid hormones? Author(s): Department of Horticultural Science, North Carolina State University, Raleigh, North Carolina 27695, USA. Source: Clouse, S D Vitam-Horm. 2002; 65: 195-223 0083-6729
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Cardiotonic steroids: potential endogenous sodium pump ligands with diverse function. Author(s): Institute of Molecular Medicine, University of Texas, Houston, Texas 77030, USA. Source: Dmitrieva, R I Doris, P A Exp-Biol-Med-(Maywood). 2002 September; 227(8): 561-9 1535-3702
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Controversies in the use of postnatal steroids. Author(s): Department of Pediatrics, University of Texas Houston Medical School, 77030, USA.
[email protected] Source: Kennedy, K A Semin-Perinatol. 2001 December; 25(6): 397-405 0146-0005
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Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes. Author(s): Division of Pharmacy, Chiba University Hospital, Chuo-ku, Chiba, Japan. Source: Nakamura, H Nakasa, H Ishii, I Ariyoshi, N Igarashi, T Ohmori, S Kitada, M Drug-Metab-Dispos. 2002 May; 30(5): 534-40 0090-9556
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Effects of long-term inhaled steroid use on bone mineral density in asthma patients. Author(s): Department of the Chest Diseases, University of Firat-Turkey, Medical School, Elazig.
[email protected] Source: Tug, T Kamanli, A Tug, E J-Investig-Allergol-Clin-Immunol. 2001; 11(4): 300-2 1018-9068
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Four novel withanolide-type steroids from the leaves of Solanum cilistum. Author(s): Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
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Source: Zhu, X H Ando, J Takagi, M Ikeda, T Yoshimitsu, A Nohara, T Chem-PharmBull-(Tokyo). 2001 November; 49(11): 1440-3 0009-2363 •
GnRH and steroids in cancer. Author(s): Dept. of Structures, Functions and Biological Technologies, School of Veterinary Medicine University of Naples Federico II Naples Italy.
[email protected] Source: Florio, Salvatore Pagnini, Ugo Crispino, Antonio Pacilio, Carmen Crispino, Luca Giordano, Antonio Front-Biosci. 2002 June 1; 7: d1590-608 1093-4715
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HET-CAM bioassay as in vitro alternative to the croton oil test for investigating steroidal and non-steroidal compounds. Author(s): Institute of Pharmacognosy, University of Graz, A-Graz, Trieste.
[email protected] Source: Brantner, A H Quehenberger, F Chakraborty, A Polligger, J Sosa, S Della Loggia, R ALTEX. 2002; 19(2): 51-6 0946-7785
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Isolation of a new member of the ecdysteroid glycoside family: 2-deoxy-20hydroxyecdysone 22-O-beta-D-glucopyranoside. Author(s): Department of Pharmacognosy, University of Szeged, Hungary.
[email protected] Source: Bathori, M Pongracz, Z Toth, G Simon, A Kandra, L Kele, Z Ohmacht, R JChromatogr-Sci. 2002 August; 40(7): 409-15 0021-9665
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Melanocortins are comparable to corticosteroids as inhibitors of traumatic ocular inflammation in rabbits. Author(s):
[email protected] Source: Naveh, N Marshall, J Graefes-Arch-Clin-Exp-Ophthalmol. 2001 November; 239(11): 840-4 0721-832X
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Metabolic effects of infection and postnatal steroids. Author(s): Department of Pediatrics, University of Minnesota, MMC 185, Minneapolis, MN 55455, USA.
[email protected] Source: Schwarzenberg, S J Kovacs, A Clin-Perinatol. 2002 June; 29(2): 295-312 0095-5108
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Neurosteroids and infantile spasms: the deoxycorticosterone hypothesis. Author(s): Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Source: Rogawski, M A Reddy, D S Int-Rev-Neurobiol. 2002; 49: 199-219 0074-7742
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New biologically active marine sesquiterpenoid and steroid from the okinawan sponge of the genus Axinyssa. Author(s): School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. Source: Iwashima, M Terada, I Iguchi, K Yamori, T Chem-Pharm-Bull-(Tokyo). 2002 September; 50(9): 1286-9 0009-2363
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New steroidal alkaloids from Fritillaria imperialis and their cholinesterase inhibiting activities. Author(s): H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan. Source: Atta Ur Rahman Akhtar, M N Choudhary, M I Tsuda, Y Sener, B Khalid, A Parvez, M Chem-Pharm-Bull-(Tokyo). 2002 August; 50(8): 1013-6 0009-2363
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Oxytocin regulates neurosteroid modulation of GABA(A) receptors in supraoptic nucleus around parturition. Author(s): Department of Experimental Neurophysiology, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
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Source: Koksma, J J van Kesteren, R E Rosahl, T W Zwart, R Smit, A B Luddens, H Brussaard, A B J-Neurosci. 2003 February 1; 23(3): 788-97 1529-2401 •
Patient preferences and satisfaction with prescribed nasal steroids for allergic rhinitis. Author(s): Institute for Asthma and Allergy, 1160 Veirs Mill Road, Suite 414, Wheaton, MD 20902, USA. Source: Kaliner, M A Allergy-Asthma-Proc. 2001 Nov-December; 22(6 Suppl 1): S11-5 1088-5412
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Physician prescribing practices: the role of patient preference in the selection of nasal steroids. Author(s): Institute for Asthma and Allergy, 11160 Veirs Mill Road, Suite 114, Wheaton, MD 20902, USA. Source: Kaliner, M A Allergy-Asthma-Proc. 2001 Nov-December; 22(6 Suppl 1): S17-22 1088-5412
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Phytoestrogens as modulators of steroid action in target cells. Author(s): U361 INSERM, Universite Paris V, Pavillon Baudelocque, Port Royal Cochin, Paris, France. Source: Benassayag, C Perrot Applanat, M Ferre, F J-Chromatogr-B-Analyt-TechnolBiomed-Life-Sci. 2002 September 25; 777(1-2): 233-48 1570-0232
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Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women. Author(s): Department of Orthopaedics, Karolinska Institute and Danderyd Hospital, Sweden. Source: Hedstrom, M Sjoberg, K Brosjo, E Astrom, K Sjoberg, H Dalen, N J-Bone-JointSurg-Br. 2002 May; 84(4): 497-503 0301-620X
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Possible role of corticosteroids in nervous system plasticity: improvement in amblyopia after optic neuritis in the fellow eye treated with steroids. Author(s): Division of Clinical Neurology, University Hospital, Queen's Medical Centre, Nottingham, UK.
[email protected] Source: Constantinescu C, S Gottlob, I Neurorehabil-Neural-Repair. 2001; 15(3): 223-7
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Pro/con clinical debate: are steroids useful in the management of patients with septic shock? Author(s): Resident, Department of Medicine, University of Toronto, Canada. Source: Ritacca, Frank V Simone, Carmine Wax, Randy Craig, Katherine G Walley, Keith R Crit-Care. 2002 April; 6(2): 113-6 1364-8535
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Pulsatile release of sex steroids? A hypothesis to explain anomalies in hormonal therapy. Author(s): Sydney Menopause Centre, Royal Hospital for Women, Randwick, New South Wales, Australia. Source: Wren, B G Climacteric. 2000 March; 3(1): 68-70 1369-7137
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Rapid discontinuation of steroids in living donor kidney transplantation: a pilot study. Author(s): Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
[email protected] Source: Matas, A J Ramcharan, T Paraskevas, S Gillingham, K J Dunn, D L Gruessner, R W HuMarch, A Kandaswamy, R Najarian, J S Payne, W D Sutherland, D E Am-JTransplant. 2001 September; 1(3): 278-83 1600-6135
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Rapid transbilayer movement of spin-labeled steroids in human erythrocytes and in liposomes. Author(s): Humboldt-Universitat zu Berlin, Mathematisch-Naturwissenschaftliche Fakultat I, Institut fur Biologie/Biophysik, D-10115 Berlin, Germany.
[email protected] Source: Muller, Peter Herrmann, Andreas Biophys-J. 2002 March; 82(3): 1418-28 00063495
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Regulation of the 24h body temperature rhythm of women in luteal phase: role of gonadal steroids and prostaglandins. Author(s): Institute of Obstetrics and Gynecology, University of Modena, Italy.
[email protected] Source: Cagnacci, A Arangino, S Tuveri, F Paoletti, A M Volpe, A Chronobiol-Int. 2002 July; 19(4): 721-30 0742-0528
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Renal effects of antenatally or postnatally administered steroids. Author(s): Division of Neonatology, Brescia Hospital, Italy. Source: Cattarelli, D Chirico, G Simeoni, U Pediatr-Med-Chir. 2002 Mar-April; 24(2): 15762 0391-5387
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Sex steroids and the construction and conservation of the adult skeleton. Author(s): Division of Endocrinology and Metabolism, Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
[email protected] Source: Riggs, B L Khosla, S Melton, L J 3rd Endocr-Revolume 2002 June; 23(3): 279-302 0163-769X
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Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca. Author(s): GBF-Gesellschaft fur Biotechnologische Forschung, Abteilung NBI/MX, Mascheroder Weg 1, 38124 Braunschweig, Germany. Source: Bode, H B Zeggel, B Silakowski, B Wenzel, S C Reichenbach, H Muller, R MolMicrobiol. 2003 January; 47(2): 471-81 0950-382X
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Steroids for Crohn's disease--an appreciation and a vote of confidence. Author(s): Section of Gastroenterology, Lenox Hill Hospital, New York University School of Medicine, New York 10021, USA. Source: Korelitz, Burton I Inflamm-Bowel-Dis. 2002 May; 8(3): 219-22 1078-0998
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Steroids in sepsis--more effective than activated protein C? Author(s): St. George's Hospital, London, UK. Source: Bradley, C Intensive-Crit-Care-Nurs. 2001 August; 17(4): 242-4 0964-3397
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Steroids masquerading as natural herbs: a case for regulatory control. Author(s):
[email protected] Source: Reti, S N-Z-Med-J. 2002 August 9; 115(1159): U125 1175-8716
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Strain differences in sigma(1) receptor-mediated behaviours are related to neurosteroid levels. Author(s): Behavioural Neuropharmacology group, INSERM U.336, Institut de Biologie, 4, blvd Henri IV, 34060 Montpellier, France. Source: Phan, Van Ly Urani, Alexandre Romieu, Pascal Maurice, Tangui Eur-J-Neurosci. 2002 May; 15(9): 1523-34 0953-816X
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The effects of sex steroids on spatial performance: a review and an experimental clinical investigation. Author(s): Department of Psychology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
[email protected] Source: Liben, Lynn S Susman, Elizabeth J Finkelstein, Jordan W Chinchilli, Vernon M Kunselman, Susan Schwab, Jacqueline Dubas, Judith Semon Demers, Laurence M Lookingbill, Georgia Darcangelo, M Rose Krogh, Holleen R Kulin, Howard E DevPsychol. 2002 March; 38(2): 236-53 0012-1649
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Treatment of sudden sensorineural hearing loss with systemic steroids and valacyclovir. Author(s): Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
[email protected] Source: Tucci, Debara L Farmer, Joseph C Jr Kitch, Russell D Witsell, David L OtolNeurotol. 2002 May; 23(3): 301-8 1531-7129
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to steroids; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Ascorbic Acid Alternative names: Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Pantothenic Acid Source: Healthnotes, Inc. www.healthnotes.com Vitamin A Source: Healthnotes, Inc. www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: Healthnotes, Inc. www.healthnotes.com Vitamin C (Ascorbic Acid) Alternative names: Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Healthnotes, Inc. www.healthnotes.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin K Source: Healthnotes, Inc. www.healthnotes.com
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Minerals Betaine Hydrochloride Source: Healthnotes, Inc. www.healthnotes.com Biotin Source: Healthnotes, Inc. www.healthnotes.com Boron Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Chondroitin Source: Prima Communications, Inc.www.personalhealthzone.com Chondroitin Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10017,00.html Chromium Source: Healthnotes, Inc. www.healthnotes.com Copper Source: Integrative Medicine Communications; www.drkoop.com Creatine Source: Integrative Medicine Communications; www.drkoop.com Creatine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10020,00.html Magnesium Source: Healthnotes, Inc. www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com
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Naproxen/Naproxen Sodium Source: Healthnotes, Inc. www.healthnotes.com Phosphocreatine Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Healthnotes, Inc. www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Prima Communications, Inc.www.personalhealthzone.com Potassium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10086,00.html Selenium Source: Healthnotes, Inc. www.healthnotes.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Stinging Nettle Alternative names: Urtica dioica, Urtica urens, Nettle Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc. www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com •
Food and Diet Diabetes Source: Healthnotes, Inc. www.healthnotes.com High Cholesterol Source: Healthnotes, Inc. www.healthnotes.com Low-Purine Diet Source: Healthnotes, Inc. www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com
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Omega-3 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Soy Source: Healthnotes, Inc. www.healthnotes.com Vegetarian Diet Source: Healthnotes, Inc. www.healthnotes.com Wound Healing Source: Healthnotes, Inc. www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND STEROIDS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to steroids. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “steroids” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Facts About Dietary Supplements for the Warfighter: Herbs and Botanicals, Amino Acids, Steroids, Vitamins and Minerals Source: Abderdeen Proving Ground, MD: U.S. Army Center for Health Promotion and Preventive Medicine. 2003. [2 p.]. Contact: Available from U.S. Army Center for Health Promotion and Preventive Medicine. 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5403. (800) 2229698. PRICE: Free. Summary: This brochure, produced for the U.S. Army Center for Health Promotion and Prevention Medicine, provides information about dietary supplements, specifically herbs and botanicals, amino acids, steroids, and vitamins and minerals. It discusses what these dietary supplements are, how supplements are regulated, and the possible side effects of certain dietary supplements. The brochure offers guidelines for using
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dietary supplements, as well as several sources for reliable information on dietary supplements.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to steroids and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “steroids” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to steroids: •
12alpha-hydroxystigmast-4-en-3-one: a new bioactive steroid from Toona ciliata (Meliaceae). Author(s): Chowdhury R, Rashid RB, Sohrab MH, Hasan CM. Source: Pharmazie. 2003 April; 58(4): 272-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749412&dopt=Abstract
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9alpha,20-Dihydroxyecdysone, a new natural ecdysteroid from Silene italica ssp. nemoralis. Author(s): Pongracz Z, Bathori M, Toth G, Simon A, Mak M, Mathe I. Source: Journal of Natural Products. 2003 March; 66(3): 450-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662114&dopt=Abstract
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A new bioactive steroidal saponin from Sansevieria cylindrica. Author(s): Da Silva Antunes A, Da Silva BP, Parente JP, Valente AP. Source: Phytotherapy Research : Ptr. 2003 February; 17(2): 179-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601684&dopt=Abstract
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Anxiogenic effects of neurosteroid exposure: sex differences and altered GABAA receptor pharmacology in adult rats. Author(s): Gulinello M, Smith SS. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 May; 305(2): 541-8. Epub 2003 February 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606703&dopt=Abstract
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BMP-6-induced osteogenic differentiation of mesenchymal cell lines is not modulated by sex steroids and resveratrol. Author(s): Gruber R, Graninger W, Bobacz K, Watzek G, Erlacher L. Source: Cytokine. 2003 August 21-September 7; 23(4-5): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967649&dopt=Abstract
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Canalization of development and ecdysteroid timing during the last instar in lubber grasshoppers. Author(s): Hatle JD, Miller WA, Borst DW. Source: Journal of Insect Physiology. 2003 January; 49(1): 73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770018&dopt=Abstract
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Cardioactive steroid poisoning from an herbal cleansing preparation. Author(s): Barrueto F Jr, Jortani SA, Valdes R Jr, Hoffman RS, Nelson LS. Source: Annals of Emergency Medicine. 2003 March; 41(3): 396-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605208&dopt=Abstract
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Corticosteroids, eosinophils and bronchial epithelial cells: new insights into the resolution of inflammation in asthma. Author(s): Walsh GM, Sexton DW, Blaylock MG. Source: The Journal of Endocrinology. 2003 July; 178(1): 37-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844334&dopt=Abstract
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Effects of anti-ecdysteroid quaternary derivatives of azole analogues of metyrapone on the post-embryonic development of the red cotton bug (Dysdercus cingulatus F). Author(s): Belai I, Fekete G. Source: Pest Management Science. 2003 April; 59(4): 401-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701700&dopt=Abstract
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Effects of corticosteroid and electroacupuncture on experimental spinal cord injury in dogs. Author(s): Yang JW, Jeong SM, Seo KM, Nam TC. Source: J Vet Sci. 2003 April; 4(1): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819372&dopt=Abstract
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Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Author(s): Gholap S, Kar A. Source: Pharmazie. 2003 June; 58(6): 413-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857006&dopt=Abstract
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Glucose and ecdysteroid increase apyrene sperm production in in vitro cultivation of spermatocysts of Bombyx mori. Author(s): Kawamura N, Sahara K, Fugo H. Source: Journal of Insect Physiology. 2003 January; 49(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770013&dopt=Abstract
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Inhibition of ovarian steroidogenesis by cyclic GMP in a fly. Author(s): Maniere G, Vanhems E, Gautron F, Delbecque JP.
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Source: The Journal of Endocrinology. 2003 April; 177(1): 35-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697035&dopt=Abstract •
Insecticidal activity of a nonsteroidal moulting hormone agonist on mosquito larvae and effects on ecdysteroid amounts. Author(s): Boudjelida H, Bouaziz A, Smagghe G, Soltani N. Source: Meded Rijksuniv Gent Fak Landbouwkd Toegep Biol Wet. 2002; 67(3): 657-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696434&dopt=Abstract
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Ovary development and polydnavirus morphogenesis in the parasitic wasp Chelonus inanitus. I. Ovary morphogenesis, amplification of viral DNA and ecdysteroid titres. Author(s): Marti D, Grossniklaus-Burgin C, Wyder S, Wyler T, Lanzrein B. Source: The Journal of General Virology. 2003 May; 84(Pt 5): 1141-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692279&dopt=Abstract
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Purification, kinetic characterization, and molecular cloning of a novel enzyme ecdysteroid-phosphate phosphatase. Author(s): Yamada R, Sonobe H. Source: The Journal of Biological Chemistry. 2003 July 18; 278(29): 26365-73. Epub 2003 April 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721294&dopt=Abstract
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RU49953: a non-hormonal steroid derivative that potently inhibits P-glycoprotein and reverts cellular multidrug resistance. Author(s): Perez-Victorias FJ, Conseil G, Munoz-Martinez F, Perez-Victoria JM, Dayan G, Marsaud V, Castanys S, Gamarro F, Renoir JM, Di Pietro A. Source: Cellular and Molecular Life Sciences : Cmls. 2003 March; 60(3): 526-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737312&dopt=Abstract
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Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Author(s): Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, Kao WY, Uen WC, Hsu CH, Tien HF, Chao TY, Chen LT, Whang-Peng J; Lymphoma Committee of Taiwan Cooperative Oncology Group. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1320-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774010&dopt=Abstract
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Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity. Author(s): Tinley TL, Randall-Hlubek DA, Leal RM, Jackson EM, Cessac JW, Quada JC Jr, Hemscheidt TK, Mooberry SL. Source: Cancer Research. 2003 June 15; 63(12): 3211-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810650&dopt=Abstract
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The cytotoxicity of methyl protoneogracillin (NSC-698793) and gracillin (NSC698787), two steroidal saponins from the rhizomes of Dioscorea collettii var. hypoglauca, against human cancer cells in vitro. Author(s): Hu K, Yao X. Source: Phytotherapy Research : Ptr. 2003 June; 17(6): 620-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820229&dopt=Abstract
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The dose related effect of steroids on blast reduction rate and event free survival in children with acute lymphoblastic leukemia. Author(s): Yetgin S, Cetin M. Source: Leukemia & Lymphoma. 2003 March; 44(3): 489-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688320&dopt=Abstract
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The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Author(s): Baker KD, Shewchuk LM, Kozlova T, Makishima M, Hassell A, Wisely B, Caravella JA, Lambert MH, Reinking JL, Krause H, Thummel CS, Willson TM, Mangelsdorf DJ. Source: Cell. 2003 June 13; 113(6): 731-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809604&dopt=Abstract
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Transcriptional suppression of the adrenal cortical peripheral-type benzodiazepine receptor gene and inhibition of steroid synthesis by ginkgolide B. Author(s): Amri H, Drieu K, Papadopoulos V. Source: Biochemical Pharmacology. 2003 March 1; 65(5): 717-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628485&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to steroids; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Acne Source: Integrative Medicine Communications; www.drkoop.com Allergic Reaction, Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Allergic Reaction, Angioedema Source: Integrative Medicine Communications; www.drkoop.com Allergic Rhinitis Source: Integrative Medicine Communications; www.drkoop.com Allergies Alternative names: Hay Fever Source: Prima Communications, Inc.www.personalhealthzone.com Allergies and Sensitivities Source: Healthnotes, Inc. www.healthnotes.com Alopecia Source: Integrative Medicine Communications; www.drkoop.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Amenorrhea Source: Healthnotes, Inc. www.healthnotes.com Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Anemia Source: Integrative Medicine Communications; www.drkoop.com Angioedema Source: Integrative Medicine Communications; www.drkoop.com Arthritis, Rheumatoid Source: Integrative Medicine Communications; www.drkoop.com
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Asthma Source: Healthnotes, Inc. www.healthnotes.com Asthma Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Prima Communications, Inc.www.personalhealthzone.com Bell's Palsy Source: Healthnotes, Inc. www.healthnotes.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Brain Cancer Source: Integrative Medicine Communications; www.drkoop.com Brain Inflammation, Meningitis Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc. www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Bronchitis Source: Integrative Medicine Communications; www.drkoop.com Bursitis Source: Healthnotes, Inc. www.healthnotes.com Bursitis Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Canker Sores Source: Healthnotes, Inc. www.healthnotes.com Carpal Tunnel Syndrome Source: Healthnotes, Inc. www.healthnotes.com Carpal Tunnel Syndrome Source: Integrative Medicine Communications; www.drkoop.com
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Cataracts Source: Integrative Medicine Communications; www.drkoop.com Celiac Disease Source: Healthnotes, Inc. www.healthnotes.com Chronic Fatigue Syndrome Source: Healthnotes, Inc. www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc. www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com Cluster Headache Source: Healthnotes, Inc. www.healthnotes.com Colon Cancer Source: Healthnotes, Inc. www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Congestive Heart Failure Source: Healthnotes, Inc. www.healthnotes.com Conjunctivitis Source: Integrative Medicine Communications; www.drkoop.com Conjunctivitis and Blepharitis Source: Healthnotes, Inc. www.healthnotes.com Crohn's Disease Source: Healthnotes, Inc. www.healthnotes.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Cutaneous Drug Reactions Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Dupuytren's Contracture Source: Healthnotes, Inc. www.healthnotes.com
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Eczema Source: Healthnotes, Inc. www.healthnotes.com Eczema Source: Integrative Medicine Communications; www.drkoop.com Eczema Source: Prima Communications, Inc.www.personalhealthzone.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Endometriosis Source: Healthnotes, Inc. www.healthnotes.com Endometriosis Source: Integrative Medicine Communications; www.drkoop.com Epilepsy Source: Healthnotes, Inc. www.healthnotes.com Epstein-Barr Virus Source: Integrative Medicine Communications; www.drkoop.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Fever of Unknown Origin Source: Integrative Medicine Communications; www.drkoop.com Fibrocystic Breast Disease Source: Healthnotes, Inc. www.healthnotes.com Frostbite Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc. www.healthnotes.com Gout Source: Healthnotes, Inc. www.healthnotes.com Gout Source: Integrative Medicine Communications; www.drkoop.com Hair Disorders Source: Integrative Medicine Communications; www.drkoop.com
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Hair Loss Source: Integrative Medicine Communications; www.drkoop.com Hay Fever Source: Healthnotes, Inc. www.healthnotes.com Hay Fever Source: Integrative Medicine Communications; www.drkoop.com Hemophilia Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc. www.healthnotes.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Triglycerides Source: Healthnotes, Inc. www.healthnotes.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc. www.healthnotes.com Hives Source: Healthnotes, Inc. www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Insect Bites and Stings Source: Integrative Medicine Communications; www.drkoop.com Kidney Stones Source: Healthnotes, Inc. www.healthnotes.com
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Laryngitis Source: Integrative Medicine Communications; www.drkoop.com Low Back Pain Source: Healthnotes, Inc. www.healthnotes.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Lyme Disease Source: Integrative Medicine Communications; www.drkoop.com Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Mononucleosis Source: Integrative Medicine Communications; www.drkoop.com Multiple Sclerosis Source: Healthnotes, Inc. www.healthnotes.com Multiple Sclerosis Source: Integrative Medicine Communications; www.drkoop.com Nail Disorders Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Healthnotes, Inc. www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com
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Pain Source: Healthnotes, Inc. www.healthnotes.com Pancreas, Inflammation of Source: Integrative Medicine Communications; www.drkoop.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Healthnotes, Inc. www.healthnotes.com Pericarditis Source: Integrative Medicine Communications; www.drkoop.com Pertussis Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Photosensitivity Source: Healthnotes, Inc. www.healthnotes.com Pink Eye Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Healthnotes, Inc. www.healthnotes.com Psoriasis Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Prima Communications, Inc.www.personalhealthzone.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Reiter's Syndrome Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Healthnotes, Inc. www.healthnotes.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com
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Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Seborrheic Dermatitis Source: Healthnotes, Inc. www.healthnotes.com Serum Sickness Source: Integrative Medicine Communications; www.drkoop.com Shingles and Postherpetic Neuralgia Source: Healthnotes, Inc. www.healthnotes.com Shock Source: Integrative Medicine Communications; www.drkoop.com Sinus Congestion Source: Healthnotes, Inc. www.healthnotes.com Sinus Infection Source: Integrative Medicine Communications; www.drkoop.com Sinusitis Source: Healthnotes, Inc. www.healthnotes.com Sinusitis Source: Integrative Medicine Communications; www.drkoop.com Sprains and Strains Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Syncope Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc. www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Temporomandibular Joint Dysfunction Source: Integrative Medicine Communications; www.drkoop.com
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Tendinitis Source: Healthnotes, Inc. www.healthnotes.com Tendinitis Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Healthnotes, Inc. www.healthnotes.com Thyroid Inflammation Source: Integrative Medicine Communications; www.drkoop.com Thyroiditis Source: Integrative Medicine Communications; www.drkoop.com TMJ Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc. www.healthnotes.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Ulcers Source: Prima Communications, Inc.www.personalhealthzone.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Vaginal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 Deficiency Source: Healthnotes, Inc. www.healthnotes.com Whooping Cough Source: Integrative Medicine Communications; www.drkoop.com Wounds Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Healthnotes, Inc. www.healthnotes.com •
Alternative Therapy Apitherapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,669,00.html Aston-patterning Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10118,00.html Chiropractic Source: Integrative Medicine Communications; www.drkoop.com Testing for Stomach Acidity Source: Healthnotes, Inc. www.healthnotes.com •
Herbs and Supplements 7-KETO Source: Healthnotes, Inc. www.healthnotes.com Acetaminophen Source: Healthnotes, Inc. www.healthnotes.com Adrenal complex Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,994,00.html Adrenal Extract Source: Healthnotes, Inc. www.healthnotes.com Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Aloe Source: Healthnotes, Inc. www.healthnotes.com Aloe vera Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Androstenedione Source: Healthnotes, Inc. www.healthnotes.com Androstenedione Source: Prima Communications, Inc.www.personalhealthzone.com Anti-Inflammatory Drugs Source: Prima Communications, Inc.www.personalhealthzone.com
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Arctostaphylos uva ursi Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Ashwagandha Alternative names: Withania somniferum Source: Healthnotes, Inc. www.healthnotes.com Ashwagandha Source: Prima Communications, Inc.www.personalhealthzone.com Aspirin/Acetaminophen Alternative names: Buffets Vanquish, Extra Strength Excedrin, Gelpirin, Goody's, Maximum Pain Relief Pamprin, Menoplex, Supac Source: Prima Communications, Inc.www.personalhealthzone.com Bearberry Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Bearberry Source: Integrative Medicine Communications; www.drkoop.com Beargrape Source: Integrative Medicine Communications; www.drkoop.com Beargrape Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Bitter Melon Alternative names: Momordica charantia Source: Healthnotes, Inc. www.healthnotes.com Boswellia Alternative names: Boswellia serrata Source: Healthnotes, Inc. www.healthnotes.com Boswellia Source: Prima Communications, Inc.www.personalhealthzone.com Boswellia Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,759,00.html Bovine Colostrum Source: Healthnotes, Inc. www.healthnotes.com Bromelain Source: WholeHealthMD.com, LLC. www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Bupleurum Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc. www.healthnotes.com Butcher’s Broom Alternative names: Ruscus aculeatus Source: Healthnotes, Inc. www.healthnotes.com Butcher's broom Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10010,00.html Cartilage (Bovine and Shark) Source: Healthnotes, Inc. www.healthnotes.com Cascara sagrada Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10013,00.html Cat's Claw Alternative names: Uncaria tomentosa Source: Integrative Medicine Communications; www.drkoop.com Cayenne Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,765,00.html Celecoxib Source: Healthnotes, Inc. www.healthnotes.com Cetyl Myristoleate Source: Healthnotes, Inc. www.healthnotes.com Cherry fruit extract Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10015,00.html Chrysanthemum parthenium Alternative names: Feverfew Source: Integrative Medicine Communications; www.drkoop.com
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Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Cornus Alternative names: Dogwood; Cornus florida & officinalis Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Cysteine Source: Healthnotes, Inc. www.healthnotes.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc. www.healthnotes.com Dehydroepiandrosterone (DHEA) Alternative names: DHEA Source: Integrative Medicine Communications; www.drkoop.com DHA Alternative names: Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com DHEA Alternative names: Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com DHEA Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10022,00.html DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Diclofenac Source: Healthnotes, Inc. www.healthnotes.com Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Diuretics Source: Healthnotes, Inc. www.healthnotes.com
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Docosahexaenoic Acid (DHA) Alternative names: DHA Source: Integrative Medicine Communications; www.drkoop.com Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com Dong quai (angelica) Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,774,00.html Echinacea Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Eicosapentaenoic Acid (EPA) Alternative names: EPA Source: Integrative Medicine Communications; www.drkoop.com EPA Alternative names: Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com Estrogens (Combined) Source: Healthnotes, Inc. www.healthnotes.com Etodolac Source: Healthnotes, Inc. www.healthnotes.com False Unicorn Alternative names: Chamaelirium luteum Source: Healthnotes, Inc. www.healthnotes.com False unicorn root Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10075,00.html Fenugreek Alternative names: Trigonella foenum-graecum Source: Healthnotes, Inc. www.healthnotes.com Feverfew Alternative names: Tanacetum parthenium, Chrysanthemum parthenium Source: Integrative Medicine Communications; www.drkoop.com Feverfew Alternative names: Chrysanthemum parthenium Source: Integrative Medicine Communications; www.drkoop.com Flurbiprofen Source: Healthnotes, Inc. www.healthnotes.com
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Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc. www.healthnotes.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Ginseng (Panax) Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10029,00.html GLA Source: Integrative Medicine Communications; www.drkoop.com Glucosamine Source: Integrative Medicine Communications; www.drkoop.com Glucosamine Source: Prima Communications, Inc.www.personalhealthzone.com Glucosamine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,790,00.html Glycyrrhiza glabra Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Guggul Alternative names: Commiphora mukul Source: Healthnotes, Inc. www.healthnotes.com Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Herbal digestive formula Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10104,00.html
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Ibuprofen Source: Healthnotes, Inc. www.healthnotes.com Indomethacin Source: Healthnotes, Inc. www.healthnotes.com Inhalant, Systemic, and Topical Corticosteroids Source: Integrative Medicine Communications; www.drkoop.com Inhaled Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Ketoprofen Source: Healthnotes, Inc. www.healthnotes.com Ketorolac Source: Healthnotes, Inc. www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc. www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Licorice Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lotrisone Source: Healthnotes, Inc. www.healthnotes.com Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Melatonin Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com
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Melatonin Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Mifepristone Source: Healthnotes, Inc. www.healthnotes.com Misoprostol Source: Healthnotes, Inc. www.healthnotes.com Momordica Alternative names: Bitter Gourd, Karela; Momordica charantia Linn. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Monophasic, Biphasic, and Triphasic Preparations Source: Integrative Medicine Communications; www.drkoop.com Mycolog II Source: Healthnotes, Inc. www.healthnotes.com Nabumetone Source: Healthnotes, Inc. www.healthnotes.com N-Acetyl Cysteine Source: Healthnotes, Inc. www.healthnotes.com Nettle Alternative names: Urtica dioica Source: Healthnotes, Inc. www.healthnotes.com Nettle Alternative names: Stinging Nettle Source: Integrative Medicine Communications; www.drkoop.com Non-steroidal Anti-Inflammatory Drugs Source: Healthnotes, Inc. www.healthnotes.com Nonsteroidal Anti-Inflammatory Drugs Source: Prima Communications, Inc.www.personalhealthzone.com Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Source: Integrative Medicine Communications; www.drkoop.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Oral Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com
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Oxaprozin Source: Healthnotes, Inc. www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Piroxicam Source: Healthnotes, Inc. www.healthnotes.com Pregnenolone Source: Healthnotes, Inc. www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc. www.healthnotes.com Pygeum Alternative names: African Prune; Pygeum africanum Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Rofecoxib Source: Healthnotes, Inc. www.healthnotes.com Sabal serrulata Source: Integrative Medicine Communications; www.drkoop.com S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com Salsalate Source: Healthnotes, Inc. www.healthnotes.com Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org SAMe Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-adenosylmethionine) Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html
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Sarsaparilla Alternative names: Smilax spp. Source: Healthnotes, Inc. www.healthnotes.com Saw Palmetto Alternative names: Serenoa repens, Sabal serrulata Source: Integrative Medicine Communications; www.drkoop.com Serenoa repens Source: Integrative Medicine Communications; www.drkoop.com Smilax Alternative names: Sarsaparilla; Smilax glabra Roxb. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Spanish Licorice Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Stanozolol Source: Healthnotes, Inc. www.healthnotes.com Sulindac Source: Healthnotes, Inc. www.healthnotes.com Suma Alternative names: Pfaffia paniculata , Hebanthe paniculata Source: Healthnotes, Inc. www.healthnotes.com Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Tanacetum parthenium Alternative names: Feverfew Source: Integrative Medicine Communications; www.drkoop.com Tobradex Source: Healthnotes, Inc. www.healthnotes.com Topical Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Tramadol Source: Healthnotes, Inc. www.healthnotes.com Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
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Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Uncaria CatClaw Alternative names: Cat's Claw, Uno de Gato; Uncaria tomentosa (Willd.) D.C. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Uncaria tomentosa Alternative names: Cat's Claw Source: Integrative Medicine Communications; www.drkoop.com Urtica dioica Alternative names: Stinging Nettle Source: Integrative Medicine Communications; www.drkoop.com Urtica urens Alternative names: Stinging Nettle Source: Integrative Medicine Communications; www.drkoop.com Urtica urens Source: Integrative Medicine Communications; www.drkoop.com Uva Ursi Alternative names: Arctostaphylos uva ursi, Bearberry, Beargrape Source: Integrative Medicine Communications; www.drkoop.com VacciniumB Alternative names: Bilberry; Vaccinium myrtillus L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Valproic Acid Source: Prima Communications, Inc.www.personalhealthzone.com Verbascum Alternative names: Mullein; Verbascum thapsus L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org White willow bark Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10069,00.html Wild Yam Alternative names: Dioscorea villosa Source: Healthnotes, Inc. www.healthnotes.com Wild Yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com
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Wild Yam Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Willow Bark Alternative names: There are several species of willow includingSalix alba, Salix nigra, Salix fragilis, Salix purpurea, Salix babylonica, White Willow, European Willow, Black Willow, Pussy Willow, Crack Willow, Purple Willow, Weeping Willow, Liu-zhi Source: Integrative Medicine Communications; www.drkoop.com Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON STEROIDS Overview In this chapter, we will give you a bibliography on recent dissertations relating to steroids. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “steroids” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on steroids, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Steroids ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to steroids. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Stereospecific Synthesis or Ring A-aromatic Steroids. Cyclobutanes in Organic Synthesis by Macalpine, Gerald Arthur; Phd from The University of New Brunswick (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK16243
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An Approach to the Conformational Analysis of the Side Chain of Carbon-13 Labeled Cholesterol and Related Steroids by Alexander, John Ulmos; Phd from University of California, Riverside, 2002, 261 pages http://wwwlib.umi.com/dissertations/fullcit/3071434
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An Experimental Investigation of the Influence of Glycosides, Steroids, and Other Plant Constituents on the Feeding Behaviour Development and Survival of the Twostriped Grasshopper, Melanoplus Bivattatus (say), Acrididae: Orthoptera by Harley, K. L. S; Phd from The University of Manitoba (canada), 1965 http://wwwlib.umi.com/dissertations/fullcit/NK00040
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Anabolic Androgenic Steroids and the Brain: Studies of Neurochemical and Behavioural Changes Using an Animal Model by Steensland, Pia Gerd; Phd from Uppsala Universitet (sweden), 2002, 60 pages http://wwwlib.umi.com/dissertations/fullcit/f305361
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Anabolic Steroid Glucuronides: Enzyme-assisted Synthesis and Liquid Chromatographic-mass Spectrometric Analysis by Kuuranne, Tiia Katjaana; Phd from Helsingin Yliopisto (finland), 2003, 107 pages http://wwwlib.umi.com/dissertations/fullcit/f43809
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Anabolic-androgenic Steroid Use: the Knowledge, Attitudes and Behavior of High School Football Players (steroid Use, Drug Education) by Lowcock, Phillip Wayne, Phd from University of Kansas, 1992, 108 pages http://wwwlib.umi.com/dissertations/fullcit/9323032
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Cationic Corticosteroids for Gene Delivery and As Controlled Release Antiinflammatory Agents by Gruneich, Jeffrey Alan Miner; Phd from University of Pennsylvania, 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3073005
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Characterisation of a Porcine 3beta-hydroxysteroid Dehydrogenase/delta5-delta4isomerase Gene to Decrease the Level of Androstenone by Von Teichman-logischen Kohler, Adriana Fiona; Drscnat from Eidgenoessische Technische Hochschule Zuerich (switzerland), 2002 http://wwwlib.umi.com/dissertations/fullcit/f291697
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Chromatography and Mass Spectrometry of Sterically Crowded Trialkylsilyl Derivatives of Nucleosides and Steroids by Quilliam, Michael A; Phd from The University of Manitoba (canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK30067
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Conversion of Steroids by Chromaffin Tissue by Carballeira, Andrés; Advdeg from Mcgill University (canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00797
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Determination of Timp-2 in Bovine Granulosa Cells and Its Relationship to Follicular Steroids by Willard, Erica May; Ms from Mississippi State University, 2002, 99 pages http://wwwlib.umi.com/dissertations/fullcit/1410602
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Effect of Androgenic Steroids on Baroreflex Sensitivity in the Conscious Spraguedawley Male Rat by Ward, Gregg Ricardo; Phd from East Carolina University, 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3056056
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Effects of Anabolic Steroids on Selected Physiological Measures Taken on Albino Rats by Cheek, Don Lynn, Edd from University of Arkansas, 1972, 108 pages http://wwwlib.umi.com/dissertations/fullcit/7210201
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Effects of Salmon Gonadotrophin and Sex Steroids on Plasma Lipids in the Goldfish, Carassius Auratus by Weigand, Murray Douglas; Phd from University of Alberta (canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK43586
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Effects of Sex Steroids and Diet on Adipose Distribution and Cardiovascular Disease Risk Factors by Shultz, Jennifer Marie; Phd from University of Washington, 2002, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3041057
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Effects of Some Steroids and Benzanthracenes on Embryonic Mouse Skin in Organ Culture by Singh, Amreek; Advdeg from University of Guelph (canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK09040
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Effects of Steroid Hormones on Cytochrome P450 Enzyme Activity in Women by Zhang, Yanhua; Msc from University of Toronto (canada), 2002, 127 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74134
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Epidemiological and Neurobiological Evidence for Misuse of Anabolic-androgenic Steroids by Kindlundh, Anna Moon Sun; Phd from Uppsala Universitet (sweden), 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/f686561
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Formation of Steroids in Human Pregnancy by Brisson, Gilles; Phd from Mcgill University (canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK24275
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Impact of Anti-inflammatory Medications, Methotrexate, and Steroidal Medications on Psychosocial Functioning and Medical Status in Juvenile Rheumatoid Arthritis Patients by Ryser, Christina Nicole; Phd from The University of Texas Southwestern Medical Center at Dallas, 2002 http://wwwlib.umi.com/dissertations/fullcit/f865233
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Improving Adherence to Inhaled Corticosteroids in Children with Asthma by Kamps, Jodi Lynn; Phd from University of Kansas, 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/3071113
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In Vivo and in Vitro Interactions of Steroids with Metals by Pouskoueli, G; Phd from Mcgill University (canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK52088
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Indiana High School Football Players' Attitude, Knowledge, and Use of Anabolicandrogenic Steroids by Stilger, Vincent Gerard, Hsd from Indiana University, 1993, 169 pages http://wwwlib.umi.com/dissertations/fullcit/9423589
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Initial Evaluation of a Novel Method to Assess Corticosteroid Responsiveness in Chronic Obstructive Pulmonary Disease (copd) by Ghiculete, Daniela; Msc from University of Toronto (canada), 2002, 90 pages http://wwwlib.umi.com/dissertations/fullcit/MQ73830
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La 17beta-hydroxysteroide Deshydrogenase Humaine: Etude Des Relations Structurefonction Par La Mutagenase Dirigee Et Mecanisme Cinetique by Huang, Yi-wei; Phd from Universite Laval (canada), 2002, 275 pages http://wwwlib.umi.com/dissertations/fullcit/NQ73749
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Metabolism of Neutral Steroids in the Human Placenta and Fetus by Ling, William Y; Advdeg from Mcgill University (canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK07287
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Myocardial Structure and Function Differences between Steroid-using and Nonsteroid-using Elite Powerlifters and Endurance Athletes by Climstein, Mike, Phd from Oregon State University, 1990, 113 pages http://wwwlib.umi.com/dissertations/fullcit/9032653
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Neurosteroids Modulate Ionotropic Glutamate Receptor-induced Dopamine Release and Locomotor Activity in the Rat by Sadri-vakili, Ghazaleh; Phd from Boston University, 2003, 194 pages http://wwwlib.umi.com/dissertations/fullcit/3084508
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On the Synthesis of Aminoglycosides of Cardioactive Steroids by Finizia, Gabriella; Phd from The University of New Brunswick (canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL55772
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Ovarian Function, Circulating Steroids, and Early Embryonic Development in Dairy Cattle by Sartori Filho, Roberto; Phd from The University of Wisconsin - Madison, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3072874
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Ovarian Steroid Modulation of Ethanol Self-administration in the Female Long-evans Rat by Ford, Matthew Martin; Phd from Wake Forest University, the Bowman Gray School of Medicine, 2002, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3058870
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Parachors in Drug Design : Structure-activity Correlation Study of Steroids by Ahmad, Parvez; Phd from University of Guelph (canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK37377
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Prevalence of Illicit Anabolic Steroid Use among Rural-agrarian College Age Students by Scott, Robert Frank, Jr., Phd from Sam Houston State University, 1993, 203 pages http://wwwlib.umi.com/dissertations/fullcit/9333586
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Progesterone and Corticosteroid Interaction during Pregnancy in Ewes by Hua, Yi; Phd from University of Florida, 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3084005
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Regulation of Porcine Testicular Steroidogenesis and Implications for Reducing the Incidence of Boar Taint by Gregor, Douglas Leigh; Phd from The Pennsylvania State University, 2002, 116 pages http://wwwlib.umi.com/dissertations/fullcit/3051658
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Role of Ovarian Steroids on Estrus Control in Bovine by Rajamahendran, Rajadurai; Phd from Mcgill University (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK31866
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Sex- and Training-related Differences in Metabolic, Sex Steroid and Growth Hormone Responses during Prolonged Exercise by Bunt, Joy Carol, Phd from University of Illinois at Urbana-champaign, 1985, 267 pages http://wwwlib.umi.com/dissertations/fullcit/8521729
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Sex Steroids, Sex Chromosome Genes, and a Gynandromorphic Finch: Novel Mechanisms of Brain Sexual Differentiation by Agate, Robert Jon; Phd from University of California, Los Angeles, 2003, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3081160
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Some Effects of Anabolic Steroids during Weight Training by Munson, Alex Robert, Edd from University of Southern California, 1970, 156 pages http://wwwlib.umi.com/dissertations/fullcit/7011379
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Steroid Sulfatase Expression in Osteoblast-like Cell Lines: a Regulatory Role for Glucocorticoids? by Olshanski, Anne Marie; Ms from Duquesne University, 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/1409927
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Steroidogenesis and the Role of Steroids in the Endocrine Control of Oogenesis and Vitellogenesis in the Goldfish, Carassius Auratus by Koo, Khay Huat; Phd from The University of British Columbia (canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK22137
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Steroids, Dietary Lipids, Resection and Intestinal Adaptation by Thiesen, Aducio Leonel, Junior; Phd from University of Alberta (canada), 2002, 469 pages http://wwwlib.umi.com/dissertations/fullcit/NQ68629
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Steroids: the Synthesis of Potential Estrogen Precursors by Van Tongerloo, Alex; Phd from University of Ottawa (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12383
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Studies in Steroids and Alkaloids by Vlattas, Isidorus; Phd from The University of British Columbia (canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00486
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Studies in the Fields of Steroids Alkaloids by Cretney, W. J; Advdeg from The University of British Columbia (canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK03036
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Studies in the Synthesis and Biological Properties of Cyclopropane Containing Steroids by Wie, Chwi Wan; Phd from The University of Manitoba (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK30082
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Studies of Steroid Metabolism in Dairy Cattle by Sangsritavong, Siwat; Phd from The University of Wisconsin - Madison, 2002, 206 pages http://wwwlib.umi.com/dissertations/fullcit/3060537
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Studies of the Sulfonation and Neuroprotective Actions of the Neurosteroids Dhea and Estradiol in Rat Brain by Sanchez, Rosa Isela; Phd from Rutgers the State U. of N.j. - New Brunswick and U.m.d.n.j., 2002, 186 pages http://wwwlib.umi.com/dissertations/fullcit/3055132
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Studies on Testosterone and Ring D Hydroxylated Steroids in Human Pregnancy by Stern, Michael D; Phd from Mcgill University (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12052
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Studies on the Metabolism of Pregnenolone in the Pregnant Rhesus Monkey and 15 Alpha-hydroxylated Steroids in Human Pregnancy by Stanczyk, Frank Z; Phd from Mcgill University (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12051
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Studies on the Metabolism of Some Steroids in Rabbits by Kim, Ryung-soon Song; Phd from The University of Manitoba (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK26361
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Studies on the Regulation of Acth Release in Vivo and in Vitro; the Role of Steroids and Neurohypophysical Hormones by Pollock, J. J; Phd from The University of Manitoba (canada), 1965 http://wwwlib.umi.com/dissertations/fullcit/NK00062
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Syntheses of 11- and 17-substituted Steroids of Biological Interest Reactions of Lithium Alkylcuprates with Alpha-halogenated Ketones by Lourdusamy, Mary Mettilda; Phd from Universite Laval (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL49494
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Synthesis of Bridged Steroids by Walliser, Françoise Martine; Phd from University of Toronto (canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK42337
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Synthetic and High Field Nmr Studies of Organometallic Derivatives of Steroids by Perrier, Richard Eugene; Phd from Mcmaster University (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL57972
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The Capacity of Rat Sertoli Cells in Vitro to Metabolize Carbon(19) Steroids and the Age Related Variation and Fsh Effect on Steroidogenic Enzyme Activites by Welsh, Michael John; Phd from The University of Western Ontario (canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK31669
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The Effects of an Anabolic Steroid (oxandrolone) on Reproductive Development in the Male and Female Rat by Grokett, Bernard H., Phd from University of Southern California, 1992 http://wwwlib.umi.com/dissertations/fullcit/f585588
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The Effects of Anabolic Steroids on Volitional Exercise, Nutritional Intake, and Body Weight in Exercising and Non-exercising Rats by Swiergosz, Thomas John, Phd from The University of Toledo, 1998, 55 pages http://wwwlib.umi.com/dissertations/fullcit/9916208
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The Effects of Anabolic-androgenic Steroids on Gaba(a) Receptor Function and Expression by Mcintyre, Kerry Lee; Phd from Dartmouth College, 2002, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3070243
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The Effects of Training on Selected Steroid Hormones: Response to Exercise in Postmenopausal Women by Richardson-lehnhard, Holly Jo, Phd from The Ohio State University, 1984, 82 pages http://wwwlib.umi.com/dissertations/fullcit/8426462
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The Interrelationship between Thyroid Hormones and Ovarian Sex Steroids in Rainbow Trout, Salmo Gairdneri by Cyr, Daniel Gabriel; Phd from The University of Manitoba (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL48071
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The Role of Sulfate Conjugates in the Formation of Adrenal Steroids by Killinger, Donald W; Advdeg from Mcgill University (canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02150
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The Total Synthesis of Bridged Ring a Steroids by Douglas, Stephen Paul; Phd from University of Toronto (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39170
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND STEROIDS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning steroids.
Recent Trials on Steroids The following is a list of recent trials dedicated to steroids.8 Further information on a trial is available at the Web site indicated. •
An open-label pilot study of Coenzyme Q10 in steroid-treated Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the nutritional supplement Coenzyme Q10 when added to steroids as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should be on a stable dose of steroids for at least six months, and will remain on their usual dose throughout the study. They will complete two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Coenzyme Q10. Once Coenzyme Q10 therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Coenzyme Q10 until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033189
8 These
are listed at www.ClinicalTrials.gov.
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Combination Chemotherapy Plus Steroid Therapy in Treating Children With Acute Lymphoblastic Leukemia or Lymphoblastic Non-Hodgkin's Lymphoma Condition(s): acute undifferentiated leukemia; childhood acute lymphoblastic leukemia; childhood lymphoblastic lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Children's Leukemia Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy plus steroid therapy is more effective for acute lymphoblastic leukemia or lymphoblastic non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus steroid therapy in treating children who have acute lymphoblastic leukemia or lymphoblastic non-Hodgkin's lymphoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003728
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Dose-finding study using pentostatin for injection in the treatment of steroidrefractory aGvHD Condition(s): Acute Graft Versus Host Disease Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine a safe and effective dose of pentostatin in steroidrefractory aGvHD and to identify the minimal effective dose of pentostatin defined as the lowest dose that produces a response in 20% or more of patients while producing treatment failure (defines as death, grade 3/4 toxicity, or progressive disease) in 40% or less of patients. Phase(s): Phase I; Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032773
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Early Diagnosis of Steroid-Responsive & No-Responsive Hearing Loss Condition(s): Hearing Loss Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Purpose - Excerpt: Tinnitus is a prevalent issue for veterans who are proportionally more hearing-impaired than the civilian population. This study will be conducted as three concurrent projects designed to develop an efficient clinical technique to quantify tinnitus perception: (1)Laboratory development of the automated technique for comprehensive tinnitus quantification;(2)Development of a technique to test for tinnitus
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"malingering"; and (3)Evaluation of the automated technique in the clinical environment. Phase(s): Phase II Study Type: Observational Contact(s): Steven Hefeneider, Ph.D. (503) 220-3428
[email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00013468 •
Extracorporeal Photopheresis to Maintain Symptoms Remission During Steroid Withdrawal in Patients with Steroid-Dependent Crohn's Disease Condition(s): Crohn Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the safety and effectiveness of extracorporeal photopheresis (ECP) in controlling Crohn's disease symptoms as patients taper their corticosteroid dose. Crohn's disease is a chronic inflammatory bowel disease. Patients commonly have chronic diarrhea with abdominal pain, loss of appetite and weight loss. Acute disease flares are treated with large doses of corticosteroids, but long-term use of these drugs can have harmful side effects. ECP (described below), is approved to treat skin symptoms associated with a type of cancer called cutaneous T-cell lymphoma and has been used experimentally in conditions involving abnormal inflammation. Patients 18 years of age and older who have had Crohn's disease for at least 6 months, who are corticosteroid-dependent, and whose symptoms are controlled well enough so that their Crohn's Disease Activity Index (CDAI) is less than 220, may be eligible for this study. Candidates will be screened with a medical history and review of medical records, physical examination, electrocardiogram, blood tests, urine pregnancy test for women of childbearing potential, and a questionnaire about how Crohn's disease affects their life and activities. Patients with a CDAI score of less than 150 will begin ECP treatments as soon as possible. Those with scores from 150 to 219 will have their corticosteroid dose increased enough to bring their CDAI score to below 150 before beginning ECP. Patients who do not achieve a CDAI of less than 150 after 4 to 6 weeks of increased corticosteroids will be excluded from the study. Participants will have ECP treatments for 2 consecutive days every 2 weeks for 24 weeks, for a total of 26 treatments. For ECP, patients undergo leukapheresis, a method of collecting large numbers of white blood cells, or leukocytes-cells that may be responsible for many of the medical problems in Crohn's disease. Whole blood is collected through a needle in an arm vein, similar to donating a unit of blood. The blood flows through a machine that separates it into its components by spinning. The white cells are removed and collected in a plastic bag, and the red blood cells and plasma are returned to the patient's bloodstream through the same needle. The collected white cells are mixed with a drug called UVADEX(r) (Registered Trademark), exposed to ultraviolet (UVA) light, and then returned to the patients' bloodstream. (The UVADEX allows the blood cells to absorb more UVA.) The UVA changes the cells in a way that, once they are back in the body, they cause changes in other cells like them. Each ECP treatment takes 3 to 4 hours. On the first day of each 2-day treatment, patients will undergo a review of symptoms, check of vital signs, and blood draw. They will complete a CDAI diary for 7 days before the first of the two ECP treatments and a questionnaire about their life and activities at 4-week intervals. During the ECP treatment period, corticosteroids will be slowly reduced as long as disease symptoms do not worsen. Patients whose disease remains under control with cessation of all steroids may begin maintenance ECP, 2 days in a row every 4 weeks for an
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additional 20 weeks (another 10 treatments), with the same follow-up as described above, and a full physical examination 4 weeks after the final treatment. Patients who were able to reduce, but not stop, steroid treatment may be considered for maintenance therapy if it is thought that continuing treatment may enable further reduction of steroids. Patients whose disease symptoms worsen with ECP or who have not been able to decrease their steroid dose will not be eligible for maintenance therapy and their participation in the study will end. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056355 •
KUL0401: An open-label pilot study of Oxatomide in steroid-naive Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the mast cell stabilizer Oxatomide as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should not have taken steroids to treat DMD for at least twelve months, and should not have taken any nutritional supplements for at least three months. Subjects will complete a two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Oxatomide. Once Oxatomide therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Oxatomide until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033813
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Repeat Antenatal Steroids Trial Condition(s): Complications, Pregnancy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: A course of steroids given to a mother who is in labor with a premature fetus will reduce the risk of the premature infant dying or having serious complications. This trial will test whether more than one course of antenatal steroids is more beneficial or risky to the infant than a single course. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015002
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Steroid Therapy in Autoimmune Premature Ovarian Failure Condition(s): Autoimmune Disease; Infertility; Premature Ovarian Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: No therapy for infertile patients with premature ovarian failure has been proven effective. Some anecdotal reports have suggested that high dose, long term prednisone (steroid) therapy may be useful in treating autoimmune ovarian failure. However, prednisone, when used in high-doses for long periods of time has substantial side effects, including aseptic necrosis of bone where portions of bone die without the presence of infection and are surrounded by healthy tissue. Aseptic necrosis of bone often requires major surgical treatment. Even with this known level of risk, patients with premature ovarian failure are being treated based on this anecdotal evidence. This study will test the hypothesis that a lower risk therapy (alternate-day, lower dose, shorter-term prednisone) will cause a remission of autoimmune ovarian failure. There is no reliable blood test to identify patients who have premature ovarian failure. Therefore, all patients must undergo a laparoscopic ovarian biopsy to confirm the presence of an auto immune reaction in the ovaries (autoimmune oophoritis). Laparoscopy is a surgical procedure that allows doctors to explore the abdomen using a camera-like device called a laparoscope. The procedure has been used clinically by some reproductive endocrinologists to identify patients with premature ovarian failure who have an autoimmune mechanism for the disorder. The treatment will be deemed successful based on the return of ovulation as determined by weekly serum progesterone levels. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001306
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Steroid Treatment for Kidney Disease Condition(s): Nephrosis; Focal Lipoid Glomerulosclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Focal segmental glomerulosclerosis (FSGS) and minimal change disease are kidney diseases that are associated with increased excretion of protein in the urine. Approximately half of FSGS patients will lose kidney function within 8 years of diagnosis and will require dialysis. The purpose of this study is to determine whether intermittent oral steroid therapy can cause sustained remission of FSGS and MCD. Approximately 70 participants, including adults and children older than age 2, will be enrolled in this study. They will receive 48 doses of oral dexamethasone over a period of 48 weeks. One group will take two daily doses every 2 weeks; the other group will take four daily doses every 4 weeks. Doctors will monitor participants before, during, and after the steroid treatment with extensive exams and testing. At the completion of the study, researchers will evaluate the safety and efficacy of the drug treatment. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065611
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Steroid Withdrawal in Pediatric Kidney Transplant Recipients Condition(s): End-Stage Renal Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to examine the effects of withdrawing steroids on graft rejection and kidney functions in kidney transplant recipients. Graft survival has improved in recent years in children with kidney transplants. One bad side effect of steroid maintenance therapy has been growth retardation. Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies. If steroids are removed, children might catch up in their growth and also might have fewer side effects of other kinds. This study measures whether steroid therapy can be withdrawn in a way that does not increase graft rejection. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023244
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Study of Depression, Peptides, and Steroids in Cushing's Syndrome Condition(s): Cushing's Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); University of Michigan Purpose - Excerpt: Objectives: I. Study the relationship between dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and disorders of mood, vegetative function, and cognition in patients with Cushing's disease. II. Identify subgroups of patients with Cushing's disease who differ in the presence and severity of the depressive syndrome, and uncover HPA axis dysregulation differences among them using corticotropinreleasing hormone, metyrapone, and dexamethasone challenge testing. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004334
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Chemotherapy Plus Steroid Therapy in Treating Patients With Multiple Myeloma Condition(s): refractory plasma cell neoplasm; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma Study Status: This study is no longer recruiting patients. Sponsor(s): Riverside Haematology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Steroids, such as dexamethasone or prednisolone, may help relieve some of the side effects of chemotherapy. It is not yet known which regimen of chemotherapy plus steroid therapy is more effective in treating patients with multiple myeloma. PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of chemotherapy plus steroid therapy in treating patients with multiple myeloma that has recurred for the first time. Phase(s): Phase III
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003603 •
Comparison of Antibody Therapies in Treating Patients With Graft- Versus-Host Disease That Does Not Respond to Steroid Therapy Condition(s): Leukemia; Testicular Cancer; ovarian epithelial cancer; Lymphoma; Breast Cancer; Multiple Myeloma; kidney tumor Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Jonsson Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known which antibody therapy regimen is more effective for graft-versus-host disease. PURPOSE: Randomized phase II/III trial to compare the effectiveness of two different antibody therapy regimens in treating patients who have graft-versus-host disease that does not respond to steroid therapy. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012077
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Creatine and Glutamine in Steroid-Naive Duchenne Muscular Dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is no longer recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the effectiveness of glutamine and creatine as a possible therapy for DMD. Boys with DMD who are enrolled in this trial will be randomly chosen to receive creatine monohydrate or glutamine or an inactive placebo orally for six months. Once a month during the six-month treatment period, the study participants will have their muscle strength evaluated using manual and computerized testing methods. This study will be conducted at several CINRG Centers throughout the U.S., Belgium, Israel and Puerto Rico. This study is supported by the Muscular Dystrophy Association. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016653
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Once-A-Month Steroid Glomerulosclerosis
Treatment
for
Patients
with
Focal
Segmental
Condition(s): Glomerulonephritis; Nephrotic Syndrome Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Purpose - Excerpt: This study will test the safety and effectiveness of a monthly dosing regimen of dexamethasone-a strong steroid medication-to treat patients with focal segmental glomerulosclerosis (FSGS). Patients with this disease have kidney fibrosis (scarring) and proteinuria (excessive excretion of protein in the urine) that, in about half of the patients eventually requires kidney dialysis or transplant. Currently, the most effective treatment for FSGS is high-dose steroids (prednisone) taken daily for 4 to 6 months. However, only about 30 percent of patients respond to this treatment, and it causes serious side effects in many patients. Other drugs, such as cyclosporin and cyclophosphamide, improve proteinuria in even fewer patients (about 10 percent) and also have serious side effects. This study will explore whether a monthly pulse dose of steroids will achieve disease remission with less toxicity. Adults and children with FSGS who: 1) have not received steroid treatment, or 2) could not tolerate daily steroid treatment, or 3) relapsed after conventional steroid treatment may be eligible for this study. Those enrolled will take dexamethasone by mouth for 4 days every 4 weeks for a total of 8 months. Patients will undergo various tests before treatment starts (baseline), during the course of treatment, and in follow-up visits to evaluate the effects of treatment as follows: 1. Review of kidney biopsy, medical evaluation, measurement of total daily urine protein excretion and kidney function, psychiatric testing for depression or other mood disorder 2. Measurements of blood pressure, blood chemistries and urine protein excretion - monthly during treatment 3. Questionnaire about the effects of treatment, if any, on mood and feelings - monthly during treatment 4. Photographs of the face and body (in underwear or shorts and tank top) to evaluate body fat distribution- baseline and 8 months 5. Eye examinations for cataracts and glaucoma - baseline and 8 months 6. Bone density scan (DEXA scan) of the lower spine and hip - baseline, 4 and 12 months 7. Magnetic resonance imaging (MRI) of the hips 8. Psychological evaluation and quality of life evaluation - baseline, 1, 2 and 8 months 9. Blood tests for adrenal gland function - baseline, 4 and 8 months 10. Blood and urine tests - 10, 12, 15, and 18 months Patients who achieve remission (whose urine protein levels decrease to normal) before completing the 8 months of dexamethasone will take one more dose and then stop therapy, but continue with follow-up. Patients who achieve remission but relapse may be offered a second course of treatment. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004990 •
Radiation Therapy and High-Dose Corticosteroids in Treating Older Patients With Primary CNS Non-Hodgkin's Lymphoma Condition(s): primary central nervous system lymphoma; intraocular lymphoma Study Status: This study is no longer recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with corticosteroids may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: Phase II trial to study the effectiveness of radiation therapy and high-dose corticosteroids in treating older patients with primary CNS non-Hodgkin's lymphoma. Phase(s): Phase II Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003278 •
Sex Steroid Hormones and Risk of CHD in Women Condition(s): Cardiovascular Diseases; Postmenopause; Coronary Arteriosclerosis
Heart
Diseases;
Coronary
Disease;
Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate the relationship between endogenous estrogen and androgen levels and risk of coronary heart disease among postmenopausal women in the Women's Health Initiative-Observational Study (WHI-OS). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006407 •
Solitary Islet Transplantation for Type 1 Diabetes Mellitus Using Steroid Sparing Immunosuppression Condition(s): Insulin Dependent Diabetes Mellitus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will test whether a new islet transplant procedure will enable patients with type 1 diabetes mellitus to stop insulin therapy. Islets are cell clusters in the pancreas that contain insulin-producing cells. The new procedure features three important advances, first developed by a group in Edmonton, Canada, over the way islet transplants have traditionally been performed: 1) the islets are transplanted immediately after they are removed from the donor; 2) islets are transplanted from two different donors in order to obtain the number of islets in a normal pancreas; and 3) the anti-rejection drug regimen is designed to reduce the harmful side effects of "conditioning" chemotherapy. (In the standard transplant procedure, patients receive intensive chemotherapy following the transplant. This study will use no radiation and lower-dose chemotherapy.) Patients between the ages of 18 and 65 with the diagnosis of type 1 diabetes mellitus for at least 5 years may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, chest Xray and tuberculin skin test, electrocardiogram and exercise test for heart function, abdominal ultrasound, psychological evaluation, and an arginine stimulated c-peptide test. The latter test determines if the patient is producing any insulin. Eligibility is restricted to patients who make no insulin at all. The study has an active phase lasting 15 months and follow-up that continues indefinitely. Patients will receive 10,000 "islet equivalents" per kilogram (2.2 pounds) of body weight. This will likely require two separate transplant procedures from two donors. Before the first surgery, patients will be given anti-rejection (immune suppressing) drugs, including FK506 and rapamycin (orally) and daclizumab (intravenously). The islets will be infused through a tube placed in the portal vein (the large vein that feeds the liver). After surgery, patients will receive insulin intravenously for 24 hours. They will then have an abdominal ultrasound and blood tests to determine liver function. If fewer than 10,000 islets were transplanted, patients will continue insulin treatment, with the dosages adjusted to account for the transplanted islets. They will take Daclizumab every 2 weeks, and FK506 and rapamycin
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daily. Blood tests to follow how much of these drugs are in the blood stream will be performed daily at first and then weekly after blood levels of these drugs stabilize. They will be given antibiotics to prevent infections. The arginine test will be repeated 2 weeks after the transplant and periodically thereafter. Blood will be drawn weekly to check drug levels, and monthly for other tests. The investigators will track daily insulin requirements, and these will be recorded monthly. Patients who require a second transplant to achieve the required amount of islets will return for the procedure when a compatible organ is donated. The second procedure will be done as described above. As before, insulin will be infused for 24 hours following surgery. It will then be stopped, however, and will not be resumed unless blood glucose levels reach above 180 milligrams/deciliter. Patients will continue taking FK506 and rapamycin indefinitely. Daclizumab will be given every 2 weeks for 4 doses following the second transplant, and then stopped. Patients will take an antiviral called ganciclovir for 14 weeks and another antibiotic for 1 year following surgery. For the first year after surgery, patients will have frequent blood tests to monitor drug levels and immune function. They will return to NIH for a complete history and physical examination 2 and 3 years after the final islet transplant and will be contacted yearly by phone to ascertain their general health status and whether they remain insulin independent. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006505 •
Steroids and Methotrexate to Treat Systemic Vasculitis Condition(s): Inflammation; Vasculitis; Wegener's Granulomatosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of prednisone and methotrexate in treating severe Wegener's granulomatosis and other systemic vasculitides. These diseases involve inflammation of blood vessels (vasculitis) that may affect the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart and other sites. Current treatment with prednisone and the anti-cancer drug cyclophosphamide is effective, but has significant side effects and a high rate of disease recurrence. In a small number of patients with vasculitis, prednisone and methotrexate, another anti-cancer drug, have led to marked improvement, with fewer side effects than are seen with cyclophosphamide. This study will evaluate this drug combination in a larger patient population. Patients 10 to 80 years of age with active Wegener's granulomatosis, polyarteritis nodosa, Churg-Strauss vasculitis, or microscopic polyangiitis overlap may be eligible for this 2 1/2 to 3-year study. In addition, patients with glomerulonephritis (a type of kidney disease) and a positive blood test for CANCA (antibodies found in certain vasculitic kidney diseases) or inflammatory sinusitis or lung nodule or infiltrates in the absence of infection may also be enrolled. Participants will take prednisone daily, by mouth, and low-dose methotrexate weekly, by mouth or by injection either under the skin, into a muscle or into a vein. Patients who significantly improve with treatment will gradually reduce, and eventually stop, the prednisone. If the remission lasts, methotrexate will also be reduced and stopped after 2 1/2 years. If active disease recurs, the original treatment program may be started again. Patients who never achieve complete remission with treatment but whose symptoms are well
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controlled and experience no serious side effects may choose to either continue low-dose methotrexate or stop therapy. Patients will be hospitalized 4 to 6 times a year, about 2 to 8 days each time, depending on their disease severity and response to illness. In addition, they will have the following tests and procedures: - Medical history and physical examination (upon admission to the study and then every 1 to 3 months). Blood tests for blood cell counts and for levels of enzymes that indicate liver damage (upon admission, then weekly, and finally, no less than monthly). - Additional blood tests to measure blood chemistries and evaluate kidney function (upon admission and again when clinically indicated). - Chest X-rays (upon admission and when clinically indicated). - Computerized tomography (CT) and magnetic resonance imaging (as needed). - Electrocardiogram (upon admission and then as clinically indicated). - Lung function studies (upon admission and at least every 6 months or as clinically indicated). - Ear, nose and throat evaluations (as clinically indicated). - Liver biopsy, if blood tests to monitor liver function are persistently abnormal. This procedure is done in the hospital under sedation to induce relaxation and drowsiness. The skin over the liver (upper right abdomen) is numbed with a local anesthetic and a needle is passed rapidly in and out of the liver to collect a small tissue sample for microscopic examination. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001256 •
A Trial of Two Steroid Treatments in Premature Infants Condition(s): Infant, Low Birth Weight; Respiratory Distress Syndrome; Respiratory Insufficiency Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Infants who are on breathing support are often treated with steroids (dexamethasone); however, the best timing of therapy is not known. This trial looked at the benefits and hazards of starting dexamethasone therapy at two weeks of age and four weeks of age in premature infants. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011362
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Islet Cell Transplantation Alone and CD34+ Enriched Bone Marrow Cell Infusion in Patients with Diabetes Mellitus: Steroid-Free Regimen Condition(s): Type 1 Diabetes Mellitus Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The goal of islet cell transplantation in Type 1 diabetics is to provide those affected with constant normal blood glucose levels, thereby reducing or eliminating altogether the need for injected insulin. This normalization may prevent or slow progression of diabetic complications, result in a healthier lifestyle, and lead to a
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better quality of life. Participants who meet the inclusion criteria will undergo an extensive screening process which typically includes a series of blood tests, EKG, chest x-rays, and a psychological evaluation, among others. Those who are eligible for and chose to participate in the trial will receive an islet cell transplant and bone marrow infusion from the same donor, together with following immunosuppressive medications: tacrolimus, sirolimus, daclizumab and infliximab. Because the bone marrow infusion may successfully prevent the transplanted islet cells from rejecting, some participants may be able to stop taking the immunosuppressive medications after a year. The islet cell transplant is done under local anesthesia in a special procedure radiology room. Several days after the islet cell transplant, the participant is admitted to the hospital as an outpatient in order to receive bone marrow via a simple intra-venous infusion procedure. All participants will need to be seen at the Diabetes Research Institute after the transplant for follow-up testing and post-islet cell transplant care. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021801 •
Islet Cell Transplantation Alone in Patients with Type I Diabetes Mellitus: steroidfree immunosuppression Condition(s): Diabetes Mellitus, Type 1 Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The goal of islet cell transplantation in patients with Type 1 Diabetes Mellitus is to provide constant normal blood glucose levels. This may eliminate the need for insulin altogether or provide a significant reduction in the amount of insulin necessary to maintain constant normal blood glucose levels. This normalization may prevent or slow progression of diabetic complications. Furthermore, the participant may enjoy a healthier lifestyle and a better quality of life. If you meet the initial inclusion criteria for the trial, you must be able to give informed consent personally. Then you will need to participate in an extensive screening process that involves many standard tests and collection of laboratory samples to make sure that the transplant is suitable and safe for you. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021788
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Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE) Condition(s): Bronchopulmonary Dysplasia; Respiratory Distress Syndrome; Infant, Premature, Diseases Study Status: This study is terminated. Sponsor(s): National Institute of Child Health and Human Development (NICHD)
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Purpose - Excerpt: Preterm birth is a common cause of neonatal morbidity and mortality, including chronic lung disease. Extremely premature newborns who required oxygen and a ventilator for lung disease were randomized to a low tapering dose of corticosteroids vs salt water AND minimal mechanical breathing support vs routine mechanical breathing support for 10 days to test whether either intervention would reduce the risk of death or lung problems. The infants' neurodevelopment will be evaluated at 18 to 22 months corrected age. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005777 •
Phase I/II trial rHuKFG for the Treatment of Steroid Refractory Gastrointestinal Acute GVHD Condition(s): Acute Graft Versus Host Disease Study Status: This study is terminated. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: Phase II efficacy evaluation, phase I/II efficacy and toxicity trial of recombinant human keratinocyte growth factor for the treatment of steroid refractory gastrointestinal graft versus host disease. Phase(s): Phase I; Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038792
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Pilot Study in Patients with Symptomatic Steroid-Naive Asthma Condition(s): Asthma Study Status: This study is completed. Sponsor(s): Protein Design Labs Purpose - Excerpt: The purpose of the study is to evaluate an investigational medication to treat chronic asthma. The research is being conducted at 20 clinical research sites in the US and is open to both men and women ages 18 to 70 years. Participants in the study will have a number of visits to a research site over an 8-month period. All study-related care and medication is provided to qualified participants at no cost. This includes all visits, examinations and laboratory work. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00024544
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Prevention of Neonatal Respiratory Distress Syndrome With Antenatal Steroid Administration Condition(s): Lung Diseases; Respiratory Distress Syndrome
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Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effect of corticosteroids, administered 24 to 48 hours before parturition, on the incidence of neonatal respiratory distress syndrome (RDS) and to determine whether the therapy has any adverse short- or long-term (up to 36 months) effects on the infant. Secondarily, to determine whether the therapy has any adverse short-term effects on the mother and to determine whether morbidity rates for neonatal respiratory distress syndrome as well as total and cause-specific infant mortality rates differ between mothers who received antenatal steroids and those who received conventional medical care. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000563 •
Prevention of Steroid-Induced Osteoporosis in Children Condition(s): Osteoporosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The purpose of this study is to determine whether the drug pamidronate can safely and effectively improve bone mineral density in growing children who have bone disease caused by taking steroid medications. People who take steroid medications called glucocorticoids, like prednisone or dexamethasone, for long periods almost always have decreased bone density and are at increased risk of breaking a bone. Research has shown that pamidronate improves bone density in adults who take glucocorticoids. However, use of pamidronate is not approved in children because it has not been extensively tested in children. It is possible that children will have a different response or unique problems with the medication because their bones are still growing. We will assign all study participants to one of two groups. One group will recieve pamidronate intravenously (through a vein) every 3 months in addition of daily oral calcium and vitamin D and the other group will receive calcium and vitamin D. The study is scheduled to run for 36 months, with visits to the study center once every 3 months. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022841
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Sex Steroids, Obesity and Lipids in Adolescent Females Condition(s): Cardiovascular Diseases; Heart Diseases; Obesity; Hypercholesterolemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To prospectively explore the relationships of endogenous sex steroid hormones and obesity and their interactions with lipoprotein cholesterol and
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apolipoprotein levels in nine and ten year old Black and white adolescent girls for five years during puberty. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005210 •
Steroid Hormones, TH1/TH2 Cytokines and Reproductive Status Condition(s): Arthritis, Rheumatoid; Healthy; Pregnancy Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study is designed to evaluate blood Th1 and Th2 immunoregulatory cytokine production and hormonal levels associated with the third trimester of pregnancy and the postpartum state. Cytokine and hormone levels will be assessed in blood specimens obtained from healthy pregnant and postpartum females and compared to levels from premenopausal non-pregnant and non-postpartum females. Blood samples obtained at 30-36 weeks of gestation and 2-6 weeks postpartum will be the primary study points. Samples will also be obtained from pregnant, postpartum, and non-pregnant, non-postpartum, premenopausal female patients with rheumatoid arthritis. Additional data will be generated from samples from normal males, which will be compared with data from females. We expect to find that pregnancy is associated with enhanced Th2 cytokine expression and that the postpartum state is associated with enhanced Th1 cytokine expression. We expect to see differences in cytokine expression between males and females as well. We seek to gather data supporting the view that distinct hormonal environments regulate these contrasting immunological states. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001376
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Study comparing ABX-CBL (monoclonal antibody) versus Atgam in Patients with Steroid Resistant Acute Graft versus Host Disease Condition(s): Graft vs Host Disease Study Status: This study is completed. Sponsor(s): Abgenix; Sangstat Medical Corporation Purpose - Excerpt: Trial evaluating the improvement in survival at 180 days of two therapies (Atgam versus ABX-CBL, a monoclonal antibody) in patients with acute graft versus host disease that does not respond to steroid therapy. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035880
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “steroids” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON STEROIDS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “steroids” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on steroids, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Steroids By performing a patent search focusing on steroids, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on steroids: •
.DELTA.16-20-Keto steroid conversion to 17.alpha.-hydroxy-20-keto steroids Inventor(s): Walker; Jerry A. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,568,492 Date filed: September 14, 1984 Abstract:.DELTA.16-20-keto steroids (I) are converted to 17.alpha.-hydroxy-20-keto steroids (III) in 2 steps, hydrosilylation followed by peracid oxidation. Excerpt(s): The transformation of a.DELTA.sup.5,16 -20-keto steroid to the corresponding 20-trimethylsilylenol ether by hydrosilylation is described in Helv. Chem. Acta 61, 3068 (1978). The hydrosilylation of enones with silanes in the presence of tris-(triphenylphosphine)rhodium (I) chloride catalyst is known where there is 1,4addition of the silane to the.alpha.,.beta.-unsaturated carboxy compound; see J. Organometallic Chemistry 94, 449 (1975). The oxidation of non-steroid silylenol ethers to the corresponding.alpha.-hydroxy ketones is discussed in Tetrahedron Letters 4319 (1974). Web site: http://www.delphion.com/details?pn=US04568492__
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.increment.sup.16 unsaturated C.sub.17 heterocyclic steroids useful as steroid C.sub.17-20 lyase inhibitors Inventor(s): Peet; Norton P. (Cincinnati, OH), Burkhart; Joseph P. (Plainfield, IN), Gates; Cynthia A. (Fairfield, OH) Assignee(s): Merrel Pharmaceuticals, Inc. (Bridgewater, NJ) Patent Number: 5,965,548 Date filed: May 6, 1998 Abstract: The present invention relates to.DELTA.sup.16 unsaturated steroids which are useful as steroid C.sub.17-20 lyase inhibitors. Excerpt(s): It is estimated that 75% of prostatic cancers are sensitive to levels of androgens, more specifically testosterone. (Van Wauwe, J. P. and Janssen, P. A. J., J. Med. Chem., (1989), 32, 2233). It is well established that reduction of serum testosterone levels is useful in the treatment of such prostatic cancers. In clinical practice, this has been accomplished for example by orchiectomy or by diethylstilbestrol treatment. However, the first approach is often psychologically unacceptable while a number of side effects are associated with the second approach. The cytochrome P450.sub.17.alpha. monooxygenase enzyme system catalyzes the 17.alpha.-hydroxylation of C.sub.21 steroids and also catalyzes the oxidative cleavage of the C.sub.17-20 bond. (Blohm, T. R. et al., Biochem. Biophys. Res. Commun., (1989), 162, 1571). More specifically the steroid C.sub.17-20 lyase activity of cytochrome P-450.sub.17.alpha. catalyzes the conversion of the C.sub.21 steroids pregnenolone and progesterone to the C.sub.19 steroids dehydroepiandrosterone and androstenedione, which are the precursors of the androgens, 5.alpha.-dihydrotestosterone and testosterone. Androstenedione and testosterone, in turn, are the Precursors of the estrogens, estrone
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and estradiol. Thus, inhibition of the steroid C.sub.17-20 a lyase can reduce formation of the androgens as well as the estrogens. As a result of this effect, the search for effective and selective inhibitors of the steroid C.sub.17-20 lyase enzyme is expanding. (Laughton, C. A. and Neidle, S., Biochem. Biophys. Res. Commun., (1990), 171, 1160). C.sub.17-20 lyase inhibitors would be useful for treating various androgen-dependent disorders. More particularly, such compounds would be useful in the treatment of prostatic-carcinoma, benign prostatic hyperplasia, male-pattern baldness and virilism and hirsutism (in women). In addition, C.sub.17-20 lyase inhibitors would also be useful in the treatment of estrogen-dependent disorders, such as estrogen dependent breast cancer. Thus, in light of the drawbacks associated with diethylstilbestrol treatment or orchiectomy, there has been an ongoing search for effective inhibitors of steroid C.sub.17-20 lyase. The present invention relates to C.sub.17 heterocyclic steroids and also to a method for using such compounds as effective steroid C.sub.17-20 lyase inhibitors. More particularly, the present invention relates to the treatment of androgen dependent disorders. Web site: http://www.delphion.com/details?pn=US05965548__ •
11.beta.-phenyl-14.beta.H steroids Inventor(s): Scholz; Stefan (Berlin, DE), Neef; Gunter (Berlin, DE), Ottow; Eckhard (Berlin, DE), Elger; Walter (Berlin, DE), Beier; Sybille (Berlin, DE), Chwalisz; Krzysztof (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin und Bergkamen, DE) Patent Number: 5,244,886 Date filed: March 20, 1991 Abstract: New 11.beta.-phenyl-14.beta.H-steroids of general formula (I), where Z is an oxygen atom or the hydroxyimino-grouping N.about.OH, and M and N are either jointly a second compound or L is a hydrogen atom and M is an.alpha.-permanent hydroxy group and either A and B together are a second compound and D is a hydrogen atom, where R.sup.1 is a five or six-part heteroalkyl residue or a cycloalkyl, cycloalkenyl or aryl residue or A is a hydrogen atom and B and D together are a methylene bridge, where R.sup.1 besides the aforementioned residues may be a possibly substituted hydrocarbon residue with up to 10 C atoms, a possibly substituted amino group, a hydroxy or C.sub.1-8 alkoxy, mercapto or thioalkyl group, R.sup.2 is a methyl or ethyl residue, and R.sup.3 /R.sup.4 represents the usual combination of substituents on the C17 atom in steroid chemistry, having antigestagenic and other properties. Excerpt(s): Q stands for an oxygen atom or two hydrogen atoms. As a special feature the compounds of this invention, deviating from naturally occurring steroids, exhibit a betaposition hydrogen atom on the 14 carbon atom. Such 14beta H steroids have already recently become known to a limited extent from European patent application 0 277 676. These known compounds with.DELTA.sup.4,9 -3-keto steroid skeleton exhibit in the 11 position a p-substituted (hetero)aryl ring. There are described as p-substituents: optionally saturated or unsaturated, straight-chain or branched hydrocarbon radicals with 1-10 carbon atoms, and the hydrocarbon radical additionally can also carry a hydroximino, oxo and/or hydroxy group of an amino group --NXY, with X and Y=H or C.sub.1 -C.sub.4 alkyl, and if X and Y=alkyl, these, together with N, can also form a heterocyclic 3- to 7-ring. The substitution pattern obtainable according to EP-A 0 277 676 on the 11beta phenyl ring is relatively limited. The search for other 14beta H steroids, which exhibit substituents on the 11beta phenyl ring exceeding EP-A 0 277 676, therefore
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seems urgently necessary to achieve compounds which, for example, with regard to their antigestagen action, are superior to those of EP-A 0 277 676. Web site: http://www.delphion.com/details?pn=US05244886__ •
11-Difluoromethylene steroids Inventor(s): Ayer; Donald E. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,567,000 Date filed: August 31, 1984 Abstract: 11-Difluoromethylene steroids having progestational and anti-progestational properties, useful as anti-fertility agents, are disclosed as well as a process for making the 11-difluoromethylene steroids. Excerpt(s): Steroids substituted in the C.sub.11 position with an unsaturated substituent are known. U.S. Pat. No. 3,927,046 discloses 11-methylene and 11-(alkyl substituted)methylene steroids, U.S. Pat. No. 4,292,251 discloses 11.beta.-substituted unsaturated aliphatic hydrocarbon substituents containing 2-3 carbon atoms. Neither of these patents discloses any halogen substitution. Difluoromethyl steroids are known with the difluoro substituent at C.sub.11, see U.S. patent application Ser. No. 639,285, filed Aug. 8, 1984 fee has been paid. Steroids containing a fluoromethylene group (.dbd.CHF) are known. (E)-11-fluoromethylene and (Z)-11-fluoromethylene steroids are known, see U.S. patent application Ser. No. 639,285, filed Aug. 8, 1984 for fee has been paid. Web site: http://www.delphion.com/details?pn=US04567000__
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11-Substituted steroids and intermediates Inventor(s): Johnson; William S. (Portola Valley, CA) Assignee(s): The Board of Trustees of Leland Stanford Junior University (Stanford, CA) Patent Number: 4,032,579 Date filed: April 28, 1975 Abstract: Precursor compounds are provided for use in the synthesis of 11chalcogensubstituted steroids and nor-steroids, particularly 18-, 19- and A-nor-steroids. The compounds are acyclic or substituted polyenine with the olefinic groups having the proper geometry to provide the natural ring fusions upon cyclization. To initiate cyclization, a chalcogen atom is positioned in relation to a double bond, so that on protonation of the chalcogen atom, the resulting carbocation will interact with the double bond to form a pi bond if the cyclization initiator is carbocyclic and a sigma bond if the cyclization initiator is acyclic. Upon cyclization, it is found that the substituent at C-11 of the resulting steroid is in the alpha position. Various methods are provided for producing the cyclization precursor. Excerpt(s): The primary starting material for commercially employed steroids are plant steroids. Since the plant steroids differ as to substituents on the ring and particularly as to the substituent at the C-17 position, substantial modification of the plant steroid is required. In addition, because one is concerned with a product which is susceptible to
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fluctuation and availability, there have been substantial efforts to find alternative means for preparing steroidal compounds. In synthesizing steroids from small readily available organic fragments, one must be concerned with the complex structure of the polycyclic steroid, as well as the particular geometry of the substituents and the ring fusions. In synthesizing a steroid, it is therefore necessary that one introduce the various substituents having the desired geometry and in preparing the rings, provide a means for obtaining the ring fusions having the specified geometry. Since the synthesis will invariably involve a number of steps, it is necessary during the synthetic sequence to insure that subsequent steps do not affect prior conformations which have been introduced so as to provide desired geometry. In addition, where catalyzed cyclization of a polyunsaturated compound is involved there must be concern about the effect of various substituents on the carbon atoms which will ultimately be annular carbon atoms. Since the cyclized compound will be more compact then the acyclic compound, non-bonded steric interactions can be expected to deleteriously affect the course of the cyclization. Where heteroatoms are present on the polyunsaturated chain, the inductive effect of the heteroatoms, their interaction with acid, and their ultimate geometry must be taken into account. In addition, the choice of the polyunsaturated compound must allow for cyclization to the steroidal structure without interruption, so that the tetracyclic compound is formed, rather than a lower order polycyclic compound. Novel cyclization precursor compounds are provided which are substituted with functionalized substituents at a carbon atom which serves as the C-11 position. The compounds are acyclic or substituted monocyclic compounds which are polyunsaturated. The C-11 carbon atom is substituted with a chalcoxy substituent. The cyclization precursor has a group which serves as an initiator of the cyclization upon acid catalysis, which has a chalcogen atom (oxygen or sulfur) in juxtaposition with a double bond, so that upon protonation of the chalcogen atom, there is interaction with the carbocation and double bond to form a new carbon-carbon bond. Methods are provided for preparing the cyclization precursor. Web site: http://www.delphion.com/details?pn=US04032579__ •
14.alpha.,17.alpha.-dihydroxy-17.beta.-substituted steroids Inventor(s): Smid; Peter M. (Bleiswijk, NL), Van Zoest; Willem J. (Schiedam, NL), Weber; Pieter G. (Delft, NL), Marx; Arthur F. (Delft, NL) Assignee(s): Akzo N.V. (Arnhem, NL) Patent Number: 5,093,502 Date filed: February 16, 1990 Abstract: A process for the preparation of novel 14.alpha., 17.alpha.-dihydroxy-17.beta.substituted steroids by reacting 14.alpha.-hydroxy-17-oxo-steroids with metal organic compounds and the use of the said novel steroids in the production of 14.alpha., 17.alpha.-methylenedioxy-pregnane derivatives. Excerpt(s): Steroids occur widely in nature, both in animals and plants. Many steroids are hormones such as estrogens and cortisone which are produced by the body's endocrine system and are of great importance in the regulation of numerous body processes such as growth and metabolism. Over the last 35 to 40 years, steroid therapy or the medical augmentation of steroid hormone insufficiencies in the body has been one of the major chapters in the history of medical progress. Steroids are used now as anti-inflammatory agents, anti-allergic agents, anabolic agents, diuretics and contraceptives among other uses. For a long time, steroids for medical use were
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prepared starting with the isolation of steroids from natural sources followed by partial chemical degradation and one or more chemical reactions to obtain the desired substituent pattern. The oldest examples of steroids isolated from natural sources, which are still important as starting material for the preparation of steroids for medical use, are cholesterol, lanosterol and cholic acids. Since then, hecogenin and diosgenin became important raw materials too. At the present time, cheap starting materials for the synthesis of pharmaceutically active steroids are available by microbiological degradation of natural steroids. Especially a number of 17-oxo-steroids can be made by degradation of the abundant soybean derived sterols, sitosterol and campesterol in this way. 17-oxo-steroids which may be prepared in this way are for instance.DELTA.sup.4 androstene-3,17-dione and.DELTA.sup.4 -androstadiene-3,17-dione which derivatives can be converted into other steroid compounds in a manner known in the art. Web site: http://www.delphion.com/details?pn=US05093502__ •
14-Functionalized 8,19-oxido steroids and processes for preparation thereof Inventor(s): Kruger; Gunther (St. Laurent, CA) Assignee(s): Steele Chemicals Co. Ltd. (Quebec, CA) Patent Number: 4,134,891 Date filed: August 2, 1976 Abstract: There are provided novel 14-functionalized 8,19-oxido steroids possessing 14.alpha. or 14.beta.-hydroxy, 14.alpha. and 14.beta.-acetoxy, 14.alpha.,15.alpha.-oxido or 14.beta.,15.beta.-oxido groups or a double bond in position 14 as well as processes for preparing such compounds. These compounds can be readily converted into the corresponding 14.beta.-hydroxycardenolides, 19-oxygenated cardenolides, 19norcardenolides and unsaturated cardenolides. Excerpt(s): This invention relates to steroid compounds. More particularly, one aspect of this invention relates to processes for the preparation of 14-functionalized 8,19-oxido steroids possessing 14.alpha. or 14.beta.-hydroxy, 14.alpha. and 14.beta.-acetoxy, 14.alpha.,15.alpha.-oxido or 14.beta.,15.beta.-oxido groups or a double bond in position 14. In a still further aspect of this invention, there are provided novel compounds of the type just mentioned, as described hereinafter in greater detail. In greater detail, and referring initially to process (a), the initial step of treating a compound of the Formula II with a peracid yields the mixture of 3-ketones of Formulae IIIa, IIIb and I as previously outlined. Amongst the solvents which may be used are those which include, for example, carbon tetrachloride, benzene, hexane, methanol, etc. Reaction temperatures may range from below to above room temperature as desired. The peracid employed in this reaction may be any suitable peracid for this purpose; typical examples being perbenzoic acid, metachloroperbenzoic acid, peracetic acid, etc. The resulting mixture of isomeric 8,14- and 8,19-oxides obtained may be separated and the isolated 8,14-oxides may then be treated with an acid to form the 14.alpha. and.beta. -hydroxy compounds of Formula I. The optional reduction of the 3-ketones of Formulae IIIa or IIIb to the 3alcohols IIIa or IIIb, respectively, may be carried out conventionally using a metal hydride in a suitable solvent, e.g. sodium borohydride in methanol. In carrying out the acid treatment step, a suitable carboxylic acid is preferably employed, such as, e.g. acetic acid, propionic acid, benzoic acid, etc. Alternately a dilute aqueous mineral acid may be employed. The acid treatment is carried out at temperatures ranging from 0.degree. to 100.degree. C. In the case of 8.beta.,14.beta.-oxido-4,6-dien-3-ones are reacted with a carboxylic acid the acid treatment is preferably carried out at elevated temperatures, e.g.
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at 70.degree. in all other cases it is carried out preferably at room temperature or below. If desired, a solvent may be employed if the particular acid used in the acid treatment is not a solvent per se; such additional solvents being, for example, carbon tetrachloride, ethyl acetate, benzene, toluene, etc. Web site: http://www.delphion.com/details?pn=US04134891__ •
16 unsaturated C17 heterocyclic steroids useful as steroid C17-20 lyase inhibitors Inventor(s): Peet; Norton P. (Cincinnati, OH), Burkhart; Joseph P. (Plainfield, IN), Gates; Cynthia A. (Fairfield, OH) Assignee(s): Merrell Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 5,677,293 Date filed: July 15, 1996 Abstract: The present invention relates to.DELTA.sup.16 unsaturated C.sub.17 heterocyclic steroids which are useful as steroid C.sub.17-20 lyase inhibitors. Excerpt(s): It is estimated that 75% of prostatic cancers are sensitive to levels of androgens, more specifically testosterone. (Van Wauwe, J. P. and Janssen, P. A. J., J. Med. Chem., (1989), 32, 2233). It is well established that reduction of serum testosterone levels is useful in the treatment of such prostatic cancers. In clinical practice, this has been accomplished for example by orchiectomy or by diethylstilbestrol treatment. However, the first approach is often psychologically unacceptable while a number of side effects are associated with the second approach. The cytochrome P4501.sub.17.alpha. monooxygenase enzyme system catalyzes the 17.alpha.hydroxylation of C.sub.21 steroids and also catalyzes the oxidative cleavage of the C.sub.17-20 bond. (Blohm, T. R. et al., Biochem. Biophys. Res. Commun., (1989), 162, 1571). More specifically the steroid C.sub.17-20 lyase activity of cytochrome P450.sub.17.alpha. catalyzes the conversion of the C.sub.21 steroids pregnenolone and progesterone to the C.sub.19 steroids dehydroepiandrosterone and androstenedione, which are the precursors of the androgens, 5.alpha.-dihydrotestosterone and testosterone. Androstenedione and testosterone, in turn, are the precursors of the estrogens, estrone and estradiol. Thus, inhibition of the steroid C.sub.17-20 lyase can reduce formation of the androgens as well as the estrogens. As a result of this effect, the search for effective and selective inhibitors of the steroid C.sub.17-20 lyase enzyme is expanding. (Laughton, C. A. and Neidle, S., Biochem. Biophys. Res. Commun., (1990), 171, 1160). C.sub.17-20 lyase inhibitors would be useful for treating various androgendependent disorders. More particularly, such compounds would be useful in the treatment of prostatic carcinoma, benign prostatic hyperplasia, male-pattern baldness and virilism and hirsutism (in women). In addition, C.sub.17-20 lyase inhibitors would also be useful in the treatment of estrogen-dependent disorders, such as estrogen dependent breast cancer. Thus, in light of the drawbacks associated with diethylstilbestrol treatment or orchiectomy, there has been an ongoing search for effective inhibitors of steroid C.sub.17-20 lyase. The present invention relates to C.sub.17 heterocyclic steroids and also to a method for using such compounds as effective steroid C.sub.17-20 lyase inhibitors. More particularly, the present invention relates to the treatment of androgen dependent disorders. Web site: http://www.delphion.com/details?pn=US05677293__
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17.beta.-Difluoromethyl steroids Inventor(s): Campbell; J. Allan (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,416,822 Date filed: July 9, 1982 Abstract: 17.beta.-Difluoromethyl steroids are disclosed which have progestational, antiprogestational activity and which are useful as and male and female contraceptive agents. Excerpt(s): The process of transforming a 17-keto steroid to the corresponding steroid with an aldehyde at C.sub.17 by addition of a carbon atom is known to those skilled in the art. See, for example, C. Byon et al. in J. Org. Chem. 45, 4404 (1980) and references therein; Chem. Abst. 85, 124237g; and East German Pat. No. 117,673. Aldehydes can be transformed to the corresponding difluoromethyl compound by reaction with selenium tetrafluoride, see Olah et al., J. Am. Chem. Soc. 96, 925 (1974), with sulfur tetrafluoride, see Martin and Kagan, J. Org. Chem. 27, 3164 (1962), or with diethylaminosulfur trifluoride, see Fieser and Fieser, Reagents for Organic Synthesis, Wiley Interscience, Vol. 6, p. 183 and Vol. 8, p. 166. 17,17-Difluoroandrost-4-en-3-one and 20,20difluoroprogesterone are known, see Martin, supra. The 20,20difluoromethylprogesterone of Martin was disclosed to possess central nervous system depressant activity which made the agents useful as sedatives and general anesthetics in mammals. U.S. Pat. No. 3,211,723 discloses that 20,20-difluoropregnane-11-one exhibits activity as an anti-fertility agent and can be used in controlling fertility in ovulating mammals and birds, for example, in animals such as swine, cattle, horses, sheep, dogs, cats and the like. Web site: http://www.delphion.com/details?pn=US04416822__
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19-nor-cholane steroids as neurochemical initiators of change in human hypothalamic function Inventor(s): Jennings-White; Clive L. (Salt Lake City, UT), Berliner; David L. (Atherton, CA), Adams; Nathan W. (Salt Lake City, UT) Assignee(s): Pherin Corporation (Mountain View, CA) Patent Number: 6,437,156 Date filed: February 2, 1999 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human vomeropherin, e.g. a 19-nor cholane steroid, or a pharmaceutical composition containing a vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): This invention relates generally to pharmaceutical compositions and methods for effectuating change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals. More particularly, the invention relates to the use of 19-nor-cholane steroids as neurochemical effectuators of physiology and behavior. The present invention relates to certain
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compounds, namely 19-nor-cholane steroids, particularly 19-nor-cholane steroids and related compounds as will be described herein, and methods of using these compounds as human vomeropherins in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g., the reduction of anxiety. The 19-norcholane steroids are characterized by a four ring steroidal structure, methylation at the 13 position and alkylation (C4) at the 17-position. The 19-nor-cholenes are a subset which have at least one double bond. Ohloff, G. et al. (Helv. Chim. Acta (1983) 66:192217), which is incorporated herein by reference, have shown that several steroids (androstenes) have an odor which varies with different isomeric, diastereomeric, and enantiomeric forms. Some members of this group have been reported to act as a pheromone in some mammalian species for instance, 5.alpha.-androst-16-en-3-one and 5.alpha.-androst-16-en-3.alpha.-ol in pigs (Melrose, D. R., et al., Br. vet. J. (1971) 127:497502). These 16-androstenes produced by the boar induce mating behavior in estrus sows (Claus, et al., Experimentia (1979) 35:1674-1675). Web site: http://www.delphion.com/details?pn=US06437156__ •
1-Oxygenated steroids Inventor(s): Wachter; Michael P. (Bloomsbury, NJ), Settepani; Joseph A. (Vienna, VA) Assignee(s): Ortho Pharmaceutical Corporation (Raritan, NJ) Patent Number: 4,096,253 Date filed: July 6, 1976 Abstract: 1-Oxygenated steroids and a method of preparing same as described. The 1oxygenated steroids are useful as antifertility agents. Excerpt(s): This invention relates to certain 1-oxygenated steroids which are active antifertility agents. The compounds exhibit anti-implantive activity and are useful in the suppression of reproduction in female animals. The 1-oxygenated steroids which are the subject of this invention are prepared by reacting an appropriately substituted estratriene derivative with a suitable reagent to form the desired compound. Those compounds having a trialkylaminosulfoxy group in the 1 or 3 position are prepared by reacting an appropriately substituted 1- or 3-hydroxyestratriene-17-one with an appropriate trialkylamine complex such as, for example, sulfur trioxide triethylamine complex, in a suitable base such as anhydrous pyridine. Those compounds wherein R.sub.1 or R.sub.2 is lower alkyl can be prepared by reacting an appropriately substituted 1-oxygenated-3-hydroxyestra-1,3,5(10)-trien-17-one, for example, with a suitable alkylating agent such as, for example, diazomethane, dimethyl sulfate, methyl iodide, butyl bromide and the like. Those compounds wherein R.sub.3 or R.sub.5 is hydroxy can be prepared by reduction of a suitably substituted 1-oxygenated estra1,3,5(10)-trien-17-one. Reducing agents which may be employed include platinum oxide, palladium and sodium borohydride. Those compounds containing a double bond at the 16-17 position can be prepared, for example, by reacting an appropriately substituted 17-keto derivative with an alkyl ester such as isopropenyl acetate at elevated temperatures. Those compounds wherein R.sub.3 is oxo and R.sub.4 is halogen can be prepared by reacting an appropriately substituted 1-oxygenated steroid having a double bond in the 16-17 position with a halogen. Those compounds wherein R.sub.5 is trifluoroalkanoyloxy can be prepared by reacting an appropriately substituted 1oxygenated-estra-1,3,5(10) -trien-17.beta.-ol with an appropriate anhydride such as, for example, trifluoroacetic anhydride. Those compounds wherein R.sub.5 is cyanoethoxy are prepared by reacting an appropriately substituted 17-hydroxy-1,3,5(10)-estratriene
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with an appropriate nitrile such as, for example, acrylonitrile in the presence of a base. Those compounds having an epoxide ring at the 16-17 position can be prepared by reacting an appropriately substituted 1-oxygenated compound which is unsaturated at the 16-17 position with a peracid such as, for example, perbenzoic acid. Web site: http://www.delphion.com/details?pn=US04096253__ •
2,19-methyleneoxy and 2,19-methylenethio bridged steroids as aromatase, 19hydroxylaser inhibitors and methods of their use in the treatment of estrogen mediated disorders Inventor(s): Peet; Norton P. (Cincinnati, OH), Johnston; J. O'Neal (Milford, OH), Burkhart; Joseph P. (West Chester, OH) Assignee(s): Merrell Dow Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 5,491,136 Date filed: March 18, 1994 Abstract: The present invention is directed to a method of using a certain compounds which are 2,19-methyleneoxy or 2,19 methylenethio bridged steroids, and related steroidal compounds as inhibitors of the enzyme steroid aromarase, 19-hydroxylase and as treatment for various estrogen dependent/mediated disorders including hormonal dependent breast cancer. Excerpt(s): The estrogen hormones, estrone and esitradiol, are involved in many physiological processes. The formation of these steroids is regulated by a number of enzymes. The enzyme aromatase is the rate limiting enzyme in the non-reversible conversion of the androgen hormones, testosterone and androstenedione, to the estrogen hormones, estradiol and estrone. Compounds such as aromarase inhibitors may thus regulate or inhibit androgen to estrogen conversion, and have therapeutic utility in treating clinical conditions potentiated by the presence of estrogens. 19Nordeoxycorticosterone (19-norDOC) is known to induce mineralocorticoid hypertension. In the biosynthetic formation of 19-norsteroids, such as 19-norDOC, the initial step is the adrenal hydroxylation of an appropriate steroid such as deoxycorticosterone (DOC). The inhibition of the biosynthetic formation of 19-norDOC by inhibition of 19-hydroxylation of DOC would thus serve to decrease the level of 19norDOC present in the animal involved and reduce hypertensive effects tributable to the presence of this material. Y is H, --OH, or --O--(C.sub.1-4 alkanoyl), and when Y.dbd.H, OH, or --O--(C.sub.1-4 alkanoyl), X may not include --OH, and R may not include.dbd.O or --OH. Web site: http://www.delphion.com/details?pn=US05491136__
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4,5-Seco-steroids Inventor(s): Cimarusti; Christopher M. (Hamilton, NJ), Levine; Seymour D. (North Brunswick, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (Princeton, NJ) Patent Number: 4,127,589 Date filed: February 6, 1975 Abstract: Novel 4,5-seco-steroids having anti-inflammatory activity are disclosed herein.
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Excerpt(s): Y can be hydrogen and Y' can be hydroxyl or together Y and Y' can be.dbd.O. The expression "lower alkyl" refers to both straight and branched chain alkyl groups having 1 to 7 carbon atoms; e.g., methyl, ethyl, propyl, isopropyl, t-butyl, heptyl, etc. Alkyl groups having 1 to 3 carbon atoms are preferred. The term "aryl" refers to a monoor bi-carbocyclic aromatic ring system having 6 or 10 carbon atoms; e.g., phenyl or naphthyl. Phenyl or phenyl substituted with halogen (fluorine, chlorine, bromine or iodine), lower alkyl, or lower alkoxy (having 1 to 7 carbon atoms) is preferred. Phenyl is the most preferred aryl group. Web site: http://www.delphion.com/details?pn=US04127589__ •
4,6,8(14)-Triene steroids Inventor(s): Kruger; Gunther (St. Laurent, CA) Assignee(s): Steele Chemicals Co. Ltd. (Pointe Claire, CA) Patent Number: 4,058,539 Date filed: June 16, 1976 Abstract: There are provided novel 4,6,8(14)-triene-steroids as well as processes for preparing such compounds. The above compounds are useful as intermediates in the preparation of other steroids, which in turn, may be converted into valuable pharmaceutical agents. Excerpt(s): This invention relates to steroid compounds. More particularly, one aspect of this invention relates to novel processes for preparing compounds of Formula (I). According to a still further aspect of the present invention, there are provided novel chemical compounds of the formula (Ia) useful as intermediates in the preparation of other compounds which may, in turn, be used as valuable starting materials for the production of pharmaceutically active compounds. From the literature, it is reported in the J.O.C. (J. Elks) 468 (1954) and from J.C.S. (P. Bladon) 2176 (1955) and as well J.C.S. (P. Bladon and T. Sleigh) 6991 (1965), and in addition from J.O.C. (W. F. Johns) 31, 3780 (1966), that certain 10.alpha.- and 10.beta.-methyl- as well as 10.beta.-hydrogen steroids can be converted to the corresponding 4,6,8 (14) -trien-3-ones. The methods used to employ such triene compounds involve long and complicated chemical reaction routes and result in low yields of the end products. In addition, certain of those techniques employ starting materials which are not readily available. Web site: http://www.delphion.com/details?pn=US04058539__
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4-amino-.DELTA.4-steroids and their use as 5.alpha.-reductase inhibitors Inventor(s): Weintraub; Philip M. (Cincinnati, OH), Burkhart; Joseph P. (West Chester, OH), Blohm; Thomas R. (Madeira, OH) Assignee(s): Merrell Dow Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 5,318,961 Date filed: December 20, 1992 Abstract: The present invention relates to 4-amino-.DELTA.sup.4 -steroids which are inhibitors of 5.alpha.-reductase. The compounds are useful for treating DHT-mediated diseases.
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Excerpt(s): Mammalian steroid 5.alpha.-reductase, an enzyme present in mammalian tissues including skin, male genitalia and prostate gland, catalyzes the conversion of the steroidal hormone testosterone to the steroidal hormone dihydrotestosterone (17.beta.hydroxy-5.alpha.-androstan-3-one). Testosterone and dihydrotestosterone (DHT) are both androgenic hormones and they are the primary androgenic steroids in males. These steroids are responsible for the physical characteristics which differentiate males from females. DHT, however, is much more potent than testosterone as an androgen and it acts as an end-organ effector in certain tissues, particularly in mediating growth. Furthermore, the formation of DHT occurs primarily in the target cells themselves as a result of the reduction of testosterone by 5.alpha.-reductase. It is known that skin responds to androgens and is an active site of androgen metabolism. In particular, testosterone is converted to DHT in the skin by the action of 5.alpha.-reductase. Testosterone metabolism in the skin may at times be abnormally excessive and have undesirable effects as a result of the DHT formed. Thus, there is considerable evidence that DHT is involved in the pathogenesis of acne, including acne vulgaris, as well as other androgen associated conditions [See Price, Arch. Dermatol. 111, 1496 (1975)]. Agents which are capable of blocking the formation of DHT from testosterone in skin, such as by inhibiting the activity of 5.alpha.-reductase, would therefore be useful in the treatment of acne. In addition, other physical conditions and disease states, including benign prostatic hypertrophy, androgenic alopecia (common baldness caused by androgen in genetically susceptible men and women), seborrhea and female hirsutism, are also associated with elevated androgen activity and could be treated by the administration of 5.alpha.-reductase inhibitors. [See T. Liang et al., Endocrinology 117, 571 (1985); J. R. Brooks et al., Steroids 47, 1 (1986); J. R. Carlin et al., Journal of Chromatography, 427, 79 (1988).] Thus, agents which are capable of blocking the formation of DHT from testosterone by inhibiting the effects of 5.alpha.-reductase would also be effective in the treatment of these conditions. Web site: http://www.delphion.com/details?pn=US05318961__ •
4-Halo steroids Inventor(s): Alvarez; Francisco S. (Sunnyvale, CA) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA) Patent Number: 4,273,770 Date filed: August 20, 1979 Abstract: Certain pregn-4-ene-3,20-diones or pregn-1,4-diene-3,20-diones 4-substituted with a fluoro or chloro are useful as topical anti-inflammatory steroids. These compounds are substituted at 9.alpha. with hydrogen, fluoro, chloro or bromo; at 6.alpha. with hydrogen, fluoro or chloro; at the 11 position with a keto, a.beta.-hydroxy or a.beta.-chloro (the latter only when there is a 9.alpha.-chloro); at 16.alpha., 17.alpha.positions with isopropylidenedioxy or at 16.alpha.- (or 16.beta.) with methyl when 17.alpha. is hydroxy (or an ester); and at the 21-position with mono-fluoro, chloro, bromo, hydroxy or alkanoyloxy of 2-6 carbons or difluoro, dichloro, dihydroxy or dimethoxy. Excerpt(s): This invention relates to novel corticosteroids. More specifically it relates to pregn-4-enes which are substituted at the 4 position with fluoro or chloro and are optionally substituted at C-6 with fluoro or chloro. The compounds are topically active anti-inflammatory agents in mammals. The invention further relates to pharmaceutically active compositions comprising the compound of the invention in
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combination with at least one pharmaceutically acceptable excipient. 4Chlorohydrocortisone and 4-fluorohydrocortisone are known compounds. However, no biological activity is shown for these compounds. See Ernst Jucher, Process in Drug Research, Vol. 5, p. 50, Birkhauser Verlag Basel and Stuttart, 1963. Other chemically related compounds are disclosed in U.S. Pat. No. 2,714,601 to Fonken et al. U.S. Pat. No. 3,127,424 to Adams et al; and U.S. Pat. No. 3,129,219 to Goly as being useful as intermediates. U.S. Pat. No. 3,232,960 to Magerlein et al discloses certain 4-fluoro-4pregnenes which may also have double bonds at C-1 and C-6 which are useful as antiinflammatories. U.S. Pat. No. 3,707,537 to Kierstead discloses certain 4-chloro-6-halopregna-4,6-dienes which require the presence of a 6-7 double bond. Another patent which discloses the possibility of certain 4,6-dihalo-pregna-4-enes is U.S. Pat. No. 3,489,748 to Benningen and Muller. These compounds differ from the compounds of this invention in that the Benningen et al compounds exhibit a 16.alpha.-alkylthio group and have no substitution at the 17.alpha. position. Furthermore, there are no di-substituted compounds disclosed, only 4-chloro-pregna-4,6,16-triene-3,20-dione and the corresponding 16.alpha.-ethylthiopregna-4,6-diene. Web site: http://www.delphion.com/details?pn=US04273770__ •
6,7-oxygenated steroids and uses related thereto Inventor(s): Burgoyne; David L. (Delta, CA), Shen; Yaping (Port Coquitlam, CA), Langlands; John M. (Richmond, CA), Rogers; Christine (Vancouver, CA), Chau; Joseph H.-L. (Vancouver, CA), Piers; Edward (Richmond, CA), Salari; Hassan (Tswassen, CA) Assignee(s): Inflazyme Pharmaceuticals Ltd. (Richmond, CA), The University of British Columbia (Vancouver, CA), The University of Alberta (Alberta, CA) Patent Number: 6,046,185 Date filed: July 10, 1997 Abstract: Steroid compounds having various oxygen substitution on the steroid nucleus are disclosed. A specific functionality present on many of the steroid compounds is oxygen substitution at both of positions 6 and 7. Thus, certain steroids have oxygen substitution at C6 and C7, and some have specific stereochemistries such as 6.alpha. and 7.beta. oxygen substitution, and an alpha hydrogen at the 5 position in addition to having 6.alpha. and 7.beta. oxygen substitution. Steroids having 3,4-epoxy functionality are also disclosed. In addition, steroids having C17 pyran and.delta.-lactone functionality, with oxygen substitution at C6 and C7, or at C15, of the steroid nucleus, are disclosed. Excerpt(s): The invention is directed to steroid compounds, and in particular to 6,7oxygenated steroid compounds and therapeutic uses related thereto. Asthma and allergy are closely related with good evidence from clinical studies demonstrating a strong correlation between the severity of asthma and the degree of atopy (allergy). Sensitization to allergens is believed to be the most important risk factor for asthma in both children and adults, with approximately 90% of asthma cases exhibiting atopy. Allergy is characterized by an increased blood serum IgE (antibody) level. Repeated exposure to allergens, in a process called sensitization, is normally required to elicit sufficient B cell production of IgE specific to a given allergen or series of allergens to trigger atopy and the subsequent asthmatic or allergic response. Once B cells are exposed to allergens, they produce antibodies which bind to the surface of mast cells. The crosslinking of 2 antibodies by the antigen causes a series of reactions causing degranulation and the release of a number of mediators which modulate the
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inflammatory response. Mediators that are released or generated during the asthmatic and allergic response include histamine, leukotrienes, prostaglandins, cytokines and tryptase. Web site: http://www.delphion.com/details?pn=US06046185__ •
7-Oxa steroids Inventor(s): Guthrie; Robert William (Fairfield, NJ), Kierstead; Richard Wightman (North Caldwell, NJ), Lemahieu; Ronald Andrew (North Caldwell, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 3,962,275 Date filed: December 11, 1974 Abstract: 7-Oxa steroids which may be substituted in the 3-position with a hydroxy oxo group or in the 2-position with a hydroxymethylene group or in the 2- and positions with a substituent that forms a 5-membered heterocyclic ring, useful antigonadotropic agents and a method of preparing these 7-oxa steroids from hydroxy.DELTA.sup.5 -steroids including intermediates in this process.
or 3as 3-
Excerpt(s): Are useful as antigonadotropic agents. Wherein R.sub.4 is a hydrolyzable ester, R' is acetyl or a hydrolyzable ester; R.sub.1 ' is hydrogen, lower alkyl or a hydrolyzable ester with the proviso that at least one of R' and R.sub.1 ' is other than a hydrolyzable ester. The term "conventional hydrolyzable ester" as used herein denotes the hydrolyzable ester group conventionally employed in the steroid art to protect hydroxy groups. Among the preferred esters are those from hydrocarbon carboxylic acids or phosphoric acids and their salts. The term "hydrocarbon carboxylic acids" defines both substituted and unsubstituted hydrocarbon carboxylic acids. These acids can be completely saturated or possess varying degrees of unsaturation (including aromatic), can be of straight chain, branched chain, or cyclic structure, and preferably contain from 1 to 12 carbon atoms. In addition, they can be substituted by functional groups, for example, hydroxy, alkoxy containing up to 6 carbon atoms, acyloxy containing up to 12 carbon atoms, nitro, amino, halogeno, and the like, attached to the hydrocarbon backbone chain. Typical conventional hydrolyzable esters thus included within the scope of the term and the instant invention are acetate, propionate, butyrate, valerate, caproate, enanthate, caprylate, pelargonate, acrylate, undecenoate, phenoxyacetate, benzoate, phenylacetate, diphenylacetate, diethylacetate, trimethylacetate, t-butylacetate, trimethylhexanoate, methylneopentylacetate, cyclohexylacetate, cyclopentylpropionate, adamantoate, glycolate, methoxyacetate, hemisuccinate, hemiadipate, hemi-.beta.,.beta.-dimethylglutarate, acetoxyacetate, 2chloro-4-nitrobenzoate, aminoacetate, diethylaminoacetate, piperidinoacetate,.beta.chloropropionate, trichloroacetate,.beta.-chlorobutyrate, dihydrogen phosphate, dibenzyl phosphate, benzyl hydrogen phosphate, sodium benzyl phosphate, cyclohexylammonium benzyl phosphate, sodium phenyl phosphate, sodium ethyl phosphate, di-p-nitrobenzyl phosphate, sodium o-methoxyphenyl phosphate, cyclohexylammonium p-cyanobenzyl phosphate, sodium phenacyl phosphate, benzyl ocarbomethoxyphenyl phosphate and the like. Web site: http://www.delphion.com/details?pn=US03962275__
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9.alpha.-hydroxy-17-methylene steroids, process for their preparation and their use in the preparation of corticosteroids Inventor(s): Batisi; Jacobus N. M. (Kwintsheul, NL), Marx; Arthur F. (Delft, NL) Assignee(s): Gist-Brocades N.V. (Delft, NL) Patent Number: 5,194,602 Date filed: December 12, 1990 Abstract: New 9.alpha.-hydroxy-17-methylene steroids are prepared by the introduction of a substituted 17-methylene group in 9.alpha.-hydroxyandrost-4-ene-3, 17-dione.The resulting compounds are useful starting compounds in the synthesis of corticosteroids. Excerpt(s): The invention relates to new 9.alpha.-hydroxy-17-methylene steroids with a substituted 17-methylene group, to their preparation and to their use in the preparation of corticosteroids. Nearly all steroids which are currently used as pharmaceuticals originate either directly or indirectly from steroid raw materials found in nature. Originally diosgenin formed the main supply of a raw material. In order to become less dependent of this specific compound investigations have been made to see if other steroids which are abundantly available, e.g. cholesterol, sitosterol, stigmasterol or campesterol could also be used as a starting substance. Microbiological processes were developed to convert in one step said substances into 17-oxo steroids, especially into androst-4-ene-3,17-dione. From the latter compound it was possible to obtain 9.alpha.hydroxyandrost-4-ene-3,17-dione using a second microbiological step. This compound can be prepared even directly from the above-mentioned sterols, for example by using a specific Mycobacterium fortuitum strain, see British patent No. GB-A-1530730, or Mycobacterium species, CBS 482.86, see European patent application No. 87202619.0. For several syntheses which lead to pharmacologically active steroids 9.alpha.hydroxyandrost-4-ene-3,17-dione is a very suitable starting compound, because it is apt to functionalisation in the D-ring, as well as in the C-ring of the steroid nucleus. An important class of steroids containing many pharmacologically active compounds are the pregnanes. The corticosteroids, on the D-ring characterised by the 17.beta.hydroxyacetyl and 17.alpha.-hydroxy substituents (which both may be esterified), are particularly important representatives of this class. Many corticosteroids possess on the C16-position also a.alpha.-hydroxyl or a methyl group which is either.alpha.- or.beta.oriented. Multi-step chemical syntheses of pregnanes starting from the readily available above-mentioned 17-oxo steroids are well known in the art as illustrated by J. Org. Chem. 1979, 44, 1582 or by Bull. Chem. Soc. Jpn. 1985, 58, 981 and by its references cited under 3) or Chem. Soc. Rev. 1983, 12, 75 or by U.S. Pat. No. 4,500,461 and by its references cited in its introduction. An important group of syntheses of corticosteroids makes use of steroids with an (optionally substituted) 17-methylene group as starting compounds. These may be prepared from the corresponding 17-oxo steroids by well known methods. In case the starting steroid contains also a 9.alpha.-hydroxyl group, the first step is without exception a dehydration to a 9(11)-dehydro steroid. The reason is that the presence of the tertiary 9.alpha.-hydroxyl function is assumed to cause undesired rearrangements, especially in the steroid A-ring, as reported by C. G. Bergstrom and R. M. Dodson, Chemistry and Industry 1961, 1530 and L. J. Chinn & R. M. Dodson, J. Org. Chem. 1959, 24, 879. Because 9(11)-dehydro steroids are believed up to now to be more stable, the dehydration of 9.alpha.-hydroxy steroids seemed to be an obvious reaction to begin, previous to building a side chain of a corticosteroid. No corticosteroid syntheses are known which take along the 9.alpha.-hydroxyl group. Web site: http://www.delphion.com/details?pn=US05194602__
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9-alpha-hydroxy steroids, process for their preparation, process for the preparation of the corresponding 9(11)-dehydro derivatives and pharmaceutical preparations containing said steroids Inventor(s): Batist; Jacobus N. M. (Kwintsheul, NL), Marx; Arthur F. (Delft, NL), Van Zoest; Willem J. (Schiedam, NL), Kapur; Jagdish C. (Delft, NL) Assignee(s): Roussel UCLAF (Romainville, FR) Patent Number: 5,565,588 Date filed: October 4, 1994 Abstract: New 9-alpha-hydroxy steroids are prepared by the introduction of substituents on the D-ring of 9-alpha-hydroxy-androst-4-ene-3,17-dione.The resulting compounds are useful intermediates in the synthesis of corticosteroids. Excerpt(s): The invention relates to new 9-alpha-hydroxy steroids with a substituted Dring, to their preparation and to the subsequent dehydration to 9,11-dehydro steroids. Nearly all steroids which are currently used as pharmaceuticals originate either directly or indirectly from steroid raw materials found in nature Originally diosgenin constituted the main supply of this raw material. In order to become less dependent of this specific compound one has investigated whether other steroids which are abundantly available, viz. cholesterol, sitosterol, stigmasterol and campesterol could also be used as starting material. Microbiological syntheses were developed to prepare in one step from said materials 17-oxo steroids, especially androst-4-ene-3,17-dione. From the latter compound it was possible obtain 9-alpha-hydroxy-androst-4-ene-3,17dione using a second microbiological step. This compound can be prepared even directly from the above-mentioned sterols, for example by using a specific Mycobacterium fortuitum strain, see British patent GB 1530730. 9-Alphahydroxyandrost-4-ene-3,17-dione is for several syntheses which lead to pharmacologically active steroids a suitable starting compound, because it is apt to functionalisation in the D-ring, as well as in the C-ring of the steroid nucleus. An important class of steroids containing many pharmacologically active compounds are the pregnanes. The corticosteroids, on the D-ring characterized by the (optionally esterified) 17-beta-hydroxyacetyl, 17-alpha-hydroxy substituents are particularly important representatives of this class. Many possess also a methyl or hydroxyl group on C.sup.16. Multi-step chemical syntheses of pregnanes starting from the readily available above-mentioned 17-oxo steroids are well known in the art as illustrated by J. Org. Chem., Vol. 44, no. 9 (1979), 1582-1584 or by Bull. Chem. Soc. Jpn., Vol. 58, 981-986 (1985) and by its references cited under 3) or by U.S. Pat. No. 4,500,461 and by its references cited in its introduction. In case the starting compound is a 9-alpha-hydroxy steroid, the first step is without exception a dehydration to a 9,11-dehydro steroid. The reason probably is that the presence of the tertiary 9-alpha-hydroxyl function is assumed to cause undesired rearrangements, especially in the steroid A-ring. See e.g. C. G. Bergstrom and R. M. Dodson, Chemistry and Industry, 1530 (1961) and L. J. Chinn & R. M. Dodson, J. Org. Chem. 24 (1959), 879. Because 9,11-dehydro steroids are believed to be more stable and a good starting point for the introduction of substituents on C.sup.9 and C.sup.11 the dehydration of 9-alpha-hydroxy steroids seemed to be an obvious reaction to begin every synthesis. Web site: http://www.delphion.com/details?pn=US05565588__
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Anaesthetic steroids of the androstance and pregnane series Inventor(s): Cook; Martin Christopher (Chalfont St. Peter, EN), Lawrence; Robin (London, EN), Phillipps; Gordon Hanley (Wembley, EN), Hunter; Anne Christine (Ruislip, EN), Newall; Christopher Earle (London, EN), Stephenson; Leslie (London, EN), Weir; Niall Galbraith (London, EN) Assignee(s): Glaxo Laboratories Limited (Greenford, EN) Patent Number: 3,953,429 Date filed: February 19, 1974 Abstract: Steroids of the androstane and pregnane series possessing a 2.alpha.-hydrogen or halogen or an alkyl group; a 3.alpha.-hydroxy or acyloxy group, a 3.beta.-hydrogen or alkyl group; an 11.beta.-hydrogen or hydroxy group or an epoxy group linked also to the 9-position; an 11.alpha.-hydrogen or alkyl or allyl group; or an 11-oxo group; a 16 hydrogen or halogen or a methyl or dimethyl group; a 20-oxo or ethylenedioxy group; and a 20-methyl or alkoxy group. The compounds may be unsaturated at the 1(2), 8(9) or 9(11) positions.The compounds possess anaesthetic properties. Excerpt(s): This invention is concerned with improvements in or relating to compounds of the pregnane and androstane series having useful anaesthetic activity. It has long been known that a number of steroids give rise to profound depression of the central nervous system and act pharmacodynamically as anaesthetics or hypnotics. Such compounds have been the subject of considerable study in any attempt to find anaesthetics to replace such substances as thiopentone sodium normally used but well known to be accompanied by some degree of hazard and disadvantage. The literature shows that very many steroid compounds have been studied in this regard. Reviews and discussions of some of the work carried out are to be found, for example, in "Methods in Hormone Research" (Edited by Ralph I. Dorfman, Vol. III Part A, Academic Press, London and New York, 1964, pages 415-475); H. Witzel, Z. Vitamin HormonFermentforsch 1959, 10, 46-74; H. Selye, Endocrinology, 1942, 30, 437-453; S. K. Figdor et al., J. Pharmacol. Exptl. Therap., 1957, 119, 299-309 and Atkinson et al., J. Med. Chem. 1965, 8, 426-432. A thorough review of the literature indicates that anaesthetic steroids generally possess poor activity and/or long induction periods. With such compounds a variety of undesired side effects such as paraesthesia and vein damage have been noted. Steroids possessing anaesthetic activity hitherto described are generally relatively simple pregnane derivatives, often hydroxylated in the 3-position, the general trend having been in the latter case to study 3.beta.-hydroxy compounds rather than 3.alpha.hydroxy compounds. Web site: http://www.delphion.com/details?pn=US03953429__
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Anaesthetic steroids of the androstane series and process for preparing same Inventor(s): Phillipps; Gordon Hanley (Wembley, EN), Marshall; David Robert (Chalfont St. Peter, EN) Assignee(s): Glaxo Laboratories Limited (Greenford, EN) Patent Number: 3,989,686 Date filed: September 13, 1974
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Abstract: Anaesthetic steroids of the androstane and 19-norandrostane series are described, the steroids possessing a 3.alpha.-hydroxy group, a 17.alpha.-hydrogen atom and at the 17.beta.-position a --COSH or esterified --COSH group. Excerpt(s): This invention is concerned with compounds of the and rostane series having anaesthetic activity. It has long been known that a number of steroids give rise to profound depression of the central nervous system and act pharmacodynamically as anaesthetics or hypnotics. Such compounds have been the subject of considerable study in an attempt to find anaesthetics to replace such substances as thiopentone sodium normally used but well known to be accompanied by some degree of hazard or disadvantage. The literature shows that very many steroid compounds have been studied in this regard. Reviews and discussions of some of the work carried out are to be found, for example, in "Methods in Hormone Research" (Edited by Ralph I. Dorfman, Vol. III Part A, Academic Press, London and New York, 1964, pages 415-475); H. Witzel, Z. Vitamin Hormon-Fermentforsch 1959, 10, 46-74; H. Selye, Endocrinology, 1942, 30, 437-453; S.K. Figdor et al., J. Pharmacol. Exptl. Therap., 1957, 119, 299-309 and Atkinson et al., J. Med. Chem. 1965, 8, 426-432. A thorough review of the literature indicates that many anaesthetic steroids possess poor activity and/or long induction periods. A variety of undesired side effects such as paraesthesia and vein damage have also been noted. Web site: http://www.delphion.com/details?pn=US03989686__ •
Androstane steroids as neurochemical initators of change in human hypothalamic compositions and methods Inventor(s): Berliner; David L. (Atherton, CA), Adams; Nathan William (Salt Lake City, UT), Jennings-White; Clive L. (Salt Lake City, UT) Assignee(s): Pherin Pharmaceuticals, Inc. (Menlo Park, CA) Patent Number: 5,965,552 Date filed: December 15, 1998 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human semiochemical, e.g. an Androstane steroid, or a pharmaceutical composition containing a semiochemical, such that the ligand semiochemical binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): The application also relates to another continuation-in-part of U.S. patent application Ser. No. 07/903,604, U.S. patent application Ser. No. 08/077,359, filed Jun. 15, 1993, and to commonly assigned, co-pending U.S. patent application Ser. No. 07/903,525, filed Jun. 24, 1992 (a continuation-in-part of U.S. application Ser. No. 07/707,862, filed May 31, 1991, which in turn is a continuation-in-part of U.S. Application Serial No. 07/638,743, filed Jan. 7, 1991, now abandoned) entitled "Estrene Steroids as Neurochemical Initiators of Change in Human Hypothalamic Function and Related Pharmaceutical Compositions and Methods"; and to the commonly assigned, continuation-in-part of 07/903,525, U.S. patent application Ser. No. 08/077,140. The aforementioned U.S. patent applications are each incorporated herein by reference. Finally, this application may relate to a co-pending U.S. patent application entitled
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"Fragrance Compositions Containing Human Pheromones", filed Mar. 24, 1992, U.S. Ser. No. 07/856,435. This invention relates generally to pharmaceutical compositions and methods for effectuating change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals. More particularly, the invention relates to the use of certain Androstene steroids as neurochemical effectuators of physiology and behavior. Web site: http://www.delphion.com/details?pn=US05965552__ •
Angiostatic steroids Inventor(s): Clark; Abbot F. (Arlington, TX), Conrow; Raymond E. (Fort Worth, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 6,011,023 Date filed: August 27, 1997 Abstract: Methods and compositions for preventing and treating neovascularization with steroids is disclosed. Excerpt(s): This invention relates to angiostatic steroids for controlling ocular hypertension. The compounds are also useful in preventing and treating neovascularization. Specifically, the invention is directed to new angiostatic steroids, pharmaceutical compositions comprising the angiostatic steroids, and methods of treatment which comprise administering these compositions to treat ocular hypertension, including controlling ocular hypertension associated with primary open angle glaucoma, and to treat neovascularization. In addition, the compounds can be used in combination with glucocorticoids to treat ocular inflammation without the significant intraocular pressure rise commonly associated with the use of glucocorticoids. Steroids functioning to inhibit angiogenesis in the presence of heparin or specific heparin fragments are disclosed in Crum, et al., A New Class of Steroids Inhibits Angiogenesis in the Presence of Heparin or a Heparin Fragment, Science, Vol.230, pp.1375-1378 (Dec. 20, 1985). The authors refer to such steroids as "angiostatic" steroids. Included within the new class of steroids found to be angiostatic are the dihydro and tetrahydro metabolites of cortisol and cortexolone. In a follow-up study directed to testing a hypotehsis as to the mechanism by which the steroids inhibit angiogenesis, it was shown that heparin/angiostatic steroid compositions cause dissolution of the basement membrane scaffolding to which anchorage dependent endothelia are attached resulting in capillary involution; see, Ingber, et al., A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids: Induction of Capillary Basement Membrane Dissolution, Endocrinology Vol. 119, pp.1768-1775 1986). A group of tetrahydro steroids useful in inhibiting-angiogenesis is disclosed in International Patent Application No. PCT/US86/02189, Aristoff, et al., (The Upjohn Company). The compounds are disclosed for use in treating head trauma, spinal trauma, septic or traumatic shock, stroke and hemorrhage shock. In addition, the patent application discusses the utility of these compounds in embryo implantations and in the treatment of cancer, arthritis and arteriosclerosis. Some of the steroids disclosed in Aristoff et al. are disclosed in U.S. Pat. No. 4,771,042 in combination with heparin or a heparin fragment for inhibiting angiogenesis in a warm blooded animal. Web site: http://www.delphion.com/details?pn=US06011023__
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Angiostatic steroids and methods and compositions for controlling ocular hypertension Inventor(s): Clark; Abbot F. (Arlington, TX), Conrow; Raymond E. (Fort Worth, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 5,698,545 Date filed: May 6, 1996 Abstract: Angiostatic steroids for use in controlling ocular hypertension are disclosed. Pharmaceutical compositions of the angiostatic steroids and methods for their use in treating ocular hypertension, including controlling the ocular hypertension associated with primary open angle glaucoma, are disclosed. In addition, the combination of the compounds with glucocorticoids for the prevention of elevated IOP during the treatment of inflammation is disclosed. Excerpt(s): This invention relates to angiostatic steroids and their use in methods and compositions for controlling ocular hypertension. Specifically, the invention is directed to new angiostatic steroids, pharmaceutical compositions comprising the angiostatic steroids, and methods of treatment comprising administering these compositions to treat ocular hypertension, including controlling ocular hypertension associated with primary open angle glaucoma. In addition, the compounds can be used in combination with glucocorticoids to control the ocular hypertension very commonly associated with the use of glucocorticoids in the treatment of ocular inflammation. Steroids functioning to inhibit angiogenesis in the presence of heparin or specific heparin fragments are disclosed in Crum, et el., A New Class of Steroids Inhibits Angiogenesis in the Presence of Heparin or a Heparin Fragment, Science, Vol.230, pp.1375-1378 (Dec. 20, 1985). The authors refer to such steroids as "angiostatic" steroids. Included within the new class of steroids found to be angiostatic are the dihydro and tetrahydro metabolites of cortisol and cortexolone. In a follow-up study directed to testing a hypothesis as to the mechanism by which the steroids inhibit angiogenesis, it was shown that heparin/angiostatic steroid compositions cause dissolution of the basement membrane scaffolding to which anchorage dependent endothelia are attached resulting in capillary involution; see, Ingber, et al., A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids: Induction of Capillary Basement Membrane Dissolution, Endocrinology 119, pp.1768-1775 1986). A group of tetrahydro steroids useful in inhibiting angiogenesis is disclosed in International Patent Application No. PCT/U.S. Pat. No. 86/02189, Aristoff, et al., (The Upjohn Company). The compounds are disclosed for use in treating head trauma, spinal trauma, septic or traumatic shock, stroke and hemorrhage shock. In addition, the patent application discusses the utility of these compounds in embryo implantation and in the treatment of cancer, arthritis and arteriosclerosis. The compounds are not disclosed for ophthalmic use. Web site: http://www.delphion.com/details?pn=US05698545__
Patents 341
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Antiandrogenic [3,2-c]pyrazole and [3,2-d]triazole steroids Inventor(s): Hofmeister; Helmut (Berlin, DE), Bittler; Dieter (Berlin, DE), Michna; Horst (Berlin, DE), Habenicht; Ursula (Berlin, DE), Fritzemeier; Karl-Heinrich (Berlin, DE), Nishino; Yukishige (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin and Bergkamen, DE) Patent Number: 5,389,624 Date filed: April 27, 1993 Abstract: [3,2-c]Pyrazole and [3,2-d]triazole steroids are useful anti-androgens. Excerpt(s): as well as to a process for the preparation thereof, to pharmaceutical preparations containing these steroid azoles of general Formula I, as well as to their usage for the production of medicinal agents. 2'-mesyl-17.alpha.-methyl-11-methylene2'H-triazolo[4',5':2,3]androst-4-en- 17.beta.-ol, 11.beta.-fluoro-2'-mesyl-17.alpha.-methyl2'H-triazolo[4',5':2,3]androst-4 -en-17.beta.-ol. Steroido [3,2-c]pyrazoles of the stanozolol type (stanozolol=17.alpha.-methyl-5.alpha.-androstano[3,2-c]pyrazol-17.beta.-ol ) have been disclosed in EP 0 207 375 Al. These compounds are androstanes of the 5.alpha.-H or 4-ene series exhibiting a pyrazole ring condensed to the A ring of the steroid and substituted at the N-1. These compounds have antiandrogenic properties and are peripherally selectively effective. EP 0 207 375 Al indicates 17.alpha.-ethynyl-1'-mesyl1'H-5.alpha.-androstano[3,2-c]pyrazol-17.beta.- ol and 17.alpha.-ethynyl-1'-mesyl-4methyl-1'H-androst-4-eno[3,2-c]pyrazol-17.bet a.-ol as the especially preferred compounds. Web site: http://www.delphion.com/details?pn=US05389624__
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Anti-androgenic steroids Inventor(s): Robinson; Cecil H. (Pylesville, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 4,087,461 Date filed: August 22, 1977 Abstract: 6 (H)-5,10-seco-4,5-dieneketo steroids are disclosed which exhibit antiardrogenic properties. Excerpt(s): The present invention relates to certain new and useful steroids which demonstrate anti-androgenic properties. These steroids are 5,10-secosteroids that have been found to be potent irreversible inhibitors of the enzyme.DELTA.sup.5 -3ketosteroid isomerase which is involved in androgen biosynthesis. In addition, certain of the steroids of the invention compete reversibly with 5-.alpha.-dihydrotestosterone for binding to the prostatic cytoplasmic receptor protein while others inhibit the enzyme prostatic testosterone 5-.alpha.-reductase. The anti-androgenic properties of the present compounds indicate such utility as the control of abnormal growth of the human prostate, e.g. in the therapy of human prostatic cancer. (1) Cf. R. R. Rando, Science, 185, 320 (1974). (2) K. Bloch, Acc. Chem. Res. 2, 193 (1969); K. Endo, G. M. Helmkamp, and K. Bloch, J. Biol. Chem. 245, 4293 (1970); M. Morisaka and K. Bloch, Bioorg. Chem., 1 188 (1971). (3) R. R. Rando, J. Am. Chem. Soc., 95, 4438 (1973); R. R. Rando and J. De Mairena, Biochem. Pharmacol., 23, 463 (1974); R. C. Hevey, J. Babson, A. L. Maycock, and R. H. Abeles, J. Am. Chem. Soc., 95, 6125 (1973). (4) R. H. Abeles and C. T. Walsh, J.
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Am. Chem. Soc. 95, 6124 (1973). (5) P. Talalay and A. M. Benson, Enzymes, 6, 591 (1972). (6) S. K. Malhotra and H. J. Ringold, J. Am. Chem. Soc., 87, 3228 (1965). Web site: http://www.delphion.com/details?pn=US04087461__ •
Antiglucocorticoid steroids for the treatment of anxiety disorders Inventor(s): Peeters; Bernardus Wynand Mathijs Marie (Herpen, NL) Assignee(s): Akzo Nobel N.V. (Arnhem, NL) Patent Number: 5,741,787 Date filed: January 18, 1996 Abstract: The invention relates to the use of antiglucocorticoid steroids for the manufacture of a pharmaceutical composition for the treatment of anxiety disorders. Excerpt(s): The invention relates to the use of antiglucocorticoid steroids for the manufacture of a pharmaceutical composition for the treatment of anxiety disorders. Antiglucocorticoid steroids are a well known group of steroids which exhibits affinity for the glucocorticoid receptor (GR) and reduce completely or to a considerable extent the action of cortisol. For example, 11.beta.-substituted steroids having antiglucocorticoid activity are disclosed in EP-A-190759 and EP-A-57115. Other steroids having antiglucocorticoid activity are 10.beta.-substituted steroids as disclosed in EP-A188396. It has now been found that antiglucocorticoid steroids also exert anxiolytic effects, which make these steroids useful for the treatment of anxiety disorders. Anxiety disorder is a rather broad concept including for instance general anxiety, panic disorder, and various kinds of withdrawal symptoms (see: Diagnostic and Statistical Manual of Mental Disorders, 3 RD ED DSM-III, Washington, American Psychiatric Ass., p. 225-239, 1980). Web site: http://www.delphion.com/details?pn=US05741787__
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A-seco steroids effective at treating ophthalmic pathological neovascularization and controlling intraocular pressure Inventor(s): Conrow; Raymond E. (Crowley, TX), Clark; Abbot F. (Arlington, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 5,929,111 Date filed: December 17, 1997 Abstract: A-seco steroids are disclosed. Methods of use are disclosed for treating ophthalmic pathological neovascularization and controlling intraocular pressure. Excerpt(s): This invention relates to A-seco steroids. The compounds are also useful in preventing and treating neovascularization and may also be used to control ocular hypertension. Specifically, the invention is directed to A-seco steroids, pharmaceutical compositions comprising the A-seco steroids, and methods of treatment which comprise administering these compositions to treat ocular hypertension, including controlling ocular hypertension associated with primary open angle glaucoma, and to treat neovascularization. In addition, the compounds can be used in combination with glucocorticoids to treat ocular inflammation without the significant intraocular pressure rise commonly associated with the use of glucocorticoids. Steroids functioning to inhibit
Patents 343
angiogenesis in the presence of heparin or specific heparin fragments are disclosed in Crum, et al., A New Class of Steroids Inhibits Angiogenesis in the Presence of Heparin or a Heparin Fragment, Science, Vol. 230, pp. 1375-1378 (Dec. 20, 1985). The authors refer to such steroids as "angiostatic" steroids. Included within the new class of steroids found to be angiostatic are the dihydro and tetrahydro metabolites of cortisol and cortexolone. In a follow-up study directed to testing a hypothesis as to the mechanism by which the steroids inhibit angiogenesis, it was shown that heparin/angiostatic steroid compositions cause dissolution of the basement membrane scaffolding to which anchorage dependent endothelia are attached resulting in capillary involution; see, Ingber, et al., A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids: Induction of Capillary Basement Membrane Dissolution, Endocrinology, Vol. 119, pages 1768-1775 (1986). More recently, other theories regarding the mechanism of action of angiostatic steroids have developed. For example, angiostatic steroid induced inhibition of neovascularization may occur due to: inhibition of vascular endothelial cell proliferation, Cariou, et al., Inhibition of Human Endothelial Cell Proliferation by Heparin and Steroids, Cell Biology International Reports, Vol. 12, No. 12, pp. 1037-1047 (December, 1988); or inhibition of vascular endothelial cell plasminogen activator activity, Ashino-Fuse, et al., Medroxyprogesterone Acetate, An Anti-Cancer and AntiAngiogenic Steroid, Inhibits the Plasminogen Activator in Bovine Endothelial Cells, Int. J. Cancer, 44, pp. 859-864 (1989). A group of tetrahydro steroids useful in inhibiting angiogenesis is disclosed in International Patent Application No. PCT/US86/02189, Aristoff, et al., (The Upjohn Company). The compounds are disclosed for use in treating head trauma, spinal trauma, septic or traumatic shock, stroke and hemorrhage shock. In addition, the patent application discusses the utility of these compounds in embryo implantation and in the treatment of cancer, arthritis and arteriosclerosis. Some of the steroids disclosed in Aristoff et al. are disclosed in U.S. Pat. No. 4,771,042 in combination with heparin or a heparin fragment for inhibiting angiogenesis in a warm blooded animal. Web site: http://www.delphion.com/details?pn=US05929111__ •
Biological process for producing steroids hydroxylated at the 25-position Inventor(s): Takeda; Koji (Iwata, JP), Terasawa; Tadashi (Fujisawa, JP), Dobashi; Kazuyuki (Hadano, JP), Yoshioka; Takeo (Ayase, JP) Assignee(s): Mercian Corporation (Tokyo, JP), Chugai Seiyaku Kabushiki Kaisha (Tokyo, JP) Patent Number: 6,043,050 Date filed: December 23, 1998 Abstract: A biological process for producing steroids hydroxylated at the 25-position thereof comprises adding steroids (excluding cholesterol) to the cells or culture liquid of a microorganism of the genus Amycolata or Sphingomonas capable of hydroxylating the steroids at the 25-position thereof to convert a hydrogen atom bonded to a carbon atom at the 25-position of each steroid into hydroxyl group. By this process, steroids(other than cholesterol) can be biologically hydroxylated at the 25-position by using microorganisms other than those of the genus Streptomyces. Excerpt(s): The present invention relates to a process for biologically hydroxylating the 25-position of steroids other than cholesterol. For the biological hydroxylation of steroids at the 25-position, there is already known a process wherein microorganisms of the genus Streptomyces capable of hydroxylating steroids at the 25-position thereof are
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used [Japanese Patent Unexamined Published Application (hereinafter referred to as "J. P. KOKAI") No. Hei 7-123997]. Concretely, Streptomyces sp. HB-103 is mentioned therein as the microorganisms of the genus Streptomyces. With this kind of microorganisms, steroids having complicated structures can be efficiently, easily and directly hydroxylated at the 25-position. The object of the present invention is to provide a biological process for hydroxylating steroids, other than cholesterol, at the 25-position thereof with microorganisms of a genus other than the genus Streptomyces. Web site: http://www.delphion.com/details?pn=US06043050__ •
Corticosteroids from 17-keto steroids via 20-cyano-.DELTA.sup.17 (.sup.20)-pregnanes Inventor(s): Walker; Jerry A. (Oshtemo Township, Kalamazoo County, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,600,538 Date filed: August 2, 1984 Abstract: The process of the present invention transforms 17-keto steroids (I) to the corresponding corticoids (IV) in three steps. Excerpt(s): The transformation of 17-keto steroids to corticoids is well known to those skilled in the art. Numerous routes have been utilized. See, for example, U.S. Pat. Nos. 4,041,055, 4,216,159, 4,342,702 and 4,411,835. The addition of an.alpha.-nitrile anion to ketones has been reported, see Synthesis 92 (1975), including 17-keto steroids, see J. Org. Chem. 43, 4374 (1978). The J. Org. Chem. 43, 4374 (1978) publication discloses the addition of the lithiated mono anion of 3-unsubstituted propionitrile to a 17-keto steroid to give a 17.beta.-hydroxy-17.alpha.-substituted steroid which upon dehydration with thionyl chloride gives a 20-cyano-.DELTA.sup.17 (.sup.20)-steroid, however the oxidation of these 20-cyano-.sup.17 (.sup.20) steroids to 17.alpha.-hydroxy 20-keto steroid does not work well, see J. Org. Chem. 44, 702 (1979). The -OR.sub.21 substituent permits efficient oxidation of the 20-cyano-.DELTA.sup.17 (.sup.20)-steroid (III) to the corticoid (IV). The addition of a.beta.-mettalo-.alpha.-substituted propionitrile to a 17keto steroid has not been reported. It is surprising and unexpected that the.alpha.metallo-.beta.-metalloxypropionitrile dianion (V) adds to the 17-keto steroid (I) without elimination of the -OR.sub.21.alpha. substituent. The oxidation of 21-acetoxy.DELTA.sup.17 (.sup.20)-20-cyanopregnanes to the corresponding 17,21-dihydroxy-20keto steroid derivatives is well known in the steroid literature, see J. Am. Chem. Soc. 76, 5031 (1954); J. Am. Chem. Soc. 70, 1454 (1948); J. Am. Chem. Soc. 71, 2443 (1949); J. Am. Chem. Soc. 77, 196 (1955); Helv. Chim. Acta 34, 359 (1951); and J. Org. Chem. 44, 702 (1979). Web site: http://www.delphion.com/details?pn=US04600538__
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deA-steroids Inventor(s): Furst; Andor (Basel, CH), Keller; Peter (Reinach, CH), Muller; Marcel (Frenkendorf, CH) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,492,797 Date filed: October 4, 1982
Patents 345
Abstract: The present disclosure is directed to 5-oxo- or methylene 17.beta.-hydroxy saturated or unsaturated deA-steroids wherein the 17.alpha.-position contains a propionic acid or propanol substituent and derivatives thereof wherein the hydroxy group at the 17-position forms a lactone ring with the carboxy substituent when the substituent at position 21 is carboxy. The deA-steroids and derivatives of the present disclosure are useful as potassium-sparing diuretics or for flushing oedemas. Excerpt(s): The present invention relates to novel deA-steroids, a process for their manufacture and pharmaceutical preparations thereof. (h) R.sup.1 is absent and R.sup.2 is lower alkyl when a 9(10)-double bond is present, the C and D rings are saturated, n is zero and Z is --COA, and salts thereof where Z is carboxy. As used herein, the term "alkyl" means straight- or branched-chain saturated aliphatic hydrocarbon groups preferably containing 1-8 carbon atoms. Representative of such groups are methyl, ethyl, isopropyl, butyl, pentyl, hexyl and the like. Web site: http://www.delphion.com/details?pn=US04492797__ •
Dehydrogenation agents based on derivatives of selenium and their use in the dehydrogenation in the 1,4 positions of steroids Inventor(s): Barton; Derek H. R. (Gif-sur-Yvette, FR), Motherwell; William B. (Gif-surYvette, FR) Assignee(s): Roussel Uclaf (Paris, FR) Patent Number: 4,434,080 Date filed: May 18, 1982 Abstract: Derivatives of selenium as dehydrogenation agents employed in the presence of an oxidation agent consisting of oxidized derivatives of possibly substiuted iodoaromatic compounds, particularly where the derivatives of selenium are employed in catalytic amounts; as well as a process of dehydrogenation 3-oxygenated steroids into the corresponding 3-oxygenated.DELTA.sup.1,4 steroids. Excerpt(s): The present invention concerns new dehydrogenation agents based on derivatives of selenium and their use in the dehydrogenation in the 1,4 positions of steroids. (b) This is a method which gives rise to secondary reactions due to the formation of selenic acid or other derivatives occurring from the reduction of the benzene-seleninic anhydride. These two inconveniences make the method difficult to utilize on an industrial scale. While the authors disclose one example to a catalytic dehydrogenation of Lanostan-3-one using t.-butylhydroperoxide and diphenyl diselenide, the yield of the desired lanost-1-en-3-one was relatively low and the product obtained had a low melting point range, indicating contamination. Web site: http://www.delphion.com/details?pn=US04434080__
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Determination of steroids by competitive immunoassay Inventor(s): Williams; Gregg T. (Villa Park, IL), Groskopf; William R. (Libertyville, IL), Baker; Harold N. (Libertyville, IL), Agdeppa; Dalmacio A. (Morton Grove, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,932,431 Date filed: April 16, 1997
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Abstract: A method and kit for measurement of a steroid by means of a competitive immunoassay, preferably a competitive enzyme immunoassay. The method and kit involve the use of a steroid analogue conjugated to a label. The steroids that are amenable to detection by the method and kit of the present invention include estradiol and progesterone. The method comprises the steps of:a. incubating a mixture of a test sample suspected of containing a given steroid, a solid phase coupled to an antibody specific for that steroid, and a conjugate of an analogue of that steroid to form steroid/antibody complexes and conjugate/antibody complexes on said solid phase;b. separating said solid phase from said mixture;c. measuring the amount of label present in said mixture or in said solid phase; andd. determining the amount of steroid in said sample from the amount of label. The kit comprises a solid phase coupled to an antibody specific for a steroid and a conjugate of an analogue of that steroid. Excerpt(s): This invention relates to detection and measurement of steroids in biological fluids, and, more particularly, detection and measurement of steroids by means of competitive immunoassay. Detection and measurement of steroids in biological fluids is important for a variety of reasons. For example, the amount of a particular steroid in a biological fluid can be used to assist in diagnosing the occurrence of an endocrinological disorder, to monitor the amount of hormone required in hormonal replacement therapy, or to assess fertility. Determination of the presence and amount of steroids in a biological fluid can be determined by competitive diagnostic assay. Small molecule, competitive diagnostic assays require a labeled component that can compete with the analyte for available antibody sites. Examples of the labeled component include radioactive tracers, fluorophore/hapten conjugates, and enzyme/hapten conjugates. Typically, the labeled component consists of the analyte or an analogue of the analyte coupled to a label. The labeled component is typically referred to as a conjugate. Estradiol (1,3,5(10)-estratrien-3,17.alpha.-diol) is an analyte, the detection and measurement of which is of great importance in the area of fertility testing. Estradiol is secreted by the ovary and placenta. It is synthesized by the aromatization of androgens in the thecal and granulosa cells of the ovary and placenta. The aromatization is stimulated by follitropin (FSH). Estradiol synthesis in turn stimulates production of lutropin (LH) receptors necessary for the synthesis of androgen precursors. Web site: http://www.delphion.com/details?pn=US05932431__ •
D-Homo-pregnene steroids Inventor(s): Alig; Leo (76 Heidenlochstrasse, Liestal, CH), Furst; Andor (14 Magnolienpark, Basel, CH), Muller; Marcel (10 Quellenweg, Frenkendorf, CH), Kerb; Ulrich (8 Waitzstrasse, Berlin, DT), Wiechert; Rudolf (5 Petzowerstrasse, Berlin, DT) Assignee(s): none reported Patent Number: 4,026,922 Date filed: October 2, 1975 Abstract: The present disclosure relates to novel D-homo-pregnene steroids useful as progestational agents. Excerpt(s): An acyloxy group can be derived from a saturated or unsaturated aliphatic caboxylic acid, a cycloaliphatic carboxylic acid, an araliphatic carboxylic acid or an aromatic carboxylic acid, said acids preferably containing up to 15 carbon atoms. Examples of such acids are formic acid, acetic acid, pivalic acid, propionic acid, butyric acid, caproic acid, oenanthic acid, undecylenic acid, oleic acid, cyclopentylpropionic
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acid, cyclohexylpropionic acid, phenylacetic acid and benzoic acid. Alkanoyloxy groups containing from 1 to 7 carbon atoms are especially preferred. Alkoxy groups can be straight-chain or branched-chain groups and preferably contain up to 15 carbon atoms. Lower alkoxy groups are especially preferred, particularly the methoxy and ethoxy groups. Lower alkyl groups preferably contain from 1 to 4 carbon atoms, especially the methyl and ethyl groups. In 6,7-saturated D-homosteroids of formula I, a substituent in the 6-position can have.alpha. - or.beta. -configuration, the.alpha. -isomers being preferred. with the formation of a.DELTA.sup.4 -3-ketone. Web site: http://www.delphion.com/details?pn=US04026922__ •
Drugs for topical application of sex steroids in the treatment of dry eye syndrome, and methods of preparation and application Inventor(s): Lubkin; Virginia (One Blackstone Pl., New York, NY 10471) Assignee(s): none reported Patent Number: 5,041,434 Date filed: May 7, 1990 Abstract: A topical drug application for the alleviation of keratoconjunctivitis sicca (dry eye syndrome) is comprised of a solution of sex steroids or their derivatives suspended or dissolved in a vehicle, and the method of preparation and application of the same. In the preferred embodiments, the sex steroid consists essentially of conjugated estrogen in a lipid vehicle or a derivative of estrogen known as 17 beta-Estradiol 3-phosphate disodium dissolved in an aqueous vehicle having a pH of between 6 and 8. Excerpt(s): This invention relates to drugs for the topical application of sex steroids in the treatment of human dry eye syndrome (keratoconjunctivitis sicca) and, more specifically, to the preparation and application of estrogen and its derivatives in lipid or aqueous vehicles for the topical treatment of the ocular surface tissues. In the specification and claims hereinafter the term `sex steroids` is defined to include estrogen, progesterone, testosterone, dehydroepiandrosterone and chemical variants and derivatives of the same. The high incidence of keratoconjunctivitis sicca in the population of postmenopausal women is attended by symptoms ranging from mild foreign body sensation to frank pain and visual loss due to ocular surface abnormalities. Web site: http://www.delphion.com/details?pn=US05041434__
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Electrochemical reduction of.alpha.,.beta.-unsaturated keto steroids Inventor(s): Junghans; Klaus (Berlin, DT) Assignee(s): Schering Aktiengesellschaft (Berlin & Bergkamen, DT) Patent Number: 3,990,956 Date filed: January 14, 1975 Abstract: A process for the preparation of keto steroids by electrochemical reduction, comprising electrolyzing a.alpha.,.beta.-unsaturated keto steroid in a nonaqueous nitrogen-containing solvent containing an electrolyte which is at least one of:A. a quaternary ammonium salt of the general formula NR.sub.1 R.sub.2 R.sub.3 R.sub.4 X, wherein R.sub.1.sub.+4 represent an alkyl, aryl, or aralkyl residue, orB. an alkali or alkaline earth salt of X, wherein X is sufficient anion for charge equalization and
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represents halogen, tetrafluoborate, sulfate, perchlorate, alcoholate, arylsulfonate or alkylsulfonate. Excerpt(s): This invention relates to the preparation of keto steroids from.alpha.,.beta.unsaturated keto steroids.alpha.,.beta.-Unsaturated keto steroids within the scope of this invention are understood to mean those steroids having at least one double bond in conjugation to a keto group, such as, for example,.DELTA.sup.4 -3-keto,.DELTA.sup.1 3-keto,.DELTA.sup.1,4 -3-keto,.DELTA.sup.8 -11-keto, steroids. The term "steroid" is to be used in its broadest sense, e.g. derivatives based on the cyclic ring system known as perhydro-1,2-cyclopentanophenanthrene. It includes, for example, those steroids mentioned in "Steroids", Fieser and Fieser, Reinhold, New York, 1959. In view of the continuing research in this area, it would not be possible nor would it be necessary for the purposes of this invention, to catalog all the different types of steroids that are known. Web site: http://www.delphion.com/details?pn=US03990956__ •
Electrolytic reduction of aromatic steroids Inventor(s): Junghans; Klaus (Berlin, DT) Assignee(s): Schering Aktiengesellschaft (Berlin & Bergkamen, DT) Patent Number: 4,050,998 Date filed: June 8, 1976 Abstract: .DELTA.sup.1,3,5(10) steroids are electrochemically reduced to.delta.sup.2,5(10) steroids in an improved manner by conducting the reduction in liquid ammonia in the presence of an electrolytic salt consisting of an alkali metal salt of a strong acid, when the electrolysis is conducted in a divided cell, and consisting of an alkali metal salt of a weak acid or a mixture of an alkali metal salt of a weak acid and of a strong acid, when the electrolysis is conducted in an undivided cell. Excerpt(s): This invention relates to a process for the production of.DELTA.sup.2,5(10) steroids from.DELTA.sup.1,3,5(10) steroids by electrochemical reduction. In U.S. Pat. 3,720,694 and Fed. Rep. of Germany Pat. No. P 20 63 101.0, Horst Ropke and I disclose a process for the electrolytic reduction in liquid ammonia of 19-nor-.DELTA.sup.1,3,5(10) steroids containing a further reducible double bond. The electrolysis is conducted in an undivided (one-piece) cell employing an alkali metal salt or an alkaline earth salt of a strong acid or an onium complex salt. This results in the reduction of nonaromatic unsaturated groups but the aromatic A-ring is not affected. The electrochemical reduction of simple aromatics in liquid ammonia has been described previously. See, for example, U.S. Pat. Nos. 3,493,477 and 3,488,266. The electrochemical reduction of.DELTA.sup.1,3,5(10) aromatic steroids to the corresponding.DELTA.sup.2,5(10) steroids in methylamine or in other alkyl amine as the solvent is known. See German Patent No. 1,266,300. However, this process has the disadvantage that the amines utilized as the solvent must be separated from the final product after the electrolysis by distillation under reduced pressure or by precipitation with other liquids. Also, due to the low conductivity of the reaction mixture, the current consumption is very high, and a correspondingly strong evolution of heat occurs. This heat must be removed in order to conduct the process on a technical scale. Web site: http://www.delphion.com/details?pn=US04050998__
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Enhanced production of 4,5-unsaturated steroids utilizing methanol solvation Inventor(s): Gelotte; Karl O. (Watchung, NJ), Opalka, Jr. Chester J. (Schodack, NY) Assignee(s): Sterling Drug Inc. (New York, NY) Patent Number: 4,755,595 Date filed: November 1, 1985 Abstract: An improvement in the epoxidation of certain 4,5-unsaturated steroids with peracetic acid, which comprises carrying out the reaction in methanol solution. Excerpt(s): This invention relates to an improvement in the process for the epoxidation of certain 4,5-unsaturated steroids. Clinton and Manson U.S. Pat. No. 3,296,255, issued Jan. 3, 1967, discloses the epoxidation of 17.beta.-acetoxy-4-androsteno[2,3-d]isoxazole with maleic anhydride and hydrogen peroxide in methylene dichloride solution (Example 16). Sterling Drug Inc. British Pat. No. 1,123,770, published Aug. 14, 1968, describes the epoxidation of 17.beta.-hydroxy-4-androsteno[2,3-d]isoxazole with peracetic acid in benzene solution in the presence of sodium acetate and acetic acid to give 17.beta.-hydroxy-4.alpha.,5.alpha.-epoxyandrostano[2,3-d]isoxazole (Example 1a). Web site: http://www.delphion.com/details?pn=US04755595__
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Estrene steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions Inventor(s): Berliner; David L. (Atherton, CA), Adams; Nathan William (Salt Lake City, UT), Jennings-White; Clive L. (Salt Lake City, UT) Assignee(s): Pherin Corporation (Menlo Park, CA) Patent Number: 6,140,316 Date filed: July 21, 1998 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human semiochemical, e.g. an Estrene steroid, or a pharmaceutical composition containing an Estrene steroid, such that the ligand semiochemical binds to a specific neuroepithelial receptor. The steroid is preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): This invention relates generally to pharmaceutical compositions and methods for effectuating change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals. More particularly, the invention relates to the use of certain Estrene steroids as neurochemical effectuators of physiology and behavior. The present invention relates to certain compounds, namely Estrene steroids and related compounds as will be described herein, and methods of using these compounds as human semiochemicals in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g. the reduction of anxiety. Estrene steroids are typified by 17.beta.Estradiol (1,3,5(10)-Estratriene-3,17.beta.-diol), and are characterized by a phenolic 1,3,5(10) A-ring and a hydroxy or hydroxy derivative, such as an ether or ester, at the 3position. The pheromone properties of some Estrene steroids for some mammalian species has been described. Michael, R. P. et al., Nature (1968) 218:746 refers to Estrogens (particularly Estradiol) as a pheromonal attractant of male rhesus monkeys. Parrot, R. F.,
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Hormones and Behavior (1976) 7:207-215, reports Estradiol benzoate injection induces mating behavior in ovariectomized rats; and the role of the blood level of Estradiol in make sexual response (Phoenix, C. H., Physiol. and Behavior (1976) 16:305-310) and female sexual response (Phoenix, C. H., Hormones and Behavior (1977) 8:356-362) in Rhesus monkeys has been described. On the other hand, there is little agreement in the literature as to whether or not pheromones as such play any role in the reproductive behavior and interpersonal communication of mammals (Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", In: Mammalian Olfaction, Reproductive Processes, and Behavior, Doty, R. L., Ed., Academic Press, 1976). An embodiment of the subject invention concerns the nonsystemic, nasal administration of certain Estrene steroids to affect a specific behavioral or physiological response in human subjects, e.g. a reduction of negative affect, mood, and character traits. In particular, nasal administration provides for contacting neuroreceptors of a heretofore poorly understood neuroendocrine structure, commonly known as the vomeronasal organ ("VNO"; also known as "Jacobson's organ"), with one or more steroid(s) or with compositions containing the steroid(s). This organ is accessed through the nostrils of most higher animals--from snakes to humans, and has been associated, inter alia, with pheromone reception in certain species (see generally MullerSchwarze & Silverstein, Chemical Signals, Plenum Press, New York (1980)). The axons of the neuroepithelia of the vomeronasal organ, located supra palatial, form the vomeronasal nerve and have direct synaptic connection to the accessory olfactory bulb and indirect input from there to the cortico-medial amygdaloid forebrain and hypothalamic nuclei of the brain. The distal axons of the terminal is nerve neurons may also serve as neurochemical receptors in the VNO. Stensaas, L. J., et al., J. Steroid Biochem. and Molec. Biol. (1991) 39:553. This nerve has direct synaptic connection with the hypothalamus. Web site: http://www.delphion.com/details?pn=US06140316__ •
Ethynylation of 16-methyl-17-keto steroids Inventor(s): Timko; Joseph M. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,618,456 Date filed: April 26, 1984 Abstract: The process of the present invention transforms 16.alpha.- or 16.beta.-methyl17-keto steroids (I) to the corresponding 17.alpha.-ethynyl-17.beta.-hydroxy-16.alpha.or 16.beta.-methyl steroids (II) without epimerization and loss of stereochemistry of the 16.alpha.- or 16.beta.-methyl group. Excerpt(s): Ethynylation of 17-keto steroids to produce commercially important 17.alpha.-ethynyl-17.beta.-hydroxy steroids is well known to those skilled in the art. See, for example, U.S. Pat. Nos. 2,272,131, 2,843,609, 2,723,280, 2,877,240, 3,470,217, 4,041,055, Steroids by Fieser and Fieser, Reinhold Publishing Co., New York, 1959, pp. 557-591, and J. Am. Chem. Soc. 78, 2477 (1956). The general method of ethynylation is to react the 17-keto steroid with dipotassium acetylide. The advantage of the dipotassium acetylide process is that it can be used with.DELTA.sup.4 -3-keto steroids without having to protect the 3-keto group. However, that procedure cannot be used with 16.alpha.methyl-17-keto, 16.beta.-methyl-17-keto or 16-methylene-17-keto steroids for well known reasons. Commercially the ethynylation of 16.alpha.- or 16.beta.-methyl- as well as 16-methylene-17-keto steroids is important because the 17.alpha.-ethynyl-17.beta.-
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hydroxy-16.alpha.-methyl, 17.alpha.-ethynyl-17.beta.-hydroxy-16.beta.-methyl and 17.alpha.-ethynyl-17.beta.-hydroxy-16-methylene steroids can be transformed to dexamethasone, betamethasone and melengestrol acetate. Metallo-acetylides other than dipotassium acetylide are known. Monosodium acetylide is known, see U.S. Pat. No. 3,470,217 and R. J. Tedeschi, et al., J. Org. Chem. 34, 435 (1969). Mono- and bismagnesium acetylides are known, see L. Skattebol, et al., J. Chem. Soc. 4765 (1956). Although the use of magnesio-acetylides has been reported for 17.alpha.-ethynyl introduction, substantial dimer formation results with both mono- and bismagnesioacetylides, see U.S. Pat. No. 3,704,253. Web site: http://www.delphion.com/details?pn=US04618456__ •
Ethynylation of 16-methylene-17-keto steroids Inventor(s): VanRheenen; Verlan H. (Portage, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,614,621 Date filed: April 20, 1984 Abstract: The process of the present invention transforms 16-methylene-17-keto steroids (I) to the corresponding 17.alpha.-ethynyl-17.beta.-hydroxy-16-methylene steroids (II). Excerpt(s): Ethynylation of 17-keto steroids to produce commercially important 17.alpha.-ethynyl-17.beta.-hydroxy steroids is well known to those skilled in the art. See, for example, U.S. Pat. Nos. 2,272,131, 2,843,609, 2,723,280, 3,275,666, 2,877,240, 3,470,217, 4,041,055, Steroids by Fieser and Fieser, Reinhold Publishing Co., New York, 1959, 557591, and J. Am. Chem. Soc. 78, 2477 (1956). The general method of ethynylation is to react the 17-keto steroid with dipotassium acetylide. The advantage of the dipotassium acetylide process is that it can be used with.DELTA.sup.4 -3-keto steroids without having to protect the 3-keto group. However, that procedure cannot be used with 16.alpha.-methyl-17-keto-, 16.beta.-methyl-17-keto- or 16-methylene-17-keto-steroids for well known reasons. Commercially the ethynylation of 16.alpha.- or 16.beta.-methyl- as well as 16-methylene-17-keto steroids is important because the 17.alpha.-ethynyl17.beta.-hydroxy-16.alpha.-methyl-, 17.alpha.-ethynyl-17.beta.-hydroxy-16.beta.-methyland 17.alpha.-ethynyl-17.beta.-hydroxy-16-methylene-steroids can be transformed to dexamethasone, betamethasone and melengestrol acetate. Metallo-acetylides other than dipotassium acetylide are known. Monosodium acetylide is known, see U.S. Pat. No. 3,470,217 and R. J. Tedeschi, et al., J. Org. Chem. 34, 435 (1969). Mono- and bismagnesium acetylides are known, see L. Skattebol, et al., J. Chem. Soc. 4765 (1956). Although the use of magnesio-acetylides has been reported for 17.alpha.-ethynyl introduction, substantial dimer formation results with both mono- and bismagnesioacetylides, see U.S. Pat. No. 3,704,253. Web site: http://www.delphion.com/details?pn=US04614621__
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Highly concentrated pharmaceutical formulations of steroids and processes for their preparation Inventor(s): Cornelius; Lammert (Boxmeer, NL) Assignee(s): Akzo N.V. (Arnhem, NL) Patent Number: 4,212,863 Date filed: October 23, 1978 Abstract: The invention relates to highly concentrated liquid pharmaceutical formulations of steroids of the oestrane, androstane and (19-nor-)pregnane series comprising tocol or a derivative thereof that is fluid at normal temperature, or mixtures thereof, in an amount of at least 10% by weight of the formulation, and optionally one or more of the usual fluid carriers, such as vegetable oil, benzyl benzoate and/or benzyl alcohol. Excerpt(s): The invention relates to highly concentrated pharmaceutical formulations of steroids of the oestrane, androstane and (19-nor-)pregnane series, the said formulations being fluid at normal temperature, and to processes for their preparation. Injection preparations of steroids are known. Such preparations usually consist of solutions of the steroids in oily carriers, such as arachis oil, sesame oil, olive oil and similar carriers, to which yet other excipients may, if desired, be added, such as benzyl alcohol and benzyl benzoate. Such fluid preparations may be injected almost without damage to tissues, and absorption of the active substance by the organism takes place from the subcutaneous or intramuscular depot thus obtained. The extent and the duration of the absorption depends on various factors including the dosage and concentration of the steroid and the physical properties of the steroid, such as lipophilicity. The upper limit of the concentration is naturally governed by the solubility of the steroid in the carrier. If this solubility is not very great, achievement of the desired effect will necessitate repeating injections at shorter intervals or injecting larger volumes, and there are of course objections to both of these procedures. It is known that the solubility of steroids in vegetable or animal oils can be increased by the addition of excipients such as benzyl alcohol and benzyl benzoate. An objection to the use of such excipients, and specifically benzyl alcohol in somewhat higher concentration, is that these agents may irritate the tissues. Web site: http://www.delphion.com/details?pn=US04212863__
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Imidazolylpiperazinyl steroids Inventor(s): McCall; John M. (Kalamazoo, MI), Ayer; Donald E. (Kalamazoo, MI), Jacobsen; E. Jon (Plainwell, MI), VanDoornik; Frederick J. (Hamilton, MI), Palmer; John R. (Kalamazoo, MI), Karnes; Harold A. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 5,506,354 Date filed: December 1, 1992 Abstract: Disclosed are amino substituted steroids (XI) which contain an imidazolylpiperazinyl group attached to the terminal carbon atom of the C.sub.17 -side chain which are useful as pharmaceutical agents for treating a number of conditions. Excerpt(s): The present invention relates to amino substituted steroids which are useful as pharmaceutical agents. Various amino (substituted) steroids are known with the
Patents 353
amine substitution on either the steroidal ring system or on the side chain of the D-ring at C.sub.17. U.S. Pat. No. 4,456,602 discloses steroidal 21-esters in which there is an amino function in the non-steroidal portion of the ester. Web site: http://www.delphion.com/details?pn=US05506354__ •
Isolation of steroids containing a 5,7-diene functionality from a sterol mixture Inventor(s): Tanabe; Masato (Palo Alto, CA), Johansson; John G. (Menlo Park, CA), Yasuda; Dennis (Campbell, CA) Assignee(s): SRI International (Menlo Park, CA) Patent Number: 5,391,777 Date filed: November 12, 1993 Abstract: A method is provided for isolating 5,7-diene-containing steroids, particularly 3.beta.-ols and esters of 3.beta.-ols, from a sterol mixture. The method involves (1) treating the mixture with a dienophile or with an oxidizable dienophile precursor in combination with an oxidizing agent so as to provide a Diels-Alder adduct of the 5,7diene to be isolated, followed by (2) removal of the adduct from the mixture and (3) regeneration of the 5,7-diene with a suitable reducing agent. The invention also encompasses subsequent purification steps and intermediate modification of the DielsAlder intermediate, e.g., wherein chemical conversion of the Diels-Alder adduct is effected prior to regeneration of the 5,7-diene. Novel compounds which are Diels-Alder adducts of 5,7-diene-containing steroids are provided as well. Excerpt(s): This invention relates generally to synthetic methods involving steroids, and more particularly relates to a novel method for isolating steroids containing a 5,7-diene functionality from a mixture of sterols. The method is especially useful for isolating 5,7diene-containing sterols from a mixture containing yeast sterol metabolites. S.C. Eyley et al., J. C. S. Perkins Trans. I, pp. 731-735 (1976), describe a method for synthesizing 25hydroxyprovitamin D.sub.3 and 25.xi.,26-dihydroxyprovitamin D.sub.3. The method involves initial reaction of the C-22 aldehyde derived by degradation of ergosterol with a Grignard reagent derived from 4-chloro-2-methylbut-1-ene, followed by reductive elimination of the mesylate of the resulting C-22 alcohol. J. P. Moreau et al., J. Org. Chem. 39(14):2018-2023 (1974), is a background reference which describes the synthesis of 5.alpha.-cholesta-7,24-dien-3.beta.-ol and cholesta-5,7,24-trien-3.beta.-ol. Web site: http://www.delphion.com/details?pn=US05391777__
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Male contraceptive steroids and methods of use Inventor(s): Babcock; John C. (Kalamazoo, MI), Campbell; J. Allan (Kalamazoo, MI), Lobl; Thomas J. (Portage, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,297,350 Date filed: October 10, 1978 Abstract: The steroids of the present invention have been found to be useful as male contraceptives when administered orally. Upon cessation of administration of the male contraceptive steroids of the present invention the male promptly regains normal fertility.
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Excerpt(s): Most forms of reversible contraception are practiced by the female member of an animal pair, whether the animal be human or not. With humans, physical (diaphragm and IUD) and chemicl ("the Pill", vaginal creams, foams, ointments, etc.) methods are available. At present there are only two acceptable methods for the human male. These are the condom and bilateral vasectomy. With the condom the failure rate is high, resulting in unwanted pregnancies. Vasectomies for practical purposes must be considered irreversible. Therefore, a method of male human contraception which is both reversible and reliable is highly desirable. With regards to the non-human mammals a male contraceptive is also highly desirable. For non-domestic commercial animals such as horses, cattle, sheep, etc., the present situation is to separate male and female animals so the female may be selectively, artificially inseminated. It would, of course, be simpler to permit the animals to cohabitate under circumstances where the female cannot become pregnant. Domestic animals normally cohabitate because it is virtually impossible to separate male and female cats and dogs in a household. Many times it would be desirable to be able to prevent unwanted pregnancies of domestic animals under cohabitation circumstances. Additionally, with undesirable rodents a male contraceptive would be helpful to decrease fertility and thereby decrease or eliminate the number of undesirable rodents. H. J. Ringold et al. in J. Am. Chem. Soc. 81, 427 (1959) disclose 17.beta.-hydroxy-2.alpha.-methyl-5.alpha.-androstances in general and in particular 17.beta.-hydroxy-2.alpha.-methyl-5.alpha.-androstan-3-one and 17.beta.hydroxy-2.alpha.,17.alpha.-dimethyl-5.alpha.-androstan-3-one. U.S. Pat. No. 2,852,537 discloses 2.alpha.-alkyl-17.beta.-hydroxy-17.alpha.-vinyl and -17.alpha.-ethinylandrost4-ene-3-one type compounds and their anti-androgenic properties. R. Youssefyeh in Tetrahedron Letters 2161 (1964) discloses some 2.alpha.-methyl and ethyl-17.beta.hydroxy-5.alpha.-androstan-3-ones. U.S. Pat. No. 3,846,456 discloses 17.beta.-hydroxy2.alpha.,7.alpha.-dimethylandrost-4-en-3-one and its use as an anti-fertility agent but without stating anti-fertility in the male or female. Web site: http://www.delphion.com/details?pn=US04297350__ •
Method for determining steroids in human body liquids Inventor(s): Pang; Songja (New York, NY), New; Maria (New York, NY) Assignee(s): Cornell Research Foundation, Inc. (Ithaca, NY) Patent Number: 4,431,743 Date filed: October 28, 1980 Abstract: A method for determination of a steroid such as dehydroepiandrosterone sulfate (DS) in a sample of a human body liquid wherein the liquid sample is transferred to a sheet of microfilter paper and dried before being treated with an aqueous solvent to obtain a mixture wherein the dried body liquid is substantially redissolved in the aqueous solution. The mixture is contacted with an aqueous solution of an agent capable of selectively binding the steroid in the presence of a radioisotopically labeled form of steriod whereby part of the labeled steroid and part of the unlabeled steroid present in the sample are bound by forming a complex with the binding agent. Bound steroids are separated from unbound steroids in the aqueous solution and the radioactivity of at least the separated binding agent-steroids-complex or the unbound steroids is performed to determine the concentration of the hormone as a function of measured radioactivity. Additionally, a means for performing the method is disclosed. Excerpt(s): The present invention relates to a micro-method and means for the determination of steroids, in particular of dehydroepiandrosterone sulfate (DS), in
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human body liquids and to a new method and means for detection of abnormal adrenal androgen secretion in the differential diagnosis of excess or deficient androgen producing conditions (e.g., virilism, hirsutism, male precocious puberty or delayed puberty). Recently radioimmunoassay for the measurement of dehydroepiandrosterone sulfate has become available. The usefulness of this assay for the diagnosis of abnormal puberty has been established, (See, e.g., Korth-Schutz S, Levine LS, and New MI: Dehydroepiandrosterone sulfate (DS) levels, a rapid test for abnormal adrenal secretion. J. Clin. Endocrinol Metab 42: 1005,1976.). However, the prior art method for the determination of steroids involves the analysis of blood plasma and requires relatively large amounts of blood for the separation of the blood cell mass from the plasma. Further, sample collection by veno puncture is inconvenient in small infants. In the recently developed radioimmunoassays (RIA), radiological means are employed to detect and/or measure the presence of a steroid in the patient's blood (or urine). In these radioimmunoassay tests, a solution of an antibody of the steroid is placed in contact with a mixture of the steroid, which has been extracted from a sample of the patient's body fluid to be tested and a known amount of the same steroid tagged with a radioactive isotope. The steroid in the test sample and the labeled steroid compete for interaction with the steroid antibody. The resulting steroids-antibody-complex is then separated from the fluid and either fraction may be analyzed radiologically in order to determine the respective proportions of the labeled and unlabeled steroid which became bound to the antibody. The concentration of steroid in the sample can be calculated from this information, since the proportion of labeled and unlabeled steroid will be in the same proportion in both fractions. The radioimmunoassay techniques exhibit a high degree of accuracy and specificity. Until recently the radioimmunoassay techniques required relatively large amounts of blood for the preliminary separation of blood plasma from the hematocrit, and also have the usual disadvantage that samples can be stored only at low temperature, since the liquid samples are easily infected and spoiled by growth of bacteria. A new method developed and applied to the determination of 17.alpha.-hydroxy-progesterone for screening patients with congenital adrenal hyperplasia utilizes eluates of whole blood collected on filter paper. (Pang S., Hotchkiss J., Drash A. L., Levine L. S. and New. M.I.: Microfilter Paper Method for 17.alpha.Hydroxyprogesterone Radioimmunoassay: Its Application for Rapid Screening for Congenital Adrenal Hyperplasia, J. Clin. Endocrinol. Metab. 45, 1003, 1977.). This method has the specificity, accuracy and precision of RIA in whole plasma. Further, it has been shown that concentrations of 17.alpha.-hydroxy-progesterone remain unchanged in dried filter paper blood samples when stored at room temperature for 21 days and, therefore, the filter paper with dried blood may be sent for steroid assay by mail. Although this approach overcomes many of the deficiencies of the prior art, the method includes an extraction step requiring the use of a volatile organic solvent necessary to isolate the steroid of interest. Additionally, a subsequent step requires separation of the residue from the organic solvent. These extra steps take time, can reduce yield and expose lab technicians to the hazards arising from the use of a volatile organic solvent. Web site: http://www.delphion.com/details?pn=US04431743__
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Method for isolation of 3-hydroxy steroids and 3-keto steroids Inventor(s): Weber; Alfred (Berlin, DT), Muller; Rudolf (Berlin, DT), Kurzidim; Johannes (Berlin, DT) Assignee(s): Schering Aktiengesellschaft (Berlin and Bergkamen, DT) Patent Number: 4,057,541 Date filed: June 25, 1976 Abstract: An improved process for isolating 3-hydroxy steroids and 3-keto steroids from mixtures thereof with lipids by dissolving the mixtures in an organic solvent, mixing the dissolved mixture with a metal salt to form insoluble adducts of the steroids, separating the insoluble adducts and splitting the adducts to regenerate the free steroids, which comprises using methyl isobutyl ketone and/or methyl n-amyl ketone as the solvent and calcium bromide as the metal salt. Excerpt(s): This invention relates to a method for isolating 3-hydroxy steroids and 3-keto steroids from mixtures thereof with lipids. Various methods for isolating steroids from such mixtures are known. For example, in German Pat. No. 827,199, a method for isolation of sterols from mixtures is described wherein the mixture is dissolved, preferably in a hydrocarbon solvent, and is heated with a four- to sixteen-fold excess of anhydrous zinc chloride. After cooling of the solution, the precipitated ZnCl-sterol adduct can be separated out and split into the individual components. British Pat. No. 1,164,769 describes a method for the isolation of sterols from mixtures wherein the mixture is dissolved, preferably in a hydrocarbon solvent, the solution is mixed with an aqueous solution of a metal salt which is suitable for complex formation, the water is progressively removed by azetropic distillation, and the precipitated adduct is isolated and split in a conventional manner after cooling of the mixture. Such known methods have the disadvantage that they are technically very costly on account of the high reaction temperature (customarily over 100.degree. C.) and that in the isolation of many 3-hydroxy steroids and 3-oxo steroids considerable loss of product is experienced, since these steroids are destroyed under these conditions. In addition, these known methods often have the disadvantage that the recovery of the metal salt used for formation of the adduct, which is necessary in a method carried out on large scale simply with regard to environmental considerations, is often very costly. The technical scale use of hydrocarbon solvents is also not without its drawbacks, since these are rapidly electrostatically discharged, often have a low ignition point and are often very toxic. Web site: http://www.delphion.com/details?pn=US04057541__
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Method for the microbiological conversion of steroids Inventor(s): Zaffaroni; Pasquale (Mentana, IT), Vitobello; Vincenza (Rome, IT), Gamalerio; Anna M. (Rome, IT) Assignee(s): Snamprogetti S.p.A. (Milan, IT) Patent Number: 4,273,872 Date filed: November 13, 1979 Abstract: A method is disclosed for the microbiological transformation of steroids, especially cholesterol, by employing culture media which contain hydrocarbons rather than carbohydrates. Paraffinic hydrocarbons, particularly normal paraffins from 15 to 20 carbon atoms, are used as the only carbon and energy sources. SP2T (NRRL B-11, 112),
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SP3T bis (NRRL B-11, 113), SP5T (NRRL B-11, 114), SP7T/1 (NRRL B-11, 115), SP742XXA (NRRL B-11, 116), SP731RD (NRRL B-11, 117), and SP734D (NRRL B-11, 118) are bacterial strains which can be used to this purpose. Excerpt(s): This invention relates to a novel method for the microbiological modification of steroids, which is based on their co-oxidation with hydrocarbons. The microbiological conversions of steroids are exploited long since for the production of derivatives having particular pharmacological activities or for the preparation of intermediates useful in the production of such derivatives (W. Charney and W. L. Herzog-Microbial Transformations of Steroids Handbook - Academic Press, New York 1967). These transformations are normally performed by cultivating appropriate cultural microbial strains which contain carbohydrates and/or other complex substrates as a source of carbon and of energy. Web site: http://www.delphion.com/details?pn=US04273872__ •
Method for use of 11-lower alkyl steroids Inventor(s): Short; George E. (Arlington Heights, IL) Assignee(s): G. D. Searle & Co. (Chicago, IL) Patent Number: 3,941,880 Date filed: September 16, 1974 Abstract: The method of controlling estrus and ovulation in female bovines by the administration of 11-lower alkyl steroids and 11-lower alkyl steroid compositions for use therein.Drug delivery system for the controlled elution of 11-lower alkyl steroids comprising the steroid adsorbed in a copolymer of a monoester of an olefinic acid and a diester of an oelfinic acid. The method of controlling estrus and ovulation in female bovines by the implantation of said drug delivery system in the bovines, followed by removal at a predetermined period, alternatively augmenting the estrus response by administration of an estrogenic compound. Excerpt(s): This invention relates to compositions useful in treating female bovines with certain progestational steroids possessing an 11-lower alkyl substituent to attain control of estrus and ovulation and to methods of accomplishing said treatment. Such controlled estrus and ovulation is particularly useful in the course of breeding such farm animals for commercial purposes, for effecting contraception and for producing an anabolic response associated with the inhibition of estrus. As an embodiment of this invention is also provided a novel drug delivery system comprising an 11-lower alkyl steroid, having progestational properties but being essentially devoid of estrogenic activity, adsorbed in a copolymer of a major amount of a monoester of an acrylic or methacrylic acid and a minor amount of a diester of one of said acids which diester serves as a cross-linking agent, each monomer component being chosen such that the resultant copolymer contains at least one free hydroxy group. These polymers per se and their manner of manufacture are generally described in U.S. Pat. Nos. 2,976,576 and 3,220,960, except that in the most preferred embodiment of this invention an aqueous solution is not used in the polymerization so that an anhydrous polymer is prepared instead of the hydrogels of U.S. Pat. Nos. 2,976,576 and 3,220,960. A further significant distinction lies in the fact that the steroid is added to the monomer mixture prior to polymerization in accordance with methods disclosed in the literature, suitably by the methods described in U.S. Pat. No. 2,721,871. Progestational steroids have been administered to domestic animals orally, parenterally and intravaginally for various
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purposes, including the control of estrus and ovulation. One purpose of such control is to attain near simultaneous release of estrus and ovulation in large numbers of cycling animals following cessation of treatment (i.e., synchronization of estrus and ovulation), thus facilitating controlled breeding for commercial purposes, e.g., breeding by artificial insemination, natural service or hand service. Other important commercial purposes of such control are: (1) to aid in the induction of ovulation in acyclic animals, such as animals which have recently borne young so that such animals with long gestation periods have greater assurance of producing an offspring each year; (2) to aid in the induction of ovulation in animals that are near but have not reached puberty; and (3) to aid in the induction of fertile ovulation in animals with impaired fertility resulting from neurohormonal imbalances or deficiencies resulting in failure to cycle. Moreover such control can enable long term, suitably 90-180 days, contraception in female range bovines. Such control can also be employed for inhibition of estrus in feed lot heifers. Web site: http://www.delphion.com/details?pn=US03941880__ •
Method of altering hypothalamic function by nasal administration of estrene steroids Inventor(s): Berliner; David L. (Atherton, CA), Adams; Nathan William (Salt Lake City, UT), Jennings-White; Clive L. (Salt Lake City, UT) Assignee(s): Pherin Corporation (Menlo Park, CA) Patent Number: 5,783,571 Date filed: September 28, 1993 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human semiochemical, e.g. an Estrene steroid, or a pharmaceutical composition containing an Estrene steroid, such that the ligand semiochemical binds to a specific neuroepithelial receptor. The steroid is preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): Finally, this application may relate to a co-pending U.S. patent application entitled "Fragrance Compositions Containing Human Pheromones", filed 24 Mar. 1992, U.S. Ser. No. 07/856,435. This invention relates generally to pharmaceutical compositions and methods for effectuating change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals. More particularly, the invention relates to the use of certain Estrene steroids as neurochemical effectuators of physiology and behavior. The present invention relates to certain compounds, namely Estrene steroids and related compounds as will be described herein, and methods of using these compounds as human semiochemicals in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g. the reduction of anxiety. Estrene steroids are typified by 17.beta.Estradiol (1,3,5(10)-Estratriene-3,17.beta.-diol), and are characterized by a phenolic 1,3,5(10) A-ring and a hydroxy or hydroxy derivative, such as an ether or ester, at the 3position. The pheromone properties of some Estrene steroids for some mammalian species has been described. Michael, R. P. et al., Nature (1968) 218:746 refers to Estrogens (particularly Estradiol) as a pheromonal attractant of male rhesus monkeys. Parrot, R. F., Hormones and Behavior (1976) 7:207-215, reports Estradiol benzoate injection induces mating behavior in ovariectomized rats; and the role of the blood level of Estradiol in make sexual response (Phoenix, C. H., Physiol. and Behavior (1976) 16:305-310) and female sexual response (Phoenix, C. H., Hormones and Behavior (1977) 8:356-362) in
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Rhesus monkeys has been described. On the other hand, there is little agreement in the literature as to whether or not pheromones as such play any role in the reproductive behavior and interpersonal communication of mammals (Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", In: Mammalian Olfaction, Reproductive Processes, and Behavior, Doty, R. L., Ed., Academic Press, 1976). Web site: http://www.delphion.com/details?pn=US05783571__ •
Method of preparing 11.beta., 17.alpha., 20, 21-tetrahydroxy corresponding 11.beta., 17.alpha., 21-trihydroxy-20-oxo steroids
steroids
and
Inventor(s): Goodhue; Charles T. (Rochester, NY), Kydd; Gwendolyn C. (Rochester, NY), Foster; Charles H. (Kingsport, TN), McCombs; Charles A. (Kingsport, TN) Assignee(s): Eastman Kodak Company (Rochester, NY) Patent Number: 4,588,683 Date filed: February 6, 1984 Abstract: Disclosed herein is a method for preparing 11.beta., 17.alpha., 20, 21tetrahydroxy steroids of the pregnane class. This method comprises incubating the corresponding 17.alpha., 20.alpha. or.beta., 21-trihydroxy steroid in the presence of a culture medium capable of effecting the 11.beta.-hydroxylation, such medium comprising a fungal culture of the genus Curvularia. Also disclosed herein is a method for preparing 11.beta., 17.alpha., 21-trihydroxy-20-oxo steroids of the pregnane class. This method comprises the hydroxylation method described hereinabove followed by conversion of the resulting 11.beta., 17.alpha., 20.alpha. or.beta., 21-tetrahydroxy steroid into the corresponding 11.beta., 17.alpha., 21-trihydroxy-20-oxo steroid. Excerpt(s): The present invention relates to a method of preparing 11.beta.-hydroxy steroids. In particular, it relates to microbiological methods of preparing 11.beta., 17.alpha., 20, 21-tetrahydroxy steroids and the corresponding 11.beta., 17.alpha., 21trihydroxy-20-oxo steroids. It is well known that 11.beta.-hydroxy steroids exhibit antiinflammatory activity. For example, hydrocortisone is an effective therapeutic agent for the treatment of rheumatoid arthritis and other inflammatory diseases. Such steroids, including cortisone, prednisolone, dexamethasone, betamethasone, prednylidene and flurandrenolone, can be produced from naturally occurring steroids by means of expensive, multistage synthesis. An intensive research effort has been ongoing over many years to find methods for making 11.beta.-hydroxy steroids using either chemical or microbiological techniques. The most difficult step in the synthesis of such compounds is the stereospecific introduction of the hydroxyl group at the C-11 position of the steroid molecule. Web site: http://www.delphion.com/details?pn=US04588683__ •
Method of preparing 16.alpha., 17.alpha.-dialkylated steroids Inventor(s): Conrow; Raymond E. (Crowley, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 6,040,468 Date filed: November 5, 1998
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Abstract: 16.alpha., 17.alpha.-dialkylated steroids are prepared by reacting a 16.alpha.alkyl-17(20)-enyl-20-silyl ether with an alkylating agent and an enol silyl ether cleaving agent in a suitable solvent. Excerpt(s): The present invention relates to methods of synthesizing 16.alpha., 17.alpha.dialkylated steroids. In particular, the present invention relates to methods of appending a 17.alpha.-alkyl substituent to a steroidal 16.alpha.-alkyl-17(20)-enyl-20-silyl ether. 16.alpha., 17.alpha.-dialkylated steroids have desirable medicinal properties. See, for example, U.S. Pat. No. 4,686,214; Cairns, et al., J. Chem. Soc., Perkin Trans. I, 1981:2306, and references cited therein. Previous syntheses of 16.alpha., 17.alpha.dialkylated steroids have employed a one-step conjugate addition-enolate trapping method to accomplish the addition of the C16 and C17 alkyl groups. For example, see Schaub, et al., J. Med. Chem., 10:789 (1967), and Cairns, et al., J. Chem. Soc., Perkin Trans. I, 1978:1594 and 1976:1558, disclosing alkyl Grignard conjugate addition reaction followed by an alkyl halide quench in a single reaction vessel. Web site: http://www.delphion.com/details?pn=US06040468__ •
Method of preparing 9.beta., 10.alpha.-5,7-diene steroids Inventor(s): Rappoldt; Menso P. (Weesp, NL), Mos; Gerardus H. M. (Weesp, NL) Assignee(s): Duphar International Research B.V. (Weesp, NL) Patent Number: 4,601,855 Date filed: February 12, 1985 Abstract: The invention relates to the preparation of 9.beta.,10.alpha.-5,7-diene steroids by irradiating the corresponding 9.alpha.,10.beta. steroids with filtered ultraviolet light of an antimony lamp. Excerpt(s): The invention relates to a method of preparing 9.beta.,10.alpha.-5,7-diene steroids by irradiating the corresponding 9.alpha.,10.beta.-steroids with filtered ultraviolet light. 9.beta.,10.alpha.-5,7-diene steroids generally are intermediates in the synthesis of pharmacologically interesting compounds which can fulfil a useful function in the human body. The hormone-analogue 6-dehydro-9.beta.,10.alpha.-progesterone (9.beta.,10.alpha.-pregna-4,6-diene-3,20-dione) or dydrogesterone is an orally active progestative hormone and is generally used to correct deficiencies of progesterone in the body. Therefore, a good possibility for synthesizing this substance and other 9.beta.,10.alpha.-steroids from available or readily available raw materials is of great importance. Various 9.alpha., 10.beta.-steroids, for example, ergosterol, pregnenolone and 7-dehydrocholesterol, are available as raw materials for the preparation of 9.beta., 10.alpha.-5, 7-diene steroids. The preparation of dydrogesterone from pregnenolone is described by Rappoldt et al. in Recueil trav. chim. 80,43 (1961) and 90, 27 (1971). Important intermediates in the synthesis of dydrogesterone are lumisterol.sub.2, 3(ethylenedioxy)-9.beta.,10.alpha.-pregna-5,7-diene-20-one and 3,20-bis(ethylenedioxy)9.beta.,10.alpha.-pregna-5,7-diene. These intermediates can be prepared by irradiating the corresponding 9.alpha.,10.beta.-isomers, namely ergosterol, 3-(ethylenedioxy)9.alpha.,10.beta.-pregna-5,7-diene-20-one and 3,20-bis(ethylenedioxy)-9.alpha.,10.beta.pregna-5,7-diene, respectively, with ultraviolet light. This irradiation is preferably carried out with filtered ultraviolet light. A high-pressure mercury lamp has so far been used for this purpose. In the above-mentioned publications, the desired 9.beta.,10.beta.5,7-diene steroids were formed during this photochemical isomerisation in yields of only 20% calculated on converted 9.alpha.,10.beta.-isomer. When the UV-irradiation was
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carried out in two steps, namely first by means of short-wave and then by means of long-wave UV-radiation as described in Netherlands Patent Specification 112,521, the desired 9.beta.,10.alpha.-5,7-diene steroid could also be isolated only in a yield of not yet 20% calculated or converted starting material. Obviously, a considerable part of the expensive starting material is lost in this photochemical isomerisation probably due to the formation of undesired side products. It therefore stands to reason that an improvement of the yield in this photochemical conversion is of great importance. Web site: http://www.delphion.com/details?pn=US04601855__ •
Method of treatment using mouthwashes containing steroids and antifungal agents and compositions of matter Inventor(s): Eisen; Drore (6720 E. Beechlands Dr., Cincinnati, OH 65237) Assignee(s): none reported Patent Number: 5,310,545 Date filed: January 15, 1993 Abstract: Compositions used to treat inflammatory diseases of the mouth contain antiinflammatory steroids in combination with antifungal drugs in an aqueous medium as a mouthwash. Swishing for three to five minutes, then expectorating the mouthwashes results in maintenance of contact of the active agents with the oral cavity surfaces for a longer time than would application of gels containing those agents. The mode of application is simple and is not repugnant to the patient as is the application of creams, gels, or ointments. Excerpt(s): The invention is related to treatment of inflammatory diseases of the mouth using anti-inflammatory steroids in combination with antifungal drugs in an aqueous medium as a mouthwash. The treatment of inflammatory diseases of the mouth is difficult. Patients so afflicted often require treatment with agents that are potentially toxic when given systemically to control the disease activity. Moreover, diseases such as oral lichen planus, pemphigus, pemphigoid, aphthous stomatitis, erythema multiforme, and idiopathic stomatitis are disorders in which spontaneous remissions are rare. Means of treating such diseases without undue exposure of the patient to systemic effects of powerful therapeutic agents is desirable. Treatment with topical corticosteroids as presently formulated and administered has significant limitations. Existing commercially available compositions are usually supplied as creams, gels, or ointments that are intended for cutaneous applications. Such preparations are not readily acceptable to patients for use on the mucosa. The prior art compositions must be applied frequently (up to six times a day). Furthermore, the compositions are not readily applied to the areas of the oral cavity that are difficult to reach. Furthermore, treatment with steroids causes increased susceptibility to fungal infections of the mouth. This complication is especially common in patients suffering from oral lichen planus, a condition in which Candida is found to colonize mouth lesions in 25% of the patients. Web site: http://www.delphion.com/details?pn=US05310545__
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Method of using 4-amino-.DELTA.sup.4 -steroids in the treatment of benign prostatic hyperplasia Inventor(s): Weintraub; Philip M. (Cincinnati, OH), Burkhart; Joseph P. (West Chester, OH), Blohm; Thomas R. (Madeira, OH) Assignee(s): Merrell Dow Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 5,436,237 Date filed: February 25, 1994 Abstract: The present invention relates to 4-amino-.DELTA.sup.4 -steroids which are useful as inhibitors of 5.alpha.-reductase. The compounds are prepared by the reaction of an appropriate 4-azido steroid with triphenylphosphine in an aqueous inert solvent with heating. Excerpt(s): Mammalian steroid 5.alpha.-reductase, an enzyme present in mammalian tissues including skin, male genitalia and prostate gland, catalyzes the conversion of the steroidal hormone testosterone to the steroidal hormone dihydrotestosterone (17.beta.hydroxy-5.alpha.-androstan-3-one). Testosterone and dihydrotestosterone (DHT) are both androgenic hormones and they are the primary androgenic steroids in males. These steroids are responsible for the physical characteristics which differentiate males from females. DHT, however, is much more potent than testosterone as an androgen and it acts as an end-organ effector in certain tissues, particularly in mediating growth. Furthermore, the formation of DHT occurs primarily in the target cells themselves as a result of the reduction of testosterone by 5.alpha.-reductase. It is known that skin responds to androgens and is an active site of androgen metabolism. In particular, testosterone is converted to DHT in the skin by the action of 5.alpha.-reductase. Testosterone metabolism in the skin may at times be abnormally excessive and have undesirable effects as a result of the DHT formed. Thus, there is considerable evidence that DHT is involved in the pathogenesis of acne, including acne vulgaris, as well as other androgen associated conditions [See Price, Arch. Dermatol. 111, 1496 (1975)]. Agents which are capable of blocking the formation of DHT from testosterone in skin, such as by inhibiting the activity of 5.alpha.-reductase, would therefore be useful in the treatment of acne. In addition, other physical conditions and disease states, including benign prostatic hypertrophy, androgenic alopecia (common baldness caused by androgen in genetically susceptible men and women), seborrhea and female hirsutism, are also associated with elevated androgen activity and could be treated by the administration of 5.alpha.-reductase inhibitors. [See T. Liang et al., Endocrinology 117, 571 (1985); J. R. Brooks et al., Steroids 47, 1 (1986); J. R. Carlin et al., Journal Of Chromatography, 427, 79 (1988).] Thus, agents which are capable of blocking the formation of DHT from testosterone by inhibiting the effects of 5.alpha.-reductase would also be effective in the treatment of these conditions. Web site: http://www.delphion.com/details?pn=US05436237__
Patents 363
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Methods and compositions using.DELTA.sup.16 unsaturated C.sub.17 heterocyclic steroids useful as steroid C.sub.17-20 lyase inhibitors Inventor(s): Peet; Norton P. (Cincinnati, OH), Burkhart; Joseph P. (Plainfield, IN), Gates; Cynthia A. (Fairfield, OH) Assignee(s): Merrell Pharmaceuticals Inc. (Bridgewater, NJ) Patent Number: 5,977,094 Date filed: May 6, 1998 Abstract: The present invention relates to methods and compositions using.DELTA.sup.16 unsaturated steroids which are useful as steroid C.sub.17-20 lyase inhibitors. Excerpt(s): It is estimated that 75% of prostatic cancers are sensitive to levels of androgens, more specifically testosterone. (Van Wauwe, J. P. and Janssen, P. A. J., J. Med. Chem., (1989), 32, 2233). It is well established that reduction of serum testosterone levels is useful in the treatment of such prostatic cancers. In clinical practice, this has been accomplished for example by orchiectomy or by diethylstilbestrol treatment. However, the first approach is often psychologically unacceptable while a number of side effects are associated with the second approach. The cytochrome P450.sub.17.alpha. monooxygenase enzyme system catalyzes the 17.alpha.-hydroxylation of C.sub.21 steroids and also catalyzes the oxidative cleavage of the C.sub.17-20 bond. (Blohm, T. R. et al., Biochem. Biophys. Res. Commun., (1989), 162, 1571). More specifically the steroid C.sub.17-20 lyase activity of cytochrome P-450.sub.17.alpha. catalyzes the conversion of the C.sub.21 steroids pregnenolone and progesterone to the C.sub.19 steroids dehydroepiandrosterone and androstenedione, which are the precursors of the androgens, 5.alpha.-dihydrotestosterone and testosterone. Androstenedione and testosterone, in turn, are the precursors of the estrogens, estrone and estradiol. Thus, inhibition of the steroid C.sub.17-20 lyase can reduce formation of the androgens as well as the estrogens. As a result of this effect, the search for effective and selective inhibitors of the steroid C.sub.17-20 lyase enzyme is expanding. (Laughton, C. A. and Neidle, S., Biochem. Biophys. Res. Commun., (1990), 171, 1160). C.sub.17-20 lyase inhibitors would be useful for treating various androgen-dependent disorders. More particularly, such compounds would be useful in the treatment of prostatic carcinoma, benign prostatic hyperplasia, male-pattern baldness and virilism and hirsutism (in women). In addition, C.sub.17-20 lyase inhibitors would also be useful in the treatment of estrogen-dependent disorders, such as estrogen dependent breast cancer. Thus, in light of the drawbacks associated with diethylstilbestrol treatment or orchiectomy, there has been an ongoing search for effective inhibitors of steroid C.sub.17-20 lyase. The present invention relates to C.sub.17 heterocyclic steroids and also to a method for using such compounds as effective steroid C.sub.17-20 lyase inhibitors. More particularly, the present invention relates to the treatment of androgen dependent disorders. Web site: http://www.delphion.com/details?pn=US05977094__
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Methods for controlling ocular hypertension with angiostatic steroids Inventor(s): Clark; Abbot F. (Arlington, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 4,876,250 Date filed: October 31, 1988 Abstract: Angiostatic steroids for use in controlling ocular hypertension are disclosed. Pharmaceutical composition of the angiostatic steroids and methods for their use in treating ocular hypertension, including controlling the ocular hypertension associated with primary open angle glaucoma, are disclosed. Excerpt(s): This invention relates to methods and compositions for controlling ocular hypertension. Specifically, the invention is directed to pharmaceutical compositions comprising angiostatic steroids and methods of treatment comprising administering these compositions to treat ocular hypertension, including controlling ocular hypertension associated with primary open angle glaucoma. Steroids functioning to inhibit angiogenesis in the presence of heparin or specific heparin fragments are disclosed in Crum, et al., A New Class of Steroids Inhibits Angiogenesis in the Presence of Heparin or a Heparin Fragment, Science, Vol. 230, pp. 1375-1378 (Dec. 20, 1985). The authors refer to such steroids as "angiostatic" steroids. Included within the new class of steroids found to be angiostatic are the dihydro and tetrahydro metabolites of cortisol and cortexolone. In a follow-up study directed to testing a hypothesis as to the mechanism by which the steroids inhibit angiogenesis, it was shown that heparin/angiostatic steroid compositions cause dissolution of the basement membrane scaffolding to which anchorage dependent endothelia are attached resulting in capillary involution; see, Ingber, et al., A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids: Induction of Capillary Basement Membrane Dissolution, Endocrinology 119, pp. 1768-1775 (1986). A group of tetrahydro steroids useful in inhibiting angiogenesis is disclosed in International Patent Application No. PCT/US86/02189, Aristoff, et al., (The UpJohn Company). The compounds are disclosed for use in treating head trauma, spinal trauma, septic or traumatic shock, stroke and hemorrhage shock. In addition, the patent application discusses the utility of these compounds in embryo implantation and in the treatment of cancer, arthritis and arteriosclerosis. The compounds are not disclosed for ophthalmic use. Web site: http://www.delphion.com/details?pn=US04876250__
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Methods of inhibiting angiogenesis and tumor growth, and treating ophthalmologic conditions with angiostatic and therapeutic steroids Inventor(s): Petrow; Vladimir (Chapel Hill, NC), Proia; Alan D. (Durham, NC) Assignee(s): Duke University (Durham, NC) Patent Number: 5,646,136 Date filed: January 4, 1994 Abstract: Methods for treating angiogenesis, tumors, and ocular hypertension with steroids are disclosed herein. The steroids have angiostatic activity with reduced glucocorticoid activity. Excerpt(s): This invention relates generally to methods of inhibiting angiogenesis and tumor growth and treating ophthalmological conditions, and more specifically relates to
Patents 365
methods of doing so through the administration of steroidal compounds. The development of new capillary blood vessels, also known as angiogenesis, occurs in normal bodily processes such as healing of wounds, growth of organs such as the corpus luteum, and growth of the embryo. Angiogenesis is also a characteristic that links many diverse diseases. See Maugh II, Science 212: 1374-1375 (1981); Auerback, Lymphokines 4: 69-68 (1981). It is a major component of some ophthalmological pathologies such as corneal graft rejection, corneal neovascularization following injury or infection, diabetic retinopathy, retrolental fibroplasia and neovascular glaucoma, Garner, Int. Rev. Exp. Pathol 28: 249-307 (1986), and is also a major factor in many ulcerative diseases such as rheumatoid arthritis, ulcerative colitis, and gastric ulcer. In addition, angiogenesis is a major component in pathological but nonmalignant conditions such as hemangioma, angiofibroma of the nasopharynx, avascular necrosis of bone, and psoriasis, and is further an essential requirement for tumor growth and metastasis, See, e.g., Folkman, J. Natl. Cancer Inst. 82: 4-6 (1990); Weidner et al., New Engl. J. Med. 324: 1-8 (1991). Although originally developed for their anti-inflammatory properties, glucocorticoids are now recognized to have a wide variety of therapeutic uses. For example, many steroids with anti-inflammatory activity inhibit angiogenesis. In particular, steroids possessing the glucocorticoid side chain have been shown to inhibit angiogenesis, both alone and in conjunction with heparin, heparin fragments, or water-soluble cyclodextrin sulphate salts. See, e.g., Folkman et al., U.S. Pat. No. 5,019,562 (1991); Braughler et al., U.S. Pat. No. 4,772,042 (1988); Folkman et al., Ann. Surg. 206: 374-3883 (1987). Web site: http://www.delphion.com/details?pn=US05646136__ •
Methylation of de-A steroids Inventor(s): Buchschacher; Paul (Arlesheim, CH), Furst; Andor (Basel, CH), Labler; Ludwig (Allschwil, CH), Meier; Werner (Bottmingen, CH), Scott; John William (Upper Montclair, NJ) Assignee(s): Hoffmann-La Roche, Inc. (Nutley, NJ) Patent Number: 4,087,436 Date filed: June 23, 1975 Abstract: Treatment of de-A steroids with a methylation agent at extremely low temperatures, i.e., below -50.degree. C. produces corresponding 10.beta.-methyl.DELTA.sup.9(11) -deA steroids with a high 10.beta. to 10.alpha. isomer ratio. A number of the product 10.beta.-methyl-.DELTA.sup.9(11) -deA steroids are novel compounds. They are useful as intermediates in the synthesis of known medicinally valuable steroids. Excerpt(s): German Patent No. 1,196,193 dated July 8, 1965 discloses the alkylation of a 17.beta.-acyloxy-3,5-diketo-4,5-seco-19-nor-.DELTA.sup.9 -androstene, which is selectively ketalized in the 3-position, by means of a lower molecular weight alkylation agent in the presence of an alkali metal tert.-alcoholate to yield in a stereospecific reaction only the corresponding 10.beta.-compound. A subsequent study [J. E. McMurry, Ph.D. Thesis, Columbia University, New York, (1967)] was unable to confirm this statement. On the contrary, under various reaction conditions, including those given in the aforementioned Patent Specification, there was obtained a mixture of 10.beta.:10.alpha.-compounds in the proportion 2:1. It has unexpectedly been found that when the aforesaid process is carried out at the indicated low temperatures that the 10.beta.:10.alpha.-proportion in the resulting product of formula I is 4:1 or even greater.
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Most preferably the process of this invention is conducted at a temperature in the range of from about -70.degree. C. to about -110.degree. C. Web site: http://www.delphion.com/details?pn=US04087436__ •
Microbial process for 9.alpha.-hydroxylation of steroids Inventor(s): Marsheck; William J. (Mentor, OH), Jiu; James (Morton Grove, IL), Wang; Ping T. (Louisville, KY) Assignee(s): G. D. Searle & Co. (Skokie, IL) Patent Number: 4,397,947 Date filed: June 12, 1981 Abstract: Valuable 9.alpha.-hydroxy steroids are prepared via microbial enzymatic oxidation (MEO) by conventional fermentation means, without the need for a.DELTA.sup.1 dehydrogenation inhibitor, utilizing novel microorganism Nocardia canicruria ATCC 31548. Also disclosed is a novel method using any.DELTA.sup.1 dehydrogenase producing organism and a novel bio-reactor technique means for preparing said steroids. Excerpt(s): The present invention provides a process for preparing 9.alpha.-hydroxy steroids by the microbial enzymatic oxidation (MEO) of steroids which are unsubstituted at the 9 position. It also provides novel microorganism Nocardia canicruria ATCC 31548. The invention further relates to a process for preparing 9.alpha.hydroxy steroids using novel bio-reactor technique means. Many useful 9.alpha.hydroxy steroids are known displaying a wide range of activities. The 9.alpha.-hydroxy steroids of the pregnane series have glucocorticoid and progestational activity. The 9.alpha.-hydroxy compounds of the androstane series are useful as antiandrogenic, antiestrogenic and antifertility agents. These 9.alpha.-hydroxy steroids are also useful steroids. For example, the 9.alpha.-hydroxy-11 unsubstituted steroids can be easily dehydrated to the valuable 9(11)-dehydro steroids in accordance with methods known in the art e.g., with thionyl chloride in the presence of pyridine. The 9(11)-dehydro compounds thus obtained are known intermediates in the production of highly active compounds. For example, the 9(11)-dehydro steroids can be easily converted to be corresponding 9.alpha.-halo-11.beta.-hydroxy compounds in accordance with procedures known in the art e.g., U.S. Pat. No. 2,852,511 for the preparation of 9.alpha.halo-hydrocortisones. Methods for 9.alpha.-hydroxylation of steroids are known. Yields are in general poor and the steroid to be hydroxylated must be soluble in water to be used in a fermentation process. Web site: http://www.delphion.com/details?pn=US04397947__
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Microbiological preparation of 9-alpha-hydroxy-17-keto steroids Inventor(s): Slijkhuis; Harmen (AE Berkel En Rodenrijs, NL), Marx; Arthur F. (GM Delft, NL) Assignee(s): Gist-Brocades N.V. (Delft, NL) Patent Number: 5,166,055 Date filed: July 15, 1991
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Abstract: 9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86.Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield.The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids. Excerpt(s): The invention relates to a process for the preparation of 9.alpha.-hydroxy-17keto steroids using a new microorganism of the genus Mycobacterium. It is well known that steroid molecules can be transformed by microorganisms (W. Charney, H. L. Herzog, Microbial Transformations of Steroids). Many processes using microbiological transformations of steroids have been developed, to replace cumbersome and expensive chemical processes. A cheap source for the preparation of useful steroid intermediates are the abundantly available sterols, for example cholesterol and sitosterol. Microorganisms have been selected which are able to use these steroids as a carbon source. In several patent publications, e.g. Dutch patent applications NL 6513718 and NL 6705450, the microbiological degradation of the C-17-side chain with the preservation of the steroid nucleus is described. With specific inhibitor compounds and later also with specially developed mutants, as described in U.S. Pat. Nos. 3,684,657, 3,759,791 or 4,345,029, it was possible to obtain in high yield androst-4-ene-3,17-dione and androsta-1,4-diene-3,17- dione, which are starting compounds for the synthesis of therapeutically useful steroids. Among the microbiologically prepared steroids 9.alpha.hydroxy-17-keto steroids are important because they are valuable starting compounds for the preparation of corticosteroids (J. Org. Chem. (1979) 44, 1582). The necessary introduction in prospective corticosteroids of a hydroxyl group on C-11 and optionally of a halogen atom on C-9 can be carried out by easy, well established chemical reactions, departing from this class of compounds. Web site: http://www.delphion.com/details?pn=US05166055__ •
Nitrosated and nitrosylated steroids compositions, and methods for treating respiratory disorders Inventor(s): Garvey; David S. (Waltham, MA), Letts; L. Gordon (Dover, MA), Renfroe; H. Burt (Wellesley, MA), Richardson; Stewart K. (Ashford, CT) Assignee(s): NitroMed, Inc. (Bedford, MA) Patent Number: 6,197,762 Date filed: September 18, 1998 Abstract: Disclosed are (i) compounds of a steroid, a.beta.-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO.sub.2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids,.beta.-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO.sub.2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO.sup.+) or nitroxyl (NO.sup.-), or as the neutral species, nitric oxide (NO.cndot.) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
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Excerpt(s): The present invention relates to the field of compounds, compositions and uses therefore, in oral and/or nasal administration prophylaxis and/or treatment of respiratory disorders. More particularly the invention relates to nitrosated and nitrosylated compounds, compositions comprising such compounds, which can optionally be unsubstituted or substituted with at least one NO or NO.sub.2 moiety, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO), or as the neutral species, nitric oxide (NO.cndot.); and uses for each of them. A broad spectrum of respiratory diseases and disorders have been recognized, many of which have overlapping and interacting etiologies. One of the most widespread and prevalent of these diseases in western populations is the chronic disease referred to as "asthma". Other such disorders are also characterized by acute pulmonary vasoconstriction such as may result from pneumonia, traumatic injury, aspiration or inhalation injury, fat embolism in the lung, acidosis inflammation of the lung, adult respiratory distress syndrome, acute pulmonary edema, acute mountain sickness, post-cardiac surgery, acute pulmonary hypertension, persistent pulmonary hypertension of the newborn, perinatal aspiration syndrome, hyaline membrane disease, acute pulmonary thromboembolism, herapin-protamine reactions, sepsis, status asthmaticus or hypoxia (including iatrogenic hypoxia) and other forms of reversible pulmonary vasoconstriction. Such pulmonary disorders also are also characterized by inflammation of the lung including those associated with the migration into the lung of non-resident cell types including the various leucocyte subclasses. Also included in the respiratory disorders contemplated are cystic fibrosis and other diseases which are characterized by excess mucosal secretion. Other physiological events which are contemplated to be controlled include platelet activation in the lung. Asthma is a major and disabling obstructive respiratory disease associated with significant morbidity and mortality. The term "asthma" has been used to describe a condition which is characterized by widespread fluctuations in the diameter or caliber of bronchial airways over short periods of time resulting in changes in lung function. The resulting increased resistance to air flow produces symptoms including breathlessness (dyspnea), chest constriction or "tightness" and wheeze. The term as used is not currently limited to a disorder or disease resulting from any specific cause or causes, rather it is characterized by its clinical manifestation. A true immunological mechanism may or may not be a factor in the etiology of an individual asthmatic condition. Further, characteristic wheezing may not be present in particularly severe attacks where transport of air is completely obstructed. Regardless of the cause, asthma in all sufferers is characterized by reversible hyperresponsiveness of tracheal bronchial smooth muscle resulting in its contraction and interference with normal respiration. The lungs of patients who die of asthma are usually pale pink, hyperinflated, and fail to collapse after their removal from the chest. Many of the airways throughout the bronchial tree are occluded by thick mucus plugs which are infiltrated with various types of leukocytes, including mast cells. The smooth muscle of the airways is hypertrophied. The bronchoconstriction or bronchospasm characterized by asthmatic attacks causes obstruction to air flow which necessitates a forced exhalation and maintenance of artificially elevated functional air reserve capacity to keep the airways open. The resultant lung hyperinflation places a significant stress on the cardiovascular system (particularly the right ventricle) which can lead to a consequent cardiovascular event. One possible result is a progressive decrease in cardiac output referred to as "cardiopulmonary tamponade". Most deaths resulting from asthma are caused by a condition referred to as "status asthmaticus," which is essentially an intensely severe and bronchospasm that is unresponsive to treatment. Web site: http://www.delphion.com/details?pn=US06197762__
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Novel enol esters of steroids, compositions containing such compounds, processes for their preparation and methods of treatment therewith Inventor(s): Fex; Hans (Helsingborg, SE), Hansen; Bertil (Helsingborg, SE), Holmberg; Krister (Angelholm, SE), Hogberg; Bertil (Helsingborg, SE), Konyves; Imre (Helsingborg, SE) Assignee(s): Aktiebolaget Leo (SE) Patent Number: 4,150,126 Date filed: January 17, 1977 Abstract: This invention relates to novel enol esters of steroids having an antitumor activity and to the preparation thereof. The invention is also concerned with pharmaceutical compositions containing the said compounds and methods of treatment therewith. Excerpt(s): This invention relates to novel enol esters of steroids, having an antitumour activity, and to the preparation thereof. The invention is also concerned with pharmaceutical compositions containing the said compounds and methods of treatment therewith. Certain carboxylic acids containing a phenyl group substituted with a bis(2chloroethyl)amino group are well-known antitumour agents. By reaction of such acids with steroids, having readily esterifiable hydroxyl groups, carboxylic esters have been obtained which, in addition to the antitumour effect exerted by the acid part, may possess valuable hormonal activities, derived from the steroid part. Such esters are described in e.g. J. Med. Chem. 11 (1968) 1106, ibid 12 (1969) 810, ibid 15 (1972) 1158, and U.S. Pat. No. 3,732,260. Web site: http://www.delphion.com/details?pn=US04150126__
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Pharmaceutical compositions containing dehydroepiandrosterone and anesthetic steroids in the treatment of arthritis and other joint disabilities
other
Inventor(s): Peat; Raymond F. (P.O. Box 3427, Eugene, OR 97403) Assignee(s): none reported Patent Number: 4,628,052 Date filed: May 28, 1985 Abstract: The present invention is concerned with compositions and methods of treating rheumatoid arthritis, osteoarthritis, and arthritis associated with psoriasis and with lupus and other auto-immune diseases, and also for treating non-specific joint pain associated with stress or incidental to another ailment, using dehydroepiandrosterone and/or other anesthetic steroids dissolved in an oily vehicle, and preferably administered topically or orally. Excerpt(s): This invention is concerned with compositions and methods of treating rheumatoid arthritis, osteo-arthritis, and arthritis associated with psoriasis and with lupus and other auto-immune diseases, and also for treating non-specific joint pain associated with stress or incidental to another ailment, using dehydroepiandrosterone (DHEA) and/or other anesthetic steroids dissolved in an oily vehicle, and preferably administered topically or orally. The extensive use of cortisone and related antiinflammatory steroids in treating arthritis has been limited by the knowledge of several
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side effects, including calcium loss and osteoporosis, immune suppression, and atrophy of various tissues, including the adrenal glands. Nonsteroidal anti-inflammatory agents have been used with some success to avoid the glucocorticoids' side effects, but generally are ineffective in preventing the advance of the disease process. Other agents have been used or proposed which retard the advance of the disease, possibly by inhibiting mitosis, but they generally have toxic side effects. It would be desirable to use in treatment substances which are normally present in the body at high levels, since these normal substances, especially when used in physiological quantities, rarely have harmful side effects. Web site: http://www.delphion.com/details?pn=US04628052__ •
Phenylpiperazinyl steroids Inventor(s): McCall; John M. (Kalamazoo, MI), Jacobsen; E. Jon (Plainwell, MI), VanDoornik; Frederick J. (Hamilton, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 5,380,839 Date filed: December 1, 1992 Abstract: Disclosed are amino substituted steroids (XI) which contain a phenylpiperazinyl group attached to the terminal carbon atoms of the C.sub.17 -side chain, which are useful as pharmaceutical agents for treating a number of conditions. Excerpt(s): The present invention relates to amino substituted steroids which are useful as pharmaceutical agents. Various amino (substituted) steroids are known with the amine substitution on either the steroidal ring system or on the side chain of the D-ring at C.sub.17. U.S. Pat. No. 4,456,602 discloses steroidal 21-esters in which there is an amino function in the non-steroidal portion of the ester. Web site: http://www.delphion.com/details?pn=US05380839__
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Photoconversion of steroids in microreactors Inventor(s): Fehlner; James R. (Salem Township, PA), Firnberg; Dow (Creskill, NJ) Assignee(s): Inrad (Northvale, NJ) Patent Number: 5,543,016 Date filed: May 18, 1992 Abstract: The photoconversion of steroids is carried out in microreactors to yield desired products, while limiting the formation of undesirable byproducts. The steroid reactant is combined with a microreactor such as solid particles having controlled spaces of appropriate size to provide stereochemical control over the reaction. Appropriate catalyst particles include silica and zeolitic material. The reaction can be conducted in a fluidized bed reactor and the formation of undesirable byproducts can be effectively limited. Excerpt(s): The invention relates generally to the photoconversion of steroids on solid catalytic surfaces and more particularly to controlling the stereochemistry of the photoconversion reaction by proper selection of a microreactor. Photochemical isomerization of steroids are important in the industrial synthesis of commercial
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products. For example, the photoisomerization of 7-dehydrocholesterol (7-DHC) yields previtamin D.sub.3, which can be converted by conventional methods, such as by thermal rearrangement, to vitamin D.sub.3. Vitamin D.sub.3 has many important uses. For example, vitamin D.sub.3 can be used as an additive to milk and in animal feeds to prevent rickets. The photoisomerization of steroids is conventionally carried out in solution. The conventional photolysis of 7-dehydrocholesterol initially gives the desired previtamin D.sub.3. However, previtamin D.sub.3 also absorbs light of the same region of the electromagnetic spectrum as does 7-dehydrocholesterol. This leads to a second undesirable photo-induced isomerization in which tachysterol is formed. Web site: http://www.delphion.com/details?pn=US05543016__ •
Pregnane and cholane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods Inventor(s): Jennings-White; Clive L. (Salt Lake City, UT), Berliner; David L. (Atherton, CA), Adams; Nathan William (Salt Lake City, UT) Assignee(s): Pherin Corporation (Menlo Park, CA) Patent Number: 5,994,333 Date filed: August 3, 1995 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human vomeropherin, e.g. a pregnane or cholane steroid, or a pharmaceutical composition containing a vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): This invention relates generally to pharmaceutical compositions and methods for effectuating change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals. More particularly, the invention relates to the use of certain pregnane and cholane steroids as neurochemical effectuators of physiology and behavior. The present invention relates to certain compounds, namely pregnane and cholane steroids, and methods of using these compounds as human vomeropherins in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g., the reduction of anxiety. Pregnane steroids are characterized by a four ring steroidal structure, a methylation at the 13-position and at the 10-position, and ethylation at the 17-position. Pregnenes are a subset of pregnanes and have at least one double bond. Ohloff, G. et al. (Helv. Chim. Acta (1983) 66:192-217), which is incorporated herein by reference, have shown that several steroids (androstenes) have an odor which varies with different isomeric, diastereomeric, and enantiomeric forms. Some members of this group have been reported to act as a pheromone in some mammalian species--for instance, 5.alpha.androst-16-en-3-one and 5.alpha.-androst-16-en-3.alpha.-ol in pigs (Melrose, D. R., et al., Br. vet. J. (1971) 127:497-502). These 16-androstenes produced by the boar induce mating behavior in estrus sows (Claus, et al., Experimentia (1979) 35:1674-1675). Cholane steroids are characterized by a 5-carbon side chain, the 2-pentyl group, at C-17 of the steroid nucleus. Some studies have noted that, in some species, various characteristics of certain 16-androstenes (including 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.Androst-16-en-3-one), such as concentration, metabolism, and localization, are sexually
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dimorphic (Brooksbank et al., J. Endocr. (1972) 52: 239-251; Claus, et al., J. Endocr. (1976) 68:483-484; Kwan, et al., Med. Sci. Res. (1987) 15:1443-1444). For instance, 5.alpha.Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one, as well as Androsta-4,16dien-3-one, have been found at different concentrations in the peripheral blood, saliva and axillary secretions of men and of women (Kwan, T. K., et al., Med. Sci. Res. (1987) 15:1443-1444), and their function as a human pheromone, to the extent of affecting choice and judgment, has been suggested (Id. see also Gower, et al., "The Significance of Odorous Steroids in Axillary Odour", In, Perfumery, pp. 68-72, Van Toller and Dodds, Eds., Chapman and Hall, 1988); Kirk-Smith, D. A., et al., Res. Comm. Psychol. Psychiat. Behav. (1978) 3:379). Androstenol (5.alpha.-androst-16-en-3.alpha.-ol) has been claimed to exhibit a pheromone-like activity in a commercial men's cologne and women's perfume (Andron.TM. for men and Andron.TM. for women by Jovan). Japanese Kokai No. 2295916, refers to perfume compositions containing androstenol and/or its analogues. Androstadien-3.beta.-ol (and perhaps the 3.alpha.-ol) has also been identified in human axillary secretion (Gower, et al., supra, at 57-60). On the other hand, there is little agreement in the literature as to whether or not any putative pheromone actually plays any role in the sexual or reproductive behavior of mammals, particularly of humans. See: Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", In: Mammalian Olfaction, Reproductive Processes and Behavior, Doty, R. L., Ed., Academic Press, 1976). See also: Gower, et al, supra at 68-73. Web site: http://www.delphion.com/details?pn=US05994333__ •
Pregnane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods Inventor(s): Berliner; David L. (Atherton, CA), Jennings-White; Clive L. (Salt Lake City, UT), Adams; Nathan W. (Salt Lake City, UT) Assignee(s): Pherin Corporation (Menlo Park, CA) Patent Number: 5,563,131 Date filed: August 4, 1994 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human vomeropherin, e.g. a pregnane steroid, or a pharmaceutical composition containing a vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): This application is related to U.S. application Ser. No. 08/127,908, filed Sep. 28, 1993 which is a continuation-in-part of U.S. application Ser. No. 07/903,604, filed 24 Jun. 1992, which in turn is a continuation-in-part of U.S. application Ser. No. 07/708,936, filed 31 May 1991, which in turn is a continuation-in-part of U.S. application Ser. No. 07/638,185, filed 7 Jan. 1991, now abandoned. The application also relates to U.S. application Ser. No. 08/127,980 filed Sep. 28, 1993 which is another continuation-in-part of U.S. patent application Ser. No. 07/903,604, U.S. patent application Ser. No. 08/077,359, filed 15 Jun. 1993, and to commonly assigned, co-pending U.S. patent application Ser. No. 07/903,525, filed 24 Jun. 1992 (a continuation-in-part of U.S. application Ser. No. 07/707,862, filed 31 May 1991, which in turn is a continuation-inpart of U.S. application Ser. No. 07/638,743, filed 7 Jan. 1991, now abandoned) entitled
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"Estrene Steroids as Neurochemical Initiators of Change in Human Hypothalamic Function and Related Pharmaceutical Compositions and Methods"; and to the commonly assigned, co-pending continuation-in-part of 07/903,525, U.S. patent application Ser. No. 08/077,140. The aforementioned U.S. patent applications are each incorporated herein by reference. This invention relates generally to pharmaceutical compositions and methods for effectuating change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals. More particularly, the invention relates to the use of certain pregnane steroids as neurochemical effectuators of physiology and behavior. Web site: http://www.delphion.com/details?pn=US05563131__ •
Preparation of 20-keto-.DELTA.sup.16 -steroids Inventor(s): van Leusen; Albert M. (Groningen, NL), van Leusen; Adriaan M. (Winsum, NL) Assignee(s): Gist-Brocades N.V. (Delft, NL) Patent Number: 4,551,278 Date filed: April 27, 1984 Abstract: A novel process for the preparation of 20-keto-.DELTA.sup.16 -steroids comprising reacting a 17-(isocyanosulfonylmethylene)-steroid with an alkylating agent QR.sub.4 wherein R.sub.4 is an organic group and Q is a group or atom readily displaced with a nucleophile to form a 20-isocyano-20-sulfonyl-.DELTA.sup.16 -steroid followed by hydrolysis which are intermediates for the preparation of corticosteroids and the novel intermediates formed therein. Excerpt(s): Steroids are used on a large scale as the active ingredients of many types of pharmaceutical compositions and depending on the substituent pattern of the carbonskeleton, the steroids can be divided into a number of main classes. An important main class of steroids is formed by the cortico-steroids whose natural representatives are usually produced by the adrenal gland. Corticosteroids are characterized by the presence of a 3-keto group, a.DELTA.sup.4 -double bond, an 11.beta.-hydroxy group, a 17.alpha.-hydroxy group and a 17.beta.-hydroxy-acetyl side chain. For a long time, corticosteroids were made by chemical degradation of gall acids as cholic acid, desoxycholic acid and glycocholic acid. Afterwards, hecogenin which could be isolated from plants, particularly from numerous Agave species, became an important raw material too. Since the possibility of the introduction of an 11-hydroxy group by microbiological methods, diosenin which could be isolated from numerous Dioscoreacaea species and stigmasterol, usually isolated from the phytosterol mixture from soya or calabar beans, have become the most important raw material for the preparation of corticosteroids. Much attention has been given to new, cheaper raw materials for the synthesis of pharmaceutically active steroids. Therefore, the degradation of the abundant soya bean derived sterols, sitosterol and campesterol by microbiological methods into 17-oxo-steroids was extensively investigated and as a result thereof, 17-oxo-steroids are readily available now at low prices which makes these compounds, together with the possibility of the introduction of an 11-hydroxy group by microbiological methods, ideal starting materials for corticosteroid synthesis. Web site: http://www.delphion.com/details?pn=US04551278__
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Preparation of 9-.alpha.-hydroxy-17-keto steroids using Mycobacterium species CBS 482.86 Inventor(s): Slijkhuis; Harmen (Berkel En Rodenrijs, NL), Marx; Arthur F. (Delft, NL) Assignee(s): Gist-Brocades NV (Delft, NL) Patent Number: 5,298,398 Date filed: August 6, 1992 Abstract: 9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86. Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield. The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids. Excerpt(s): The invention relates to a process for the preparation of 9.alpha.-hydroxy-17keto steroids using a new microorganism of the genus Mycobacterium. It is well known that steroid molecules can be transformed by microorganisms (W. Charney, H. L. Herzog, Microbial Transformations of Steroids). Many processes using microbiological transformations of steroids have been developed, to replace cumbersome and expensive chemical processes. A cheap source for the preparation of useful steroid intermediates are the abundantly available sterols, for example cholesterol and sitosterol. Microorganisms have been selected which are able to use these steroids as a carbon source. In several patent publications, e.g. Dutch patent applications NL 6513718 and NL 6705450, the microbiological degradation of the C-17-side chain with the preservation of the steroid nucleus is described. With specific inhibitor compounds and later also with specially developed mutants, as described in U.S. Pat. Nos. 3,684,657, 3,759,791 or 4,345,029, it was possible to obtain in high yield androst-4-ene-3,17-dione and androsta-1,4-diene-3,17- dione, which are starting compounds for the synthesis of therapeutically useful steroids. Among the microbiologically prepared steroids 9.alpha.hydroxy-17-keto steroids are important because they are valuable starting compounds for the preparation of corticosteroids (J. Org. Chem. (1979) 44, 1582). The necessary introduction in prospective corticosteroids of a hydroxyl group on C-11 and optionally of a halogen atom on C-9 can be carried out by easy, well established chemical reactions, departing from this class of compounds. Web site: http://www.delphion.com/details?pn=US05298398__
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Preventing and treating elevated intraocular pressure associated with administered or endogenous steroids using non-steroidal cyclooxygenase inhibitors Inventor(s): Polansky; Jon R. (Mill Valley, CA), Bloom; Ernest (Alamo, CA), Fauss; Donald J. (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,474,985 Date filed: December 22, 1993 Abstract: Methods and compositions for preventing or treating non-inflammatory elevated intraocular pressure associated with administered or endogenous steroids including administering to a mammalian organism a composition including (a) an
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ophthalmologically effective amount of a non-steroidal cyclooxygenase inhibitor, and (b) a pharmaceutically acceptable carrier, to reduce or prevent an elevation of intraocular pressure and/or protein marker induction induced by chronic exposure to glucocorticoids. Excerpt(s): This invention relates to methods for the prevention and treatment of elevated intraocular pressure which is a factor involved in developing optic nerve damage and loss of vision. More particularly, this invention relates to new methods for treating the eye with non-steroidal cyclooxygenase inhibitors (or non-steroidal antiinflammatory, NSAI, agents) to prevent or treat elevated intraocular pressure due to administered or endogenous steroids (glucocorticoids). Glucocorticoids (also known as anti-inflammatory corticosteroids, corticosteroids, or simply as "steroids" in the ophthalmic literature) have been known since the early 1950's as effective therapeutic agents for reducing ocular inflammation. The introduction of anti-inflammatory steroid therapy, using a variety of local and systemic routes of delivery, continues to provide a means to decrease the inflammation which otherwise would damage and impair the vision of the patient. Ophthalmic steroid therapy proved useful to a wide variety of inflammatory and irritating conditions in the eye where other therapies either did not work as well or were ineffective. Steroids were not useful for many other conditions, especially chronic ones in which inflammatory mechanisms did not play a clear pathogenic role (including cataract, most forms of glaucoma, and macular degeneration). As ophthalmic steroid therapy became more widespread, and more potent and stable steroids became available, it became clear that their use involved a number of potential side-effects, one of the first of which noticed was elevation of pressure within the eye (intraocular pressure [IOP]). Concern over this side-effect has become a limitation on the long-term ophthalmic use of both potent and less active steroids, especially because a number of cases were reported in which irreversible blindness has occurred due to unrecognized increased IOP. Web site: http://www.delphion.com/details?pn=US05474985__ •
Prevention and treatment of ocular neovascularization by treatment with angiostatic steroids Inventor(s): Clark; Abbot F. (Arlington, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 5,679,666 Date filed: November 21, 1994 Abstract: Methods and formulations for treating ocular neovascularization using angiostatic steroids are disclosed. Excerpt(s): This invention relates to the use of angiostatic steroids in preventing and treating ocular neovascularization. Steroids functioning to inhibit angiogenesis in the presence of heparin or specific heparin fragments are disclosed in Crum, et el., A New Class of Steroids Inhibits Angiogenesis In The Presence of Heparin or Heparin Fragment, Science, 230, pp. 375-378 (Dec. 20, 1985). The authors refer to such steroids as "angiostatic" steroids. Included in the new class of steroids found to be angiostatic are cortisol, cortexolone, and several dihydro and tetrahydro derivatives. In a follow up study directed to testing a hypothesis as to the mechanism by which the steroids inhibit angiogenesis, it was shown that heparin/angiostatic steroid compositions caused dissolution of the basement membrane scaffolding to which anchorage dependent
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endothelia are attached resulting in capillary involution; see, Ingber, et el. A Possible Mechanism for Inhibition of Angiogenesis by Angiostatic Steroids: Induction of Capillary Basement Membrane Dissolution, Endocrinology 119, pp. 768-775 (1986). A group of tetrahydrosteroids useful in inhibiting angiogenesis is disclosed in U.S. Pat. No. 4,975,537, issued to Aristoff, et el. The compounds are disclosed for use in treating head trauma, spinal trauma, septic or traumatic shock, stroke, and hemorrhage shock. In addition, the patent discusses the utility of these compounds in embryo implantation and in the treatment of cancer, arthritis, and arteriosclerosis. The compounds are not disclosed for ophthalmic use. Some of the tetrahydrosteroids disclosed in Aristoff, et al. are disclosed in U.S. Pat. No. 4,771,042 in combination with heparin or a heparin fragment for inhibiting angiogenesis in a warm blooded animal. The patent does not disclose the combination for ophthalmic use. Web site: http://www.delphion.com/details?pn=US05679666__ •
Process for 1.alpha.,3.beta.-dihydroxy-.DELTA.sup.5 -steroids Inventor(s): Furst; Andor (Basel, CH), Labler; Ludwig (Allschwil, CH), Meier; Werner (Bottmingen, CH) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,305,881 Date filed: November 13, 1979 Abstract: A process for the synthesis of 1.alpha.,3.beta.-dihydroxy-.DELTA.sup.5 steroids from steroids such as 1.alpha.,2.alpha.-epoxy-cholesta-4,6-dien-3-one, which is reacted with lithium in liquid ammonia in the absence of a proton donator and subsequently reduced by repeated alternative additions of a proton donator, said additions being followed in each case by an equivalent amount of lithium. The final product, a 1.alpha.,3.beta.-dihydorxy-.DELTA.sup.5 -steroid, is useful in the synthesis of derivatives of cholecalciferol. Excerpt(s): The steroid compounds to which this invention relates are intermediates useable in the synthesis of derivatives of cholecalciferol (Vitamin D.sub.3). In particularly the invention relates to the synthesis of intermediates useable for the synthesis of 1.alpha.-hydroxy or 1.alpha.,25-dihydroxy-cholecalciferol which has been shown to possess advantageous therapeutic properties [DeLuca, et.al., Physiological Reviews 53, 327(1973)]. U.S. Pat. No. 3,901,928 relates to the preparation of 1.alpha.,3.beta.-dihydroxy steroid-5-ene by reacting starting compounds such as 1.alpha.,2.alpha.-epoxy-steroid-4,6-dien-3-ones with an alkali metal/liquid ammonia in the presence of a proton source. In a third step the steroid of partial formula IV is reduced to give the steroid of partial formula I by repeated alternating addition of a proton donator, in each case followed by the amount of lithium substantially equivalent stoichiometrically to the amount of proton donator. 1.alpha.,2.alpha.-epoxy-25-(1ethoxyethoxy)-cholesta-4,6-dien-3-one. Web site: http://www.delphion.com/details?pn=US04305881__
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Process for 7-keto-.DELTA.sup.5 -steroids Inventor(s): Salmond; William G. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,006,172 Date filed: April 26, 1976 Abstract: Disclosed is an improved process for the oxidation of certain.DELTA.sup.5 steroids to the corresponding 7-keto-.DELTA.sup.5 -steroids by use of a chromium trioxide-pyrazole oxidant (oxidizing agent). Excerpt(s): The transformation of a.DELTA.sup.5 -steroid to a 7-keto-.DELTA.sup.5 steroid has long been known in the steroid literature as a desirable means for the preparation of intermediates which are then converted to many other pharmaceutically useful steroids. For example, cholesteryl acetate is transformed to 7-ketocholesteryl acetate. See Dauben, et al. J. Org. Chem. 34, 3587 (1969). The intermediate 7ketocholesteryl is then converted to cholesta-5,7-diene-3-ol 3-acetate (provitamin D.sub.3) see Dauben, et al. J. Org. Chem. 36, 3277 (1971). Provitamin D.sub.3 is then converted to Vitamin D.sub.3 by methods well known to those skilled in the art. Similarly 17.alpha.-methyl-androsta-5-ene-7-one-3.beta.,17.beta.-diol diacetate is formed by the oxidation of 17.alpha.-methyl-androsta-5-ene-3.beta.,17.beta.-diol diacetate. 17.alpha.-Methyl-androsta-5-ene-7-one-3.beta.,17.beta.-diol diacetate is then converted to calusterone (7.beta.,17.alpha.-dimethyltestosterone) a useful anabolic agent and gonadatropin inhibitor. See U.S. Pat. No. 3,654,320. The known methods for oxidizing.DELTA.sup.5 -steroids to 7-keto-.DELTA.sup.5 -steroids include sodium chromate in conjunction with acetic anhydride and acetic acid but this demands long reaction time and undesirable by-products are formed. t-Butyl chromate has also been used but this is a hazardous reagent and is best avoided. Bispyridine chromium trioxide is known to achieve the oxidation cleanly, but again reaction times are long and large excesses of chromium reagent are required. In short the oxidation methods available are either hazardous, time consuming or inconvenient in their use. Web site: http://www.delphion.com/details?pn=US04006172__
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Process for converting 1,2-saturated steroids to 1,2-dehydro steroids Inventor(s): Evans; Timothy W. (Park Township, Three Rivers County, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,684,610 Date filed: April 17, 1985 Abstract: Disclosed and claimed is an improved microbial bioconversion to produce 1,2dehydro steroids from their corresponding 1,2-saturated derivatives by use of a waterimmiscible solvent comprising an aromatic hydrocarbon in the reaction procedure. Excerpt(s): The first therapeutic use of corticosteroids was demonstrated in the 1950's with the introduction of cortisone acetate treatment for rheumatoid arthritis. Further studies demonstrated that the insertion of unsaturation into the 1,2 position of hydrocortisone and cortisone caused the resultant steroids, prednisolone and prednisone, to have enhanced potency and to cause less drug-induced salt retention. Subsequently, most other steroids used for the treatment of corticoid-responsive diseases have been synthesized so that they contain a double bond in the 1,2 position of
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the steroid molecule. In 1977, two U.S. patents were issued which represent new approaches to the synthesis of corticosteroids from sterol precursors. U.S. Pat. No. 4,035,236 covers a process for preparing 9.alpha.-hydroxyandrostenedione via fermentation of sitosterol, stigmasterol, or cholesterol. U.S. Pat. No. 4,041,055 discloses a general process for the synthesis of medically useful corticosteroids from this androstene. Intermediates covered in this chemistry can possess a 3-keto.DELTA.sup.4,9(11) configuration. Description of 1-dehydrogenation of steroids in fermentation beers by Arthrobacter (Corynebacterium) simplex. Description of 1dehydrogenation of steroids by use of A. simplex cells pretreated with a lower alkanol or lower alkanone such as acetone before mixing with the substrate and a hydrogen carrier. Web site: http://www.delphion.com/details?pn=US04684610__ •
Process for preparing 16-methylene steroids Inventor(s): VanRheenen; Verlan H. (Portage, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,416,821 Date filed: February 17, 1982 Abstract: A process is disclosed for the production of 17-keto-16-methylene steroids (III) from the corresponding readily available 17-keto steroid (I) via a novel intermediate (II). Excerpt(s): 16-Methylene steroids are well known chemically in the estrone (aromatic A ring) series, see U.S. Pat. No. 3,257,429; in the corticoid series, see U.S. Pat. Nos. 3,157,679, 3,878,228, 3,354,184, 3,493,558 and 3,376,294; in the progesterone series, see U.S. Pat. Nos. 3,168,537, 3,157,679, 3,284,476 and 3,359,287; and in the androstane series, see U.S. Pat. Nos. 3,641,069 and 3,300,521. Pharmacologically, the 16-methylene steroids are known to be useful as anti-inflammatory agents, see U.S. Pat. Nos. 3,641,069, 3,878,228 and 3,359,287; as progestational agents, see U.S. Pat. Nos. 3,157,679, 3,168,537, 3,284,476, 3,359,287 and 3,493,558; as estrogen hormonal agents, see U.S. Pat. Nos. 3,257,429 and 3,284,476; and as intermediates, see U.S. Pat. Nos. 3,300,521 and 3,354,184. While there is more than one process to produce 16-methylene steroids, the most common process is the transformation of a 16-unsaturated-16-methyl steroid to the corresponding 16-methyl-16.alpha.,17.alpha.-epoxide followed by conversion to the corresponding 17.alpha.-hydroxy-16-methylene steroid, see U.S. Pat. Nos. 3,168,537, 3,354,184, 3,539,287, 3,493,558, 3,376,294 and 3,284,476. In addition, there is a process for the conversion of 17-keto steroids (I) to the corresponding 16-methylene steroid (III) by reacting the 17-keto steroid with formaldehyde (paraformaldehyde) and an amine followed by elimination of the amine, see U.S. Pat. Nos. 3,704,253 and 3,275,666. The process of the present invention first selectively activates the C.sub.16 position before reaction with formaldehyde and a base. Web site: http://www.delphion.com/details?pn=US04416821__
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Process for preparing androstane steroids Inventor(s): Imada; Yukio (Machida, JP), Osozawa; Tetsu (Machida, JP), Morimoto; Yuki (Yokohama, JP), Kinoshita; Masayuki (Ibaragi, JP) Assignee(s): Mitsubishi Chemical Industries Limited (Tokyo, JP) Patent Number: 4,397,946 Date filed: May 26, 1981 Abstract: Androstane steroids are produced by microbiological conversion of a sterol substrate with a microorganism belonging to the genus Mycobacterium wherein the medium used contains at least 0.1% by weight of egg yoke as a dry weight. Excerpt(s): This invention relates to a process for producing androstane steroids. More particularly it relates to an improvement in the culture medium used in the fermentative production of androstane steroids. It is well known in the art that an androstane steroid can be produced by microbiological conversion of a sterol with a microorganism belonging to the genus Mycobacterium (hereinafter abbreviated as "M."). However, this method involves some disadvantages in that the yield of the desired steroid is not yet satisfactory with the rate of production being low. It is also known that in the steroid fermentation wherein progesterone is hydroxylated at the 11.alpha.-position with the aid of Rhizopus nigricans one of fungi, the substrate (i.e., progesterone) can be fed at a higher concentration by adding it as a mixture with raw egg yolk in the course of incubation, as compared with the cases where progesterone is added as a solution in acetone without use of raw egg yolk (Japanese Patent Publication No. 9765/1957). Web site: http://www.delphion.com/details?pn=US04397946__
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Process for producing 6.alpha.-fluoro-.DELTA.sup.1,4 -3-keto steroids Inventor(s): Shephard; Kenneth P. (Portage, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,340,538 Date filed: July 21, 1980 Abstract: Two processes are disclosed (one-pot and two-pot) for the transformation of a 6.beta.-fluoro-.DELTA.sup.1,4 -3-keto steroid (IV) to a 6.alpha.-fluoro-.DELTA.sup.1,4 3-keto steroid (VI). These processes permit the introduction of a fluorine atom at the 6.alpha. position of a.DELTA.sup.1,4 -3-keto steroid where previously the.DELTA.sup.1 double bond could not be introduced until after the 6.alpha.-fluorine atom was present. The 6.alpha.-fluoro-.DELTA.sup.1,4 -3-keto steroids (VI) are intermediates useful in the production of pharmacologically active steroids. Excerpt(s): Diflorasone diacetate, fluocortolone, fluocinolone acetonide, fluocinonide, paramethasone and fluprednisolone are 6.alpha.-fluoro-.DELTA.sup.1,4 -3-keto steroids which are of pharmacological value primarily as topical anti-inflammatory agents. Present technology requires that the production of these 6.alpha.-fluoro-.DELTA.sup.1,4 -3-keto steroids necessitates the epimerization of the 6.beta.-fluoro group of a steroid prior to.DELTA.sup.1 -dehydrogenation. See, for example, U.S. Pat. Nos. 3,980,778, 3,014,938 and 3,126,375 and J. Am. Chem. Soc. 82, 4001 (1960). It would be highly desirable to be able to epimerize a fluorine atom at the 6.beta.-position in a.DELTA.sup.1,4 -3 keto steroid. However, prior to the present invention there was no known procedure for accomplishing this process.
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Web site: http://www.delphion.com/details?pn=US04340538__ •
Process for separating 3-hydroxy steroids or sterols from mixtures such as lipids Inventor(s): Crawford; Richard R. (Pittsford, NY), Blum; William P. (Rochester, NY), Naramore; David C. (Pittsford, NY) Assignee(s): Eastman Kodak Company (Rochester, NY) Patent Number: 4,425,275 Date filed: July 12, 1982 Abstract: A process for separating 3-hydroxy steroids from sterol concentrate mixtures by combining a solution of the sterol-containing mixture in a cosolvent of a dialkyl ketone and a low molecular weight alcohol with a slurry or solution of calcium bromide. The complexed sterols are isolated by filtration and the sterols can be subsequently liberated from the complex by treatment with an aqueous/alcohol and isolated by filtration and drying. The complexed sterols are of large particle size which allows rapid filtration. Excerpt(s): The present invention relates to a process for separating sterols from sterol concentrate mixtures. Various processes are known in the art for separating sterols such as 3-hydroxy steroids from mixtures of such sterols and other components such as lipids. One such mixture is phytosterols in soybean oil deodorizer distillate. The separation of the 3-hydroxy steroids from such mixtures is important because these 3hydroxy steroids are useful as raw materials for production of steroid drugs such as hydrocortisone. One such known process is described in German Pat. No. 827,199 wherein the mixture is dissolved, preferably in a hydrocarbon solvent, and is heated with a four- to sixteen-fold excess of anhydrous zinc chloride. After cooling of the solution, the precipitated ZnCl-sterol adduct can be separated out and the complex separated into the individual components. Another such known process as set forth in British Pat. No. 1,164,769 describes a method for the isolation of sterols from mixtures wherein the mixture is dissolved, preferably in a hydrocarbon solvent, the solution is mixed with an aqueous solution of a metal salt which is suitable for complex formation, the water is progressively removed by azeotropic distillation, and the precipitated adduct is isolated and the sterol recovered in a conventional manner after cooling of the mixture. Such known methods have the disadvantage that they are technically very costly on account of the high reaction temperature (customarily over 100.degree. C.) and that in the isolation of many 3-hydroxy steroids and 3-oxo steroids considerable loss of product is experienced, since these steroids can be destroyed under these conditions. In addition, these known methods often have the disadvantage that the recovery of the metal salt used for formation of the adduct, which is necessary in a method carried out on large scale simply with regard to environmental considerations, is often very costly. Web site: http://www.delphion.com/details?pn=US04425275__
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Process for synthesizing A-nor and A-nor-18-homo-steroids Inventor(s): Crabbe; Pierre (Columbia, MO) Assignee(s): World Health Organization (Geneva, CH) Patent Number: 4,309,565 Date filed: April 15, 1980
Patents 381
Abstract: The present invention is directed to a process for synthesizing A-nor and Anor-18-homo-steroids. The invention is concerned with providing a total synthesis for the compounds called Dinordin and 18-homo-Dinordin. The preparation of other compounds will also be evident. Excerpt(s): The present invention is related to a process for synthesizing A-nor and Anor-18-homo-steroids. The invention is particularly concerned with providing a total synthesis for the compounds called Dinordrin and 18-homo-Dinordrin although the preparation of other related compounds will also be evident. These compounds have been reported to have unusual fertility inhibitor properties. For example, Dinordrin appears to be about ten times more potent than Anordrin (the dipropionate of 2.alpha., 17.alpha.-diethynyl-A-nor-5.alpha.-androstane-2.beta., 17.beta.-diol). See P. Crabbe, H. Fillion, Y. Letourneux, E. Diczfalusy, A. R. Aedo, J. W. Goldzieher, A. A. Shaikh, and V. D. Castracane, Steroids, 1979, 33, 85; P. Crabbe, D. Andre and H. Fillion, Tetrahedron Letters, 1979, 893. Prior procedures for preparing 1a and 1b and generally similar products, including Anordrin, are inconveniently lengthy and low yielding and there is a real need for a versatile, short, total synthetic scheme for preparing these products. The principle object of the present invention is to provide such a process. A more specific object is to provide a relatively short synthetic route which affords the desired products in a convenient manner and in good yield. Other objects will also be hereinafter evident. Web site: http://www.delphion.com/details?pn=US04309565__ •
Process for the manufacture intermediates useful therein
of
3-keto-6-azido-4,6-bis-dehydro-steroids
and
Inventor(s): Green; Michael J. (East Brunswick, NJ), Bisarya; Satish C. (Moradabad, IN) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 3,931,167 Date filed: June 10, 1974 Abstract: Pharmacologically valuable 3-keto-6-azido-4,6-bis-dehydro-steroids are prepared by treating a 3-keto-6.beta.,7-diacyloxy-4-dehydro-steroid, preferably a 3-keto6.beta.,7.beta.-diacyloxy-4-dehydrosteroid, wherein said acyloxy group is a good leaving group (e.g. hydrocarbonsulfonyloxy), with an azide salt in a nonreactive organic solvent. Novel intermediates for this process, i.e. novel 3-keto-6.beta.,7.beta.-dihydroxy4-dehydro-steroids and 6.beta.,7.beta.-dihydrocarbonsulfonyloxy-esters thereof, are conveniently prepared by treating a 3-keto-4,6-bis-dehydro-steroid with osmium tetroxide followed by reductive cleavage of the 6.beta.,7.beta.-osmate ester thereby formed, isolating and thence esterifying the resulting 3-keto-6.beta.,7.beta.-dihydroxy-4dehydro-steroid with a hydrocarbonsulfonyl halide in a tertiary amine. Excerpt(s): This invention relates to a novel process for the preparation of pharmacologically active 3-keto-6-azido-4,6-bis-dehydro-steroids, and to novel 3-keto6.beta.,7.beta.-dihydrocarbonsulfonyloxy-4-dehydro-steroids useful as intermediates therein. 3-keto-6-azido-4,6-bis-dehydro-steroids are known compounds having pharmacological activity and/or being useful as intermediates in preparing other valuable steroidal derivatives. Prior art methods for preparing these compounds are described in U.S. Pat. Nos. 3,665,017 and 3,707,484 and comprise treating a 3-keto6.beta.-azido-7.alpha.-acyloxy-4-dehydro-steroid which is saturated at C-1 and C-2 with a tetraalkylammonium halide in an aprotic solvent or with a hydrochloric acid-acetic
382 Steroids
acid mixture in an inert solvent. By these prior art methods, a 6-azido-1,4,6-tri-dehydrosteroid cannot be obtained directly, it being necessary to first prepare a 3-keto-6-azido4,6-bis-dehydro-steroid and then introduce the 1-dehydro bond by treatment with 2,3dichloro-5,6-dicyanobenzoquinone (DDQ) in the presence of a strong acid and water. Additionally, when preparing a 3-keto-6-azido-4,6-dehydro-steroid having a 9.alpha.halogeno-11.beta.-hydroxy system by the prior art methods, in order to minimize competing side reactions, it is necessary to esterify the hydroxyl group at C-11 prior to preparing the 6.beta.-oxido-7.alpha.-acyloxy intermediate, thus necessitating a second additional step of removing the ester at C-11 after the desired 6-azido-4,6-bis-dehydrosteroid has been prepared. Web site: http://www.delphion.com/details?pn=US03931167__ •
Process for the manufacture of 6.beta.,7-methylene-3-oxo-4-ene steroids Inventor(s): Wieland; Peter (Oberwil, CH) Assignee(s): Ciba-Geigy Corporation (Ardsley, NY) Patent Number: 4,119,627 Date filed: March 29, 1977 Abstract: The invention provides a novel general process for the manufacture of 6.beta.,7-methylene-3-oxo-4-ene-steroids by successively (a) reacting a 3.xi.,5.beta.dihydroxy-6-ene-steroid which is optionally etherified or esterified in the 3-position with a zinc/copper-methylene iodide reagent to introduce the 6.beta.,7-methylene bridge, (b) liberating an etherified or esterified 3-hydroxyl group if such a group is present, (c) treating the resultant 6.beta.,7-methylene-3.xi.,5.beta.-dihydroxy-steroid with an oxidizing agent to dehydrogenate the 3-hydroxyl group to the oxo group, and (d) dehydrating the 6.beta.,7-methylene-5.beta.-hydroxy-3-oxo-steroid to form the 4,5double bond. The starting materials, which form a novel class of compounds, can be obtained by a novel process by converting a 5.beta.,6-oxido-3.xi.-hydroxy-steroid with a selenol, for example phenylselenol, to a 6.alpha.-alkyl- or arylseleno-3.xi.,5.beta.dihydroxy-steroid, oxidizing this compound with a peroxidic reagent, for example hydrogen peroxide, in a weakly acid medium to give the corresponding 6-selenonyl compound, and converting this compound, preferably by treatment with a base, preferably with 1,5-diazabicyclo[4,3,0]non-5-ene, to give the 3.xi.,5.beta.-dihydroxy-6ene-steroid. During the course of these reactions, the 3-hydroxyl group is preferably temporarily protected by esterification or etherification. Excerpt(s): Wherever it occurs in the context of an organic radical, the term "lower" denotes a corresponding radical with at most 7, and preferably with at most 4, carbon atoms. The symbol n preferably denotes the number 1. A lower alkyl radical is, for example, a n-propyl, i-propyl, n-butyl, i-butyl, sec.-butyl or tert.-butyl radical or a branched or, preferably, straight-chain pentyl, hexyl or heptyl radical, but above all an ethyl or methyl radical. A lower aliphatic hydrocarbon radical is to be understood meaning a lower alkyl radical, for example one of those already mentioned, which optionally also contains one or two multiple bonds, that is to say double bonds or triple bonds, such as, for example, a lower alkenyl, lower alkynyl and allenyl radical, for example a vinyl, allyl, methallyl, propargyl, hexadiynyl and, above all, ethynyl radical. Web site: http://www.delphion.com/details?pn=US04119627__
Patents 383
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Process for the manufacture of hydroxylated steroids Inventor(s): Fujiwara; Mitsuhiko (Kamakura, JP), Fujiwara; Akiko (Kamakura, JP), Miyamoto; Chikara (Yokohama, JP) Assignee(s): Hoffmann-La Roche, Inc. (Nutley, NJ) Patent Number: 4,336,332 Date filed: February 4, 1980 Abstract: The invention relates to a process for producing 7.sub.alpha. -hydroxylated steroids by fermenting or reacting a steroid to be hydroxylated with microorganisms of the genus Botryodiplodia or enzyme extracts thereof until hydroxylation occurs. The invention process produces steroid compounds which are pharmacologically valuable substances. Excerpt(s): The microbiological 7.alpha.-hydroxylation of steroids by means, for example, of Mucor griseocyanus is known and described in Canadian Journal of Microbiology, Vol. 13, pages 1271-1281 (1967). It has now surprisingly been found that a 7.alpha.-hydroxylation of steroids can be carried out with microorganisms of the genus Botryodiplodia, which are entirely different from Mucor griseocyanus. The invention relates in its preferred embodiment to a process for the manufacture of 7.alpha.hydroxylated steroids by fermentation of 7-unsubstituted steroids of the pregnane or androstane series with microorganisms of the genus Botryodiplodia or by reaction with enzyme extracts thereof. The invention process produces steroid compounds which are intermediates for the manufacture of pharmacologically valuable substances and which themselves exhibit pharmacological (e.g. hormonal) activity. The present invention relates to a process for producing hydroxylated steroids comprising fermenting a steroid to be hydroxylated with microorganisms of the genus Botryodiplodia in a culture solution or medium until the steroid to be hydroxylated is hydroxylated. The invention process also includes a process for producing hydroxylated steroids comprising reacting the steroid to be hydroxylated with a hydroxylating enzyme extract obtained from the microorganisms of genus Botryodiplodia in a reaction mixture until the steroid to be hydroxylated is hydroxylated. Web site: http://www.delphion.com/details?pn=US04336332__
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Process for the microbial transformation of steroids Inventor(s): Knight; John C. (Kalamazoo, MI), Wovcha; Merle G. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,304,860 Date filed: February 13, 1978 Abstract: Novel compounds prepared by microbial transformation using novel mutants to selectively degrade steroids with or without 17-alkyl side chains of from 2 to 10 carbon atoms, inclusive. These compounds can be used as intermediates to make useful steroids. Excerpt(s): The transformation of steroids by microorganisms has been widely studied and documented. Apparently, the earliest such work was by Mamoli and Vercellone in 1937, Ber. 70, 470 and Ber. 70, 2079. They disclosed the reduction of 17-ketosteroids to 17.beta.-hydroxysteroids by fermenting yeast. More recently, Peterson and Murray disclosed the 11.alpha.-hydroxylation of progesterone with the fungus Rhizopus
384 Steroids
nigricans; see, U.S. Pat. No. 2,602,769 (1952). Also recently, Kraychy et al. in U.S. Pat. No. 3,684,657 (1972) discloses the selective microbiological degradation of steroidal 17-alkyls by fermenting a steroid containing at least 8 carbons in the 17-alkyl side chain with Mycobacterium sp. NRRL B-3683 to prepare androst-4-ene-3,17-dione, androst-1,4diene-3,17-dione, and 20.alpha.-hydroxymethyl-pregna-1,4-dien-3-one. Even more recently, Marsheck et al. in U.S. Pat. No. 3,759,791 (1973) disclose the selective microbiological preparation of androst-4-ene-3,17-dione by fermenting a steroid of the cholestane or stigmastane series containing at least 8 carbons in the 17-alkyl side chain with Mycobacterium sp. NRRL B-3805. Compound III of the subject invention has been disclosed by Wang and Sih in 1963 (Biochem. 2: 1238-1243) as an intermediate in the degradation of androst-4-ene-17.beta.ol-3-one by Nocardia restrictus. The open ring form of compound 1, 7.alpha.-methyl-perhydroindanedione-(1,5)-[.beta.-propyl alcohol(4)], has been disclosed by Schubert et al. in 1964 (Steroids 4: 581-586) as an intermediate in the degradation of progesterone by Mycobacterium smegmatis. These mutants can be obtained from sterol-degrading microorganisms of the following genera by using the mutation procedures disclosed herein or other mutation procedures: Arthrobacter, Bacillus, Brevibacterium, Corynebacterium, Mycobacterium, Nocardia, Protaminobacter, Serratia, and Streptomyces. A preferred genus is Mycobacterium. Exemplary species of this genus are M. phlei, M. smegmatis, M. rhodochrous, M. mucosum, M. fortuitum, and M. butyricum. Specifically exemplifed herein is a novel mutant microorganism, Mycobacterium fortuitum, NRRL B-8128, which is used to selectively degrade steroids with or without 17-alkyl side chain containing from 2 to 10 carbon atoms, inclusive, to the compounds I, II, III and IV. Examples of suitable steroids are sitosterols, cholesterol, stigmasterol, campesterol, and like steroids with 17-alkyl side chains of from 2 to 10 carbon atoms, inclusive, and androst-4-ene-3,17-dione, androsta1,4-diene-3,17-dione, dehydroepiandrosterone, and testosterone. These steroids substrates can be in either the pure or crude form. Web site: http://www.delphion.com/details?pn=US04304860__ •
Process for the preparation of 19-hydroxy steroids of the androstane and pregnane series Inventor(s): Petzoldt; Karl (Berlin, DE) Assignee(s): Schering, A.G. (Berlin, DE) Patent Number: 4,284,720 Date filed: January 14, 1980 Abstract: 10-Methyl steroids of the androstane or pregnane series are converted to the corresponding 19-hydroxy steroid by fermentation with a fungal culture of the genus Nigrospora. Excerpt(s): The invention concerns a process for preparing 19-hydroxy-steroids of the androstane and pregnane series. 19-Hydroxy steroids are, as is known, important intermediates for the partial synthesis of pharmacologically active 19-nor steroids. The chemical synthesis of these compounds from the corresponding 10-methyl steroids comprises many stages and is very expensive (J. Amer. Chem. Soc. 84:3204 et seq. [1962] and J. Amer. Chem. Soc. 83:4076 et seq. [1961]). Investigations have also been conducted to hydroxylate 10-methyl steroids in the 19-position by means of microorganism cultures (Bull. Agr. Chem. Japan 22:212 [1958]). However, the previously known methods yield only such low quantities of 19-hydroxy steroids that they are useless from a technical viewpoint. In contrast thereto, it is possible with the aid of the process
Patents 385
of this invention to convert 10-methyl steroids into the corresponding 19-hydroxy steroids in high yields. Web site: http://www.delphion.com/details?pn=US04284720__ •
Process for the preparation of 21-hydroxy-20-keto-.DELTA.sup.16 -steroids and new intermediate compounds formed in this process Inventor(s): van Leusen; Albert M. (Groningen, NL), van Leusen; Adriaan M. (Winsum, NL) Assignee(s): Gist-Brocades N.V. (Delft, NL) Patent Number: 4,548,749 Date filed: April 27, 1984 Abstract: A novel process for the preparation of 21-hydroxy-20-keto-.DELTA.sup.16 steroids comprising reacting a 17-(isocyanosulfonylmethylene)-steroid with an aldehyde and an alcohol to form a 17-(2-alkoxy-3-oxazolin-4-yl)-.DELTA.sup.16 -steroid and subjecting the latter to hydrolysis to obtain the corresponding 21-hydroxy-20-keto.DELTA.sup.16 -steroid which are useful to prepare corticoid steroids and novel intermediates. Excerpt(s): Steroids are used on a large scale as the active ingredients of many types of pharmaceutical compositions and depending on the substituent pattern of the carbonskeleton, the steroids can be divided into a number of main classes. An important main class of steroids is formed by the cortico-steroids whose natural representatives are usually produced by the adrenal gland. Corticosteroids are characterized by the presence of a 3-keto group, a.DELTA.sup.4 -double bond, an 11.beta.-hydroxy group, a 17.alpha.-hydroxy group and a 17.beta.-hydroxy-acetyl side chain. For a long time, corticosteroids were made by chemical degradation of gall acids such as cholic acid, desoxycholic acid and glycocholic acid. Afterwards, hecogenin which could be isolated from plants, particularly from numerous Agave species, became an important raw material too. Since the possibility of the introduction of an 11-hydroxy group by microbiological methods diosgenin which could be isolated from numerous Dioscoreacaea species and stigmasterol, usually isolated from the phytosterol mixtures from soya or calabar beans, have become the most important raw material for the preparation of corticosteroids. Much attention has been given to new, cheaper raw materials for the synthesis of pharmaceutically active steroids. Therefore, the degradation of the abundant soya bean derived sterols, sitosterol and campesterol by microbiological methods into 17-oxo-steroids was extensively investigated and as a result thereof, 17-oxo-steroids are readily available now at low prices which makes these compounds, together with the possibility of the introduction of an 11-hydroxy group by microbiological methods, ideal starting materials for corticosteroid synthesis. Web site: http://www.delphion.com/details?pn=US04548749__
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Process for the preparation of 7.alpha.-halogeno-3-oxo-4-dehydro steroids and novel 7.alpha.-halogeno derivatives produced thereby Inventor(s): Green; Michael J. (Kendall Park, NJ), Shue; Ho-Jane (Belleville, NJ), Shapiro; Elliot L. (Cedar Grove, NJ), Gentles; Margaret A. (Bloomfield, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 4,076,708 Date filed: December 22, 1976 Abstract: 3-Oxo-6-unsubstituted-7.alpha.-halogeno-4-dehydro steroids, wherein said halogen is chlorine, bromine or iodine, are prepared by reaction of a 3-oxo-6,7-diunsubstituted-4,6-bis-dehydro steroid with at least an equimolar quantity of the corresponding hydrogen halide in a non-reactive organic solvent at temperatures no higher than about 30.degree. C, and then are isolated by removal of said solvent and any excess acid at temperatures no higher than about 25.degree. C without subjecting said 3oxo-6-unsubstituted-7.alpha.-halogeno-4-dehydro steroid to a basic medium.A preferred species of this process is that wherein the starting steroid is a 3,20-dioxo-9unsubstituted-11-oxygenated-1,4,6-pregnatriene-17,21-diol or ester thereof, preferably a 17,21-di-lower alkanoate or a 17-benzoate 21-lower alkanoate ester thereof, whereby is prepared in good yields a 3,20-dioxo-7.alpha.-halogeno-1,4-pregnadiene-17.alpha.,21diol or ester thereof, useful as topical anti-inflammatory agents.Also described are novel 3,20-dioxo-7.alpha.-halogeno-4-pregnene-17.alpha.,21-diols and esters thereof having anti-inflammatory activity as well as 3-oxo-7.alpha.-halogeno-17.alpha.-4-pregnene21,17.beta.-carbolactone aldosterone antagonists. Excerpt(s): This invention relates to a novel process and to novel compositions-of-matter produced thereby. More specifically, this invention relates to a process for preparing 3oxo-6-unsubstituted-7.alpha.-halogeno-4-dehydro steroids and to novel steroidal derivatives produced thereby. In particular, this invention relates to a process for preparing 3-oxo-6-unsubstituted-7.alpha.-halogeno-4-dehydro steroids and to novel 3,20-dioxo-6-unsubstituted-7.alpha.-halogeno-4-pregnene anti-inflammatory agents and 3-oxo-6-unsubstituted-7.alpha.-halogeno-17.alpha.-4-pregnene-21,17.beta.-c arbolactone aldosterone antagonists produced thereby. Web site: http://www.delphion.com/details?pn=US04076708__
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Process for the preparation of 7.alpha.-hydroxylated steroids Inventor(s): Fujiwara; Mitsuhiko (Kamakura, JP), Fujiwara; Akiko (Kamakura, JP), Miyamoto; Chikara (Yokohama, JP) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,220,716 Date filed: September 5, 1978 Abstract: A fermentation process for the preparation of 7.alpha.-hydroxylated steroids utilizing strains of the genus Mucor is disclosed. The 7.alpha.-hydroxylated steroids are useful intermediates for the synthesis of chenodeoxycholic acid as well as steroidal hormones. Excerpt(s): The present invention relates to a process for the preparation of 7.alpha.hydroxylated steroids by fermenting 7-unsubstituted steroids of the pregnene or androstene series with microorganisms of the genus Mucor. The microbiological
Patents 387
preparation of 7.alpha.-hydroxylated steroids by means of microorganisms of the genera Cephalosporium, Helminthosporium, Curvularia, Rhizopus, Aspergillus, Diplodia and Cunninghamella has been described. However, the selective introduction of a hydroxy group in the 7.alpha.-position of steroids of the following formula I by means of microorganisms of the genus Mucor has not been described. In accordance with the invention there can be used all strains of the genus Mucor which are capable of 7.alpha.hydroxylating a 7-unsubstituted steroid of the formula I. Preferred strains are Mucor spinescens IAM-6071 (FERM P-No. 4141), Mucor circinelloides ETH-2605 (FERM P-No. 4142), Mucor hiemalis IFO-8448 (FERM P-No. 4143), and IFO-8449 (FERM P-No. 4144), Mucor plumbeus CBS 295.63, Mucor hiemalis FERM P-No. 3800 and variants thereof. Web site: http://www.delphion.com/details?pn=US04220716__ •
Process for the preparation of steroids Inventor(s): Torossian; Dieran R. (Bourg-La-Reine, FR), Aubard; Gilbert G. (Palaiseau, FR) Assignee(s): SIPSY (Avrille, FR) Patent Number: 4,269,778 Date filed: November 20, 1979 Abstract: Process for the preparation of steroids.The steroid 21-thioesters are prepared by preparing the corresponding sulphonates in acetonic suspension and by reacting this suspension directly with a thiocarboxylate.Preparation of synthesis intermediates. Excerpt(s): The present invention is concerned with steroids and, more especially with industrial processes for the preparation of intermediate steroids useful in the preparation of pharmacologically active compounds. The yields are often mediocre. The periods of synthesis comprising the times of reaction and of isolation of the intermediate sulphonate and of the thioester produced are at least 30 hours. The invention overcomes these disadvantages by enabling yields above 80% and currently reaching 90% to be obtained in total periods of synthesis of the order sometimes of 5 hours and of 3 to 4 hours only. Web site: http://www.delphion.com/details?pn=US04269778__
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Processes for preparation of 9,11-epoxy steroids and intermediates useful therein Inventor(s): Ng; John S. (Chicago, IL), Wang; Ping T. (St. Louis, MO), Baez; Julio A. (Chesterfield, MO), Liu; Chin (St. Louis, MO), Anderson; Dennis K. (St. Louis, MO), Lawson; Jon P. (St. Louis, MO), Erb; Bernhard (Gipf-Oberfrick, CH), Wieczorek; Joseph (Chicago, IL), Kunda; Sastry A. (St. Louis, MO), Letendre; Leo J. (St. Louis, MO), Pozzo; Mark J. (St. Louis, MO), Sing; Yuen-Lung L. (St. Louis, MO), Yonan; Edward E. (Carol Stream, IL) Assignee(s): G. D. Searle and Co. (Chicago, IL) Patent Number: 5,981,744 Date filed: December 11, 1996 Abstract: Multiple reaction schemes, process steps and intermediates are provided for the synthesis of epoxymexrenone, useful as a diuretic, and other 9,11-epoxy-steroids.
388 Steroids
Excerpt(s): This invention relates to the novel processes for the preparation of 9,11epoxy steroid compounds, especially those of the 20-spiroxane series and their analogs, novel intermediates useful in the preparation of steroid compounds, and processes for the preparation of such novel intermediates. Most particularly, the invention is directed to novel and advantageous methods for the preparation of methyl hydrogen 9,11.alpha.epoxy-17.alpha.-hydroxy-3-oxopregn-4-ene-7.alpha.,21-dicarboxy late,.gamma.-lactone (eplerenone; epoxymexrenone). R.sup.1 represents an.alpha.-oriented lower alkoxycarbonyl or hydroxycarbonyl radical. and salts of such compounds in which X represents oxo and Y.sup.2 represents hydroxy, that is to say of corresponding 17.beta.hydroxy-21-carboxylic acids. Web site: http://www.delphion.com/details?pn=US05981744__ •
Processing of steroids containing amino functionality Inventor(s): Krbechek; Leroy O. (Minneapolis, MN), Spitzner; Ernest B. (Minneapolis, MN), Clark; James P. (Forest Lake, MN) Assignee(s): Henkel Corporation (Minneapolis, MN) Patent Number: 4,252,732 Date filed: February 19, 1980 Abstract: The present invention describes the conversion of steroids having a 20-amino functionality to progesterone and other useful steroids. Excerpt(s): The present invention relates to obtaining steroid compounds from their amino precursors. This invention deals basically with the conversion of steroid compounds having an acid side chain to give useful intermediates and end compounds such as progesterone. For instance, in published European patent application No. 4-913 dated Oct. 31, 1979, it was revealed that through microbiological transformation that it was possible to obtain a substantial yield of steroids having a 20 carbonyl functionality. It has also been observed that through following the teachings of the European patent that it is also possible to obtain 3-oxo-pregna-1,4,17(20)-triene-20-carboxylic acid. Of course, depending upon the pH of the solution, it is possible to obtain the carbonyl compounds as either the acid or salt or mixtures thereof. Web site: http://www.delphion.com/details?pn=US04252732__
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Pro-drugs for the improved delivery of certain selected anti-inflammatory steroids Inventor(s): Bodor; Nicolae S. (Lawrence, KS), Sloan; Kenneth B. (Eudora, KS) Assignee(s): INTERx Research Corporation (Lawrence, KS) Patent Number: 4,069,322 Date filed: October 12, 1976 Abstract: Transient, pro-drug forms of conventional anti-inflammatory steroids are disclosed. Excerpt(s): The present invention is directed to certain selected transient pro-drug forms of conventional anti-inflammatory steroids (e.g., cortisone, hydrocortisone, prednisone, prednisolone, etc.) useful in alleviating inflammatory conditions in warm-blooded animals. For the purposes of this application, the term "pro-drug" denotes a derivative
Patents 389
of a known and proven prior art anti-inflammatory steroid compound (e.g., cortisone, hydrocortisone, prednisone, prednisolone, etc.), which derivative, when administered to a warm-blooded animal, "cleaves" in such a manner as to release the proven drug form at its target site or sites of activity. The term "transient" denotes enzymatic and/or chemical hydrolytic "cleavage" of the compounds of the instant invention in such a manner such that the proven drug form (the conventional antiinflammatory steroid, e.g., cortisone, hydrocortisone, prednisone, prednisolone, etc.) is released while the remaining "cleaved" moiety remains nontoxic and is metabolized in such a manner that nontoxic, metabolic products are produced. Web site: http://www.delphion.com/details?pn=US04069322__ •
Pyrazinylpiperazinyl steroids Inventor(s): McCall; John M. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 5,382,661 Date filed: December 1, 1992 Abstract: Disclosed are amino substituted steroids (XI) which contain a pyrazinylpiperazinyl group attached to the terminal carbon atom of the C.sub.17 -side chain which are useful as pharmaceutical agents for treating a number of conditions. Excerpt(s): The present invention relates to amino substituted steroids which are useful as pharmaceutical agents. Various amino (substituted) steroids are known with the amine substitution on either the steroidal ring system or on the side chain of the D-ring at C.sub.17. U.S. Pat. No. 4,456,602 discloses steroidal 21-esters in which there is an amino function in the non-steroidal portion of the ester. Web site: http://www.delphion.com/details?pn=US05382661__
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Retinoic acid esters of steroids of the pregnane series, their use in the treatment of acne and pharmaceutical formulations useful therefor Inventor(s): Casmer; Charles J. (Rahway, NJ), Draper; Richard W. (East Orange, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 3,984,544 Date filed: February 28, 1975 Abstract: Novel retinoic acid esters of anti-inflammatory steroids of the pregnane series are described and their use in the treatment and control of acne vulgaris via the topical or intralesional route. A preferred mode of the invention comprises treating acne by applying topically to the affected area hydrocortisone 21-all-trans-retinoate in concentrations of from about 0.05 to about 0.15 percent. Pharmaceutical formulations and methods for the manufacture of the novel steroidal retinoates are also described. Excerpt(s): This invention relates to novel compositions-of-matter, methods for their manufacture, pharmaceutical formulations thereof and the method of using said formulations in the treatment and control of acne vulgaris. More specifically, this invention relates to novel retinoic acid esters of anti-inflammatory steroids of the pregnane series, pharmaceutical formulations thereof, and their use in the treatment and
390 Steroids
control of acne vulgaris. In particular, this invention relates to 21-retinoates, 17.alpha.retinoates, 16.alpha.-retinoates, 16.alpha.,21-diretinoates and 17.alpha.,21- diretinoates of 3,20-diketo-4-pregnenes and certain derivatives thereof having anti-inflammatory activity and having hydroxyl groups or hydrolyzable derivatives thereof on at least one of positions 17.alpha. and 21, to pharmaceutical formulations thereof, and their use in the treatment and control of acne vulgaris via the topical or intralesional route. Web site: http://www.delphion.com/details?pn=US03984544__ •
Selenium-75 steroids Inventor(s): Chambers; Virginia Edith May (Amersham, EN), Riley; Anthony Leonard Mark (Amersham, EN) Assignee(s): The Radiochemical Centre Ltd. (Amersham, EN) Patent Number: 3,952,030 Date filed: December 20, 1973 Abstract: Novel dimeric and monomeric selenium-75 derivatives of steroids are made by reacting a keto steroid with selenium-75 dioxide or selenious acid-Se75. The resulting diselenide dimers can be converted into monomeric compounds by the use of a cleaving reagent followed by an alkylating agent. The compounds are useful in saturation analyses such as radioimmunoassays. Excerpt(s): This invention relates in broad terms to selenium-75 derivatives of steroids, and particularly to two groups of novel selenium-75 derivatives of steroids; to the preparation of such novel derivatives; and to the use of both groups of compounds for saturation analysis. Derivatives for use in such analyses contain the.gamma.-emitting Se75 isotope. The preparation of steroids containing Se75 has not previously been described in the literature, neither has the idea of using Se75 labelled compounds for saturation analysis. A. EACH COMPOUND IS OBTAINABLE BY REACTING A 3KETO, OR A 6-KETO, OR A 7-KETO, OR A 17-KETO STEROID, PREFERABLY A.DELTA.sup.4,3-KETO STEROID, WITH SELENIUM-75 DIOXIDE OR SELENIOUS ACID-Se75. The reaction is preferably effected in an organic solvent for the steroid reactant which is unattacked by the selenium-75 reactant under the reaction conditions employed, and in which the basic steroid skeleton is stable. Suitable organic solvents include ethers, e.g. dioxan, organic acids, e.g. acetic acid, and benzene although it is likely that a wide range of solvents may be used. The reaction is generally carried out at an elevated temperature, e.g. from 80.degree.C to 140.degree.C, conveniently the reflux temperature of the organic solvent. Web site: http://www.delphion.com/details?pn=US03952030__
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Selenyl and telluryl derivatives of steroids Inventor(s): van der Veek; Augustinus Petrus Maria (Voorschoten, NL) Assignee(s): Philips-Duphar B.V. (Amsterdam, NL) Patent Number: 4,041,145 Date filed: November 28, 1975 Abstract: Selenyl- and telluryl derivatives of steroids are prepared having in general the formula of 19-methylselenyl or 19-methyltelluryl derivatives respectively of cholesterol
Patents 391
and related 3-oxy 5-.DELTA.-steroids, such as sitosterol and campesterol.More specifically these substances are prepared with radioactively labelled Se and Te atoms by first preparing compounds of the type of alkyl lithium selenides and tellurides respectively and related compounds and these are reacted with steroid compounds of the type stated having a smoothly transferable substituent in the 19 position.These labelled compounds are suitable for preparing diagnostic compositions for examination into internal organs such as the adrenal glands, applying scintigraph detection methods. They also can be applied for radio-immunologic determinations and other diagnostic determination methods. Excerpt(s): The invention relates to novel selenyl- and telluryl derivatives of steroids and to methods for the preparation of these compounds, as well as to the application of such compounds, labelled with radioactive selenium and tellurium isotopes, in diagnostic compositions in particular to be used with a method for diagnostic investigation into abnormalities of internal organs, viz. of the adrenal gland and with a radio-immunologic determination of the steroid-level in the blood or the urine. For the diagnostic investigation into abnormalities of internal organs, viz. the adrenal gland, according to the so-called "scintigraphic" methods, use has been made already of 19iodocholesterol labelled with iodine-isotopes.sup.125 I and.sup.131 I that after intravenous administration is found to accumulate itself sufficiently in the adrenal gland so as to be able to make a "scintigram" of it (See the publications by W. H. Beierwaltes, R. E. Counsel et al in J. Nucl. Med. 12, No. 4 (1971), 176, J. Am. Med. Assoc. 216, No. 2 (1971), 275, J. Clin. Endocrin. and Metab. 33 (1971), 713 and J. Nucl. Med. 14, No. 11 (1973), 777). A drawback of working with this radio-actively labelled 19-iodocholesterol is for instance the high irradiation load, viz. the thyroid gland being overloaded (see J. Nucl. Med. 14, No. 9 (1973), 713) and the poor stability of the compound, both in vivo and in vitro (see J. Nucl. Med. 15, No. 1 (1974), 38). Web site: http://www.delphion.com/details?pn=US04041145__ •
Skin permeation enhancer composition for use with sex steroids Inventor(s): Xia; Jun (Edison, NJ), Jona; Janan (Sunnyvale, CA), Chiang; Chia-Ming (Foster City, CA) Assignee(s): Cygnus, Inc. (Redwood City, CA) Patent Number: 5,693,335 Date filed: June 7, 1995 Abstract: A combination permeation enhancer for increasing the permeability of skin to sex steroids such as estrogens and progestogens comprising a polyhydric thioalcohol of 2 to 6 carbon atoms having at least one mercapto group and at least one hydroxy group and an aliphatic carboxylic acid of 8 to 24 carbon atoms or an ester thereof. Excerpt(s): The invention is in the field of transdermal drug delivery. More particularly, it concerns a skin permeation enhancer composition for increasing the permeability of skin to sex steroids. Transdermal patches for administering drugs, including steroids, are well known. Transdermal patches include a component, typically called the "reservoir," that holds the bulk of the drug to be administered. One type of patch uses a solid matrix composed of a mixture of a pressure sensitive adhesive and the drug as the reservoir. The matrix also serves as the means for attaching the patch to the skin. Such patches are often referred to as "matrix" or "monolith" type patches. Some drugs permeate unassisted through skin at rates that make it feasible to administer therapeutic
392 Steroids
amounts of the drug via a reasonably sized patch. For drugs that do not permeate through skin at such rates, it may be possible to increase the permeability of the skin to the drug with a permeation enhancer. For instance, most steroids require the use of a permeation enhancer to make transdermal administration feasible. Web site: http://www.delphion.com/details?pn=US05693335__ •
Steroids and process for preparing the same Inventor(s): Riva; Mario (Milan, IT), Toscano; Luciano (Milan, IT) Assignee(s): Pierrel S.p.A. (Milan, IT) Patent Number: 4,272,446 Date filed: January 12, 1979 Abstract: Novel steroids are described together with processes of making them and pharmaceutical compositions containing them. The steroids have pharmaceutical activity, especially antiinflammatory activity. They are all 2-Bromo-6.beta.-fluoropregna-1,4-diene-3,20-diones. Excerpt(s): The present invention relates to a new class of steroids having good antiinflammatory activity, to processes of making them and to pharmaceutical compositions containing them. Many steroids having anti-inflammatory activity upon topical and/or systemic administration are known and some of them have quite satisfactory antiinflammatory activity. Unfortunately they all tend to give undesired side effects. For instance they may disturb the mineral balance in the subject to which they are administered, for example they may reduce the potassium and/or sodium balance and they may affect adversely the adrenals function. Accordingly their application has to be conducted with caution. Web site: http://www.delphion.com/details?pn=US04272446__
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Steroids and process for their manufacture Inventor(s): Alig; Leo (Kaiseraugst, CH), Furst; Andor (Basel, CH), Muller; Marcel (Frenkendorf, CH), Kerb; Ulrich (Berlin, DE), Wiechert; Rudolf (Berlin, DE) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,252,729 Date filed: May 7, 1979 Abstract: The present disclosure is concerned with 9.alpha.-chloro-17-(miodobenzyloxy) steroids and a process for their manufacture. The subject compounds are useful as intermediates in the synthesis of pharmacologically-active substances and have themselves been found to exhibit pharmacological activity. Excerpt(s): Breslow et al., e.g., J. Amer. Chem. Soc. 96 (1974) 1973, ibid. 96 (1974) 6791, describe the chlorination of steroids which have been esterified at the 3.alpha.-position wherein the tertiary carbon atom in the 9-position is chlorinated with iodobenzene dichloride under the influence of light, and subsequently, hydrogen chloride is cleaved off with the formation of a 9,11-double bond. The disadvantage in the foregoing process is that it has utility in only those steroids which have no carboxy group or no unprotected carbonyl group in the 17.beta.-side chain. In accordance with the present
Patents 393
invention, it has been found that 9.alpha.-chloro-3-oxo-androst-4-ene-17.beta.-carboxylic acids can be selectively obtained in the unprotected form. It has further been found that the chlorination is effected selectively in the 9-position which is unexpected since, from the work of Halpern, e.g., Chem. & Ind. (1962), 1571, it was known that steroids with double bonds react with iodobenzene dichloride to give the corresponding.alpha.dichlorosteroids. The term "lower alkyl" used herein means, in particular, alkyl groups which are the characterizing groups of alkanols containing up to 4 carbon atoms; for example, methyl, ethyl, propyl, isopropyl, butyl and isobutyl. Web site: http://www.delphion.com/details?pn=US04252729__ •
Steroids as neurochemical initiators of change in human blood levels of LH Inventor(s): Jennings-White; Clive L. (Salt Lake City, UT), Berliner; David L. (Atherton, CA), Adams; Nathan W. (Salt Lake City, UT) Assignee(s): Pherin Corporation (Menlo Park, CA) Patent Number: 6,066,627 Date filed: March 29, 1996 Abstract: The invention relates to a method of altering the blood levels of LH or FSH in an individual. The method comprises nasally administering a steroid which is a human vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Excerpt(s): This invention relates generally to methods for altering the blood levels of luteinizing hormone or follicular stimulating hormone in humans. The present invention relates to certain steroids, and methods of using these steroids as human vomeropherins in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g., the reduction of anxiety. Ohloff, G. et al. (Helv. Chim. Acta (1983) 66:192-217), which is incorporated herein by reference, have shown that several steroids (androstenes) have an odor which varies with different isomeric, diastereomeric, and enantiomeric forms. Some members of this group have been reported to act as a pheromone in some mammalian species--for instance, 5.alpha.androst-16-en-3-one and 5.alpha.-androst-16-en-3.alpha.-ol in pigs (Melrose, D. R., et al., Br. vet. J. (1971) 127:497-502). These 16-androstenes produced by the boar induce mating behavior in estrus sows (Claus, et al., Experimentia (1979) 35:1674-1675). Some studies have noted that, in some species, various characteristics of certain 16-androstenes (including 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one), such as concentration, metabolism, and localization, are sexually dimorphic (Brooksbank et al., J. Endocr. (1972) 52: 239-251; Claus, et al., J. Endocr. (1976) 68:483-484; Kwan, et al., Med. Sci. Res. (1987) 15:1443-1444). For instance, 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one, as well as Androsta-4,16-dien-3-one, have been found at different concentrations in the peripheral blood, saliva and axillary secretions of men and of women (Kwan, T. K., et al., Med. Sci. Res. (1987) 15:1443-1444), and their function as a human pheromone, to the extent of affecting choice and judgment, has been suggested (Id. see also Gower, et al., "The Significance of Odorous Steroids in Axillary Odour", In, Perfumery, pp. 68-72, Van Toller and Dodds, Eds., Chapman and Hall, 1988); Kirk-Smith, D. A., et al., Res. Comm. Psychol. Psychiat. Behav. (1978) 3:379). Androstenol (5.alpha.-androst-16-en-3.alpha.-ol) has been claimed to exhibit a pheromone-like activity in a commercial men's cologne and women's perfume (Andron.TM. for men and Andron.TM. for women by Jovan). Japanese Kokai No.
394 Steroids
2295916, refers to perfume compositions containing androstenol and/or its analogues. Androstadien-3.beta.-ol (and perhaps the 3.alpha.-ol) has also been identified in human axillary secretion (Gower, et al., supra, at 57-60). On the other hand, there is little agreement in the literature as to whether or not any putative pheromone actually plays any role in the sexual or reproductive behavior of mammals, particularly of humans. See: Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", In: Mammalian Olfaction, Reproductive Processes and Behavior, Doty, R. L., Ed., Academic Press, 1976). See also: Gower, et al., supra at 68-73. Web site: http://www.delphion.com/details?pn=US06066627__ •
Steroids as neurochemical stimulators of the VNO to alleviate pain Inventor(s): Berliner; David L. (San Mateo County, CA), Monti-Bloch; Luis (Salt Lake City, UT) Assignee(s): Pherin Pharmaceuticals, Inc. (Menlo Park, CA) Patent Number: 6,331,534 Date filed: August 28, 1997 Abstract: The invention relates to a method of alleviating pain. The method comprises nasally administering a steroid which is a human vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Excerpt(s): This invention relates generally to methods for alleviating pain. The present invention relates to certain steroids, and methods of using these steroids as human vomeropherins in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g., the reduction of anxiety. Ohloff, G. et al. (Helv. Chim. Acta (1983) 66:192-217), which is incorporated herein by reference, have shown that several steroids (androstenes) have an odor which varies with different isomeric, diastereomeric, and enantiomeric forms. Some members of this group have been reported to act as a pheromone in some mammalian species--for instance, 5.alpha.androst-16-en-3-one and 5.alpha.-androst-16-en-3.alpha.-ol in pigs (Melrose, D. R., et al., Br. vet. J. (1971) 127:497-502). These 16-androstenes produced by the boar induce mating behavior in estrus sows (Claus, et al., Experimentia (1979) 35:1674-1675). Some studies have noted that, in some species, various characteristics of certain 16-androstenes (including 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-l6-en-3-one), such as concentration, metabolism, and localization, are sexually dimorphic (Brooksbank et al., J. Endocr. (1972) 52: 239-251; Claus, et al., J. Endocr. (1976) 68:483-484; Kwan, et al., Med. Sci. Res. (1987) 15:1443-1444). For instance, 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one, as well as Androsta-4,16-dien-3-one, have been found at different concentrations in the peripheral blood, saliva and axillary secretions of men and of women (Kwan, T. K., et al., Med. Sci. Res. (1987) 15:1443-1444), and their function as a human pheromone, to the extent of affecting choice and judgment, has been suggested (Id. see also Gower, et al., "The Significance of Odorous Steroids in Axillary Odour", In, Perfumery, pp. 68-72, Van Toller and Dodds, Eds., Chapman and Hall, 1988); Kirk-Smith, D. A., et al., Res. Comm. Psychol. Psychiat. Behav. (1978) 3:379). Androstenol (5.alpha.-androst-16-en-3.alpha.-ol) has been claimed to exhibit a pheromone-like activity in a commercial men's cologne and women's perfume (Andron.TM. for men and Andron.TM. for women by Jovan). Japanese Kokai No. 2295916, refers to perfume compositions containing androstenol and/or its analogues.
Patents 395
Androstadien-3.beta.-ol (and perhaps the 3.alpha.-ol) has also been identified in human axillary secretion (Gower, et al., supra, at 57-60). On the other hand, there is little agreement in the literature as to whether or not any putative pheromone actually plays any role in the sexual or reproductive behavior of mammals, particularly of humans. See: Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", In: Mammalian Olfaction, Reproductive Processes and Behavior, Doty, R. L., Ed., Academic Press, 1976). See also: Gower, et al., supra at 68-73. Web site: http://www.delphion.com/details?pn=US06331534__ •
Steroids as neurochemical stimulators of the VNO to alleviate symptoms of PMS and anxiety Inventor(s): Jennings-White; Clive L. (Salt Lake City, UT), Berliner; David L. (Atherton, CA), Adams; Nathan W. (Salt Lake City, UT), Monti-Bloch; Luis (Salt Lake City, UT) Assignee(s): Pherin Corporation (Menlo Park, CA) Patent Number: 6,057,439 Date filed: July 23, 1996 Abstract: The invention relates to a method of alleviating the symptoms of PMS and anxiety. The method comprises nasally administering a steroid which is a human vomeropherin, such that the vomeropherin binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Excerpt(s): This invention relates generally to methods for alleviating symptoms of PMS and anxiety. The present invention relates to certain steroids, and methods of using these steroids as human vomeropherins in order to alter hypothalamic function, thereby affecting certain consequent behavior and physiology, e.g., the reduction of anxiety. Ohloff, G. et al. (Helv. Chim. Acta (1983) 66:192-217), which is incorporated herein by reference, have shown that several steroids (androstenes) have an odor which varies with different isomeric, diastereomeric, and enantiomeric forms. Some members of this group have been reported to act as a pheromone in some mammalian species--for instance, 5.alpha.-androst-16-en-3-one and 5.alpha.-androst-16-en-3.alpha.-ol in pigs (Melrose, D. R., et al., Br. vet. J. (1971) 127:497-502). These 16-androstenes produced by the boar induce mating behavior in estrus sows (Claus, et al., Experimentia (1979) 35:1674-1675). Some studies have noted that, in some species, various characteristics of certain 16-androstenes (including 5.alpha.-Androst-16-en-3.alpha.-ol and 5.alpha.Androst-16-en-3-one), such as concentration, metabolism, and localization, are sexually dimorphic (Brooksbank et al., J. Endocr. (1972) 52: 239-251; Claus, et al., J. Endocr. (1976) 68:483-484; Kwan, et al., Med. Sci. Res. (1987) 15:1443-1444). For instance, 5.alpha.Androst-16-en-3.alpha.-ol and 5.alpha.-Androst-16-en-3-one, as well as Androsta-4,16dien-3-one, have been found at different concentrations in the peripheral blood, saliva and axillary secretions of men and of women (Kwan, T. K., et al., Med. Sci. Res. (1987) 15:1443-1444), and their function as a human pheromone, to the extent of affecting choice and judgment, has been suggested (Id. see also Gower, et al., "The Significance of Odorous Steroids in Axillary Odour", In, Perfumery, pp. 68-72, Van Toller and Dodds, Eds., Chapman and Hall, 1988); Kirk-Smith, D. A., et al., Res. Comm. Psychol. Psychiat. Behav. (1978) 3:379). Androstenol (5.alpha.-androst-16-en-3.alpha.-ol) has been claimed to exhibit a pheromone-like activity in a commercial men's cologne and women's perfume (Andron.TM. for men and Andron.TM. for women by Jovan). Japanese Kokai No. 2295916, refers to perfume compositions containing androstenol and/or its
396 Steroids
analogues. Androstadien-3.beta.-ol (and perhaps the 3.alpha.-ol) has also been identified in human axillary secretion (Gower, et al., supra, at 57-60). On the other hand, there is little agreement in the literature as to whether or not any putative pheromone actually plays any role in the sexual or reproductive behavior of mammals, particularly of humans. See: Beauchamp, G. K., et al., "The Pheromone Concept in Mammalian Chemical Communication: A Critique", In: Mammalian Olfaction, Reproductive Processes and Behavior, Doty, R. L., Ed., Academic Press, 1976). See also: Gower, et al., supra at 68-73. Web site: http://www.delphion.com/details?pn=US06057439__ •
Steroids with radical-attracting aromatic substituents, process for the production thereof and pharmaceutical compounds containing the said substances Inventor(s): Droescher; Peter (Weimar, DE), Menzenbach; Bernd (Jena, DE), Ponsold; Kurt (Jena, DE), Undeutsch; Bernd (Jena, DE), Oettel; Michael (Jena, DE), Romer; Wolfgang (Jena, DE), Kaufmann; Gunter (Jena, DE), Schroder; Jens (Jena, DE) Assignee(s): Jenapharm GmbH & Co. KG (Jena, DE) Patent Number: 5,977,096 Date filed: February 20, 1999 Abstract: Novel substituted steroid compounds are disclosed which are more effective than known radical-trapping agents in methods of prophylaxis and therapy of radicalmediated cell damage and of treatment of diseases due to radical-mediated cell damage. The novel substituted steroid compounds can be made from steroids having an estrane, androstane, pregnane or cholestane basic skeleton and have a radical-attracting aromatic substituent of the general formula --(CH.sub.2).sub.n X, or.dbd.CH--(CH.sub.2).sub.m X at the 17 or 6 position of the steroid nucleus, wherein X=Y, OY, SY, SeY or NHY; n=0 to 5; m=n-1 and Y is a phenyl group having five substituents A, B, C, D and E, wherein A to E is independently H, alkyl, Oalkyl, Oacyl, OH, or one of the substituents B, C or D is NR.sub.2 wherein R=alkyl and each of the other substituents is hydrogen. Pharmaceutical compositions containing the novel substituted steroid compounds and methods of making them are also part of the invention. Excerpt(s): The invention relates to novel steroids with radical-attracting aromatic substituents, processes for their production, and medications containing these compounds for the prophylaxis and therapy of radical-mediated cell damage. From professional and patent literature it is known that reactive oxygen species (ROSs), free oxygen radicals and other radial forms play an important role in the occurrence of many kinds of cell damage, such as ischemic and traumatic organ injuries, and inflammatory and toxic processes. A negative effect of ROSs, free oxygen radicals and other forms of radicals can also be found in brain and spinal column injuries, shock states, stroke, muscular dystrophy, emphysemas, adult respiratory distress syndrome (ARDS), asthma, aging processes, in tissue damage after myocardial infarction, damage from toxic processes and radiation, burns, and transplant-dictated immune reactions. Among other factors, lipid peroxidation and the oxidation of low-density lipoprotein (LDL) cholesterol, combined with irreversible membrane and endothelial damage are the starting point for such radical-mediated cell damage. Web site: http://www.delphion.com/details?pn=US05977096__
Patents 397
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Synthesis of 16-unsaturated pregnanes from 17-keto steroids Inventor(s): Hessler; Edward J. (Kalamazoo, MI), VanRheenen; Verlan H. (Portage, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,216,159 Date filed: May 25, 1978 Abstract: 17-Keto steroids (I) in their protected form (IIa or IIb) are reacted with a metalated olefin (VI) to give a 21-aldehyde (IV) which is readily transformed to a 16unsaturated pregnane (V) which is useful in the production of commercially important substituted corticoids. Excerpt(s): Various processes are known for the production of 21-hydroxypregna-4,16diene-3,20-diones. U.S. Pat. No. 3,839,369 claims a process for preparing a 21hydroxypregna-4,9(11),16-triene-3,20-dione-type steroid by heating the corresponding 17-nitrate ester. The present invention does not go thru a 17.alpha.-hydroxy steroid or involve a nitrate ester. U.S. Pat. No. 3,493,563 discloses a process for preparing a 21hydroxypregna-4,9(11),16-triene-3,20-dione-type steroid by dehydrating with thionyl chloride or phosphorus oxychloride the corresponding 17.alpha.,21-dihydroxy-20-keto steroid. The process of the present invention introduces the double bond at C-16 during the addition of the two carbon side chain at C-17 starting with an androstenedione-type steroid. Web site: http://www.delphion.com/details?pn=US04216159__
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Synthesis of A-ring aromatic steroids Inventor(s): Cohen; Noal (Montclair, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 3,933,870 Date filed: September 30, 1974 Abstract: Total synthesis of steroids of the estrone and equilenin series involving conjugate 1,4-addition of a meta-substituted benzyl organometallic reagent to a C/D bicyclic methylene ketone. An aromatization of the B-ring of.DELTA. 9(11) estrone derivatives. Excerpt(s): The present invention relates to a process for the preparation of steroids starting with a C/D bicyclic intermediate. In particular, the types of steroids which may be synthesized by means of the present process are those having an aromatic A-ring such as estrone, estrone methyl ether, and so forth; and those steroids having both the A and B-ring aromatic such as equilenin and equilenin methyl ether. Aromatic steroids such as those aforementioned are naturally occurring hormones which possess a wide range of biological activity and are also useful for the preparation of other compounds of the steroid type, for example, 19-norsteroids. As used throughout the specification and the appended claims, the term "lower alkyl" denotes a saturated group consisting solely of carbon and hydrogen having a straight chain of from 1 to 8 carbon atoms. Examples of such groups are methyl, ethyl, butyl, hexyl, octyl, and the like. The term "tertiary lower alkyl" denotes a saturated group consisting solely of carbon and hydrogen having its valence from a carbon bound to three other carbon atoms. Examples of such groups include tertiary butyl, tertiary amyl, and so forth. The term "halogen" refers to chlorine, bromine and iodine and the term "halide" refers to the
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negative ions thereof. The term "lower alkylene" refers to a divalent saturated hydrocarbon group having its two valences to two different groups. Examples of such groups are methylene, ethylene, 1,2-propylene, 1,3-propylene, 1,4-butylene, 1,5pentylene, and so forth. In the formulae presented herein, the relative stereochemistry of the various substituents on the cyclic nucleus is indicated by one of three notations: a solid line ( ), indicating the substituent is in the.beta.-orientation, i.e., above the plane of the molecule: a dotted line ( ), indicating the substituent is in the.alpha.-orientation, i.e., below the plane of the molecule; or a wavy line ( ), indicating the substituent may be either in the.alpha.- or.beta.-configuration or may be a mixture of both. Web site: http://www.delphion.com/details?pn=US03933870__ •
Synthesis of steroids Inventor(s): Kaiser; Emil T. (5634 S. Woodlawn Ave., Chicago, IL 60637) Assignee(s): none reported Patent Number: 4,163,744 Date filed: February 10, 1978 Abstract: The synthesis of 1.alpha.,25-dihydroxycholesterol, 1.alpha.,25-dihydroxy-7dehydrocholesterol and 1.alpha.,25-dihydroxycholecalciferol and other sterol derivatives from bile acids. Also the synthesis of 3,6-diketo steroids useful in the production of 1.alpha.,25-dihydroxycholesterol and other sterols which are biologically active or can be converted to biologically active sterols. The invention involves the sterols so produced and the processes by which they are prepared. Excerpt(s): This invention relates to the synthesis of steroids and more particularly to the synthesis of 1.alpha.,25-dihydroxycholesterol and to precursor steroids and derivatives thereof. Vitamin D.sub.3 (cholecalciferol) has been known for many years. It may be prepared from cholesterol by the introduction of an additional bond into the cholesterol molecule to produce 7-dehydrocholesterol and subjecting the 7-dehydrocholesterol to ultraviolet radiation. It was at one time thought to be biologically active in the regulation of intestinal calcium transport and the mobilization of calcium from bone. More recently it has been discovered that to be biologically active cholecalciferol has to be hydroxylated in the body to 25-hydroxycholecalciferol or hydroxylated derivatives thereof, particularly 1.alpha.,25-dihydroxycholecalciferol. It would, therefore, be important to prepare and administer such hydroxylated derivatives, particularly 1.alpha.,25-dihydroxycholecalciferol, instead of Vitamin D.sub.3. The synthesis of 25hydroxycholesterol, a precursor of 25-hydroxycholecalciferol, by practical methods is set forth in my co-pending patent applications Ser. No. 816,478 filed July 18, 1977 and Ser. No. 829,009 filed Aug. 30, 1977, now U.S. Pat. No. 4,134,904. It would now be important indeed to discover practical and effective methods for the synthesis of 1.alpha.,25dihydroxycalciferol and its derivative 1.alpha.,25-dihydroxycholecalciferol. Web site: http://www.delphion.com/details?pn=US04163744__
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Synthesis of steroids Inventor(s): Johnson; William S. (Portola Valley, CA), Bunes; Leonard A. (San Carlos, CA) Assignee(s): The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) Patent Number: 4,219,489 Date filed: September 5, 1978 Abstract: Method and compounds are provided for use in the synthesis of steroids wherein a polyolefin is provided having an initiating group having a chalcogen atom in juxtaposition to a double bond, so as to be capable of bond formation to close to form a ring and having a terminating group involving pi unsaturation (a double or triple bond) conjugated to an aromatic ring. Upon acid catalysis, sigma bonds are formed through the interaction of a carbocation formed at the carbon atom bonded to the chalcogen atom and the double bond intermediate the initiating group and the terminating group, which close to form rings of a steroid nucleus, the carbocation interacting with the pi unsaturation conjugated with the aromatic group and being captured by a nucleophile present in the acidic reaction medium. The resulting steroid product may then be modified in known ways to produce known steroids. Excerpt(s): Steroids play an important role in life processes being the basic structure for the male and female hormones, corticosteroids and bile acids, as well as the basis for many synthetic reagents, such as synthetic male and female hormones, antiinflammatory agents, and the like. The naturally occurring steroids which the synthetic steroids normally mimic have a complex polycyclic structure with particular geometry as to the ring fusions, as well as substituents on the ring, and also have a specific stereoisomerism. Any synthesis must therefore recognize the need to provide a product having the required geometry and stereochemistry. For the most part the industry has relied on the use of naturally occurring plant steroids which were then modified to provide the necessary substituents. Many of the procedures were fairly extensive since the plant steroids did not provide readily available functionalities at desired sites, such as C-11, nor at sites adjacent to C-11 which would allow for introduction of a particular functionality. In addition, the plant steroids were only difficultly modifiable, where hydrocarbon groups, such as angular methyl groups were modified, either by introducing a polar functionality, or by changing the alkyl group. In developing a complete synthesis from small molecules to a steroid structure there are a number of considerations. Desirably, resolution which allows for subsequent asymmetric induction should be afforded relatively early in the synthesis. Reactions in the course of the synthesis should not adversely affect earlier geometry. Formation of functionalities should afford the desired spatial configuration upon cyclization. Therefore, a synthetic scheme must be considered as a single entity, in that earlier synthetic steps must anticipate subsequent synthetic steps, and subsequent synthetic steps must take into account their effect on functionalities which have been previously introduced. Web site: http://www.delphion.com/details?pn=US04219489__
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Synthesis of steroids Inventor(s): Kaiser; Emil T. (5634 S. Woodlawn Ave., Chicago, IL 60637) Assignee(s): none reported Patent Number: 4,354,972 Date filed: August 10, 1981 Abstract: This invention relates to the synthesis of steroids which are useful for their biological activity or which may be converted to steroids which have such activity. These syntheses include the steroid compounds and processes for their preparation.An object of the invention is to provide syntheses which are applicable to materials which are readily available in good supply for converting such materials to steroids which are useful and desirable in the manufacture of pharmaceutical products.More particularly, I have sought to discover processes and intermediate compounds useful in the synthesis of 24, 25-dihydroxycholesterol from hyodeoxycholic acid or lithocholic acid which are constituents of, and readily available from, animal bile. Excerpt(s): In my U.S. Pat. Nos. 4,134,905; 4,163,744; 4,174,345; 4,183,852 and 4,217,279, I describe syntheses for the preparation of 25-hydroxycholesterol and its derivatives from 24-carbon-24-alcohol steroids with protected 3- and 6-hydroxyl or ketone groups. Included in these syntheses is the extension of the side chain of the 24-carbon-24-alcohol steroid with a cyano group to a 25-carbon steroid. Steroid aldehydes have been prepared by ozonization of dibromostigmasterol acetate to yield 3-acetoxy-bis 5cholenaldehyde and from thiol esters of deoxycholic acid, 3.beta.-hydroxy-5-cholenic and -bisnor-5-cholenic acid to yield the corresponding steroid aldehydes, by desulfurizing said thiol esters with Raney nickel. These procedures were described in the following publications: A. P. Certolella et al, JACS, 70, 2953 (1948); R. H. Levine et al, ibid, 70, 511 (1948); G. B. Spero et al, ibid, 70, 1907 (1948); and A. V. McIntosh et al, ibid, 70, 2955 (1948). By the present invention, I now transform the 24-carbon-25-alcohol steroids into 24-carbon-24-aldehydes by procedures which do not oxidize the 24position beyond the aldehyde stage and do not affect the protecting groups of the 3- and 6-functions. The 24-carbon steroid 24-aldehydes may be used as intermediates for the production of 24, 25-dihydroxycholecalciferol and 1, 24, 25-trihydroxycholecalciferol, hydroxylated vitamin D.sub.3 useful for the treatment of calcium metabolism disorders. Web site: http://www.delphion.com/details?pn=US04354972__
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Tin steroids and their use as antineoplastic agents Inventor(s): Cardarelli; Nathan F. (Akron, OH), Kanakkanatt; Sebastian V. (Akron, OH) Assignee(s): Unique Technologies, Inc. (Akron, OH) Patent Number: 4,541,956 Date filed: July 28, 1983 Abstract: A method and composition for the preparation of steroid compounds by the reaction of various organotin compounds with steroids. Said compounds retard the growth of malignant tumors and, in some cases, completely destroy the tumor. Excerpt(s): The present invention relates to a composition of, and preparation of, tin steroids, and their use as antineoplastic agents. Heretofore, with regard to the treatment of malignant growths such as various types of cancer, and the like, the general approach of the medical and pharmaceutical professions has been keyed to the discovery of the
Patents 401
causitive agents. The general approach by the pharmaceutical and medical industry has been to determine the nature of such agents, study the mechanism involved, and then create a pharmaceutical material that will intervene that mechanism. It has now been discovered by the inventors that the thymus gland of mammals contains tin. Moreover, it has further been discovered that the thymic tin compounds are in steroid form, and that tin steroids retard the growth of and and even kill malignant tumors or prevent cancerous proliferation. Web site: http://www.delphion.com/details?pn=US04541956__ •
Tin steroids and their uses Inventor(s): Cardarelli; Nathan F. (439 Crestwood Ave., Akron, OH 44302), Kanakkanatt; Sebastian V. (2459 Audubon Rd., Akron, OH 44320) Assignee(s): none reported Patent Number: 4,634,693 Date filed: August 12, 1985 Abstract: Tin steroids and methods of using the same. The tin steroid compounds are prepared by the reaction of various organotin compounds with various steroids. Said compounds inhibit the growth of malignant tumors. They are also useful as insecticides, larvicides, bactericides and fungicides. Excerpt(s): The present invention relates to a composition of, and preparation of, tin steroids, and their use as antineoplastic agents, bacteriacides, fungicides and insecticides. Heretofore, with regard to the treatment of malignant growths such as various types of cancer and the like, the general approach of the medical and pharmaceutical professions has been keyed to the discovery of the causitive agents. The general approach by the pharmaceutical and medical industry has been to determine the nature of such agents, study the mechanism involved, and then create a pharmaceutical material that will intervene that mechanism. It has now been discovered that the thymus gland of mammals processes exogenous tin into several biochemical compounds of a steroidal nature. Such tin steroids function as a critical component of the immune system, being involved in surveillance, detection and destruction of cells inimical to the well being of the host. Synthetic tin steroids, a hitherto unknown class of compounds have been prepared and found to be biologically highly active against mammalian tumors and tumor cells, pathogenic bacteria, and fungi. Furthermore, it has been discovered that select tin steroids interfere in the life processes of insects of public health and agricultural importance, and will destroy said insects directly through toxic activity, or indirectly by preventing metamorphosis, and in some instances acting as antifeedants. Web site: http://www.delphion.com/details?pn=US04634693__
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Topically administrable pharmaceutical compositions containing anti-inflammatory steroids Inventor(s): Busse; Michael J. (Harrow, GB2), Lees; Kenneth A. (Northwood, GB2) Assignee(s): Glaxo Group Limited (London, GB2) Patent Number: 4,370,322 Date filed: October 5, 1981 Abstract: Pharmaceutical compositions such as ointments and creams are provided by admixture of anti-inflammatory steroids active on topical application with a liquid oily phase containing at least one oil possessing a viscosity less than 10 centistokes and in which the steroid has a solubility of at least 0.5% by weight at 25.degree. C., the degree of unsaturation of the steroid in the liquid oily phase of the composition at 25.degree. C., being at least 3. Examples of steroids which may be used are betamethasone, beclomethasone and clobetasol derivatives. Suitable oils include esters of mono- and dibasic aliphatic acids. The compositions may include further oils such as liquid paraffin and conventional additives used in the preparation of ointments and creams. The local anti-inflammatory effect of the steroids is maintained in such formulations but systemic side effects are decreased. Excerpt(s): The present invention relates to novel pharmaceutical compositions containing anti-inflammatory steroids. Anti-inflammatory steroids such as clobetasol 17propionate are commonly formulated for topical application in solution in relatively polar solvents such as propylene glycol which, in the case of ointments, may be dispersed in white soft paraffin. Such formulations permit some penetration of the active steroid into the skin to exert a topical anti-inflammatory effect. It is thought to be particularly important that the steroid should not, however, be so completely absorbed that it can exert a systemic effect which would be likely to lead to the various unwanted side effects observed with anti-inflammatory steroids such as cortisol suppression. The use of isopropyl and butyl adipates as well as of ethyl lactate and ethanol as vehicles for the topical formulation of triamcinolone acetonide and its dicoumaryl ester is described in a paper by Altmeyer and Zaun in Arch. Derm. Forsch 1974, 248, 387-390. The effects of these vehicles on the vasoconstrictor properties of the compounds is discussed, and it is concluded that the base in which a corticosteroid is administered determines to a great extent its penetration rate, strength and duration of topical anti-inflammatory activity. There is no discussion, however, of the possible dangers of enhanced penetration in increasing systemic absorption. As far as can be determined, the solutions of triamcinolone acetonide concerned were saturated or even supersaturated which we believe would have tended to maximise release of the steroid into the aqueous body fluids. Web site: http://www.delphion.com/details?pn=US04370322__
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Total synthesis of 11-alkyl steroids Inventor(s): Garland; Robert B. (Northbrook, IL), Pappo; Raphael (Skokie, IL) Assignee(s): G. D. Searle & Co. (Chicago, IL) Patent Number: 3,962,291 Date filed: September 5, 1974
Patents 403
Abstract: A novel total synthesis of 11-alkyl steroids, utilizing readily available and inexpensive raw materials, is described. The resulting products are useful and novel pharmacological agents possessing, for example, selective hormonal properties. Excerpt(s): The present invention is concerned with a novel total synthesis of 11-alkyl steroids and with novel 11-alkyl steroids produced thereby. These novel compounds are particularly useful in consequence of their valuable pharmacological properties, e.g. progestational, and possess the further advantage of exhibiting minimal undesirable hormonal side-effects, e.g. estrogenic. The term lower alkyl radical comprehends those groups containing up to and including 7 carbon atoms and is exemplified by methyl, propyl, pentyl, heptyl and the corresponding branched-chain radicals. Representative of the 1-alkynyl radicals comprehended are ethynyl, 1-propynyl, 1-hexynyl, 1-heptynyl and the branched-chain isomeric groups corresponding. Web site: http://www.delphion.com/details?pn=US03962291__ •
Transdermal therapeutic systems that contain sex steroids and dimethyl isosorbide Inventor(s): Lipp; Ralph (Berlin, DE), Gunther; Clemens (Berlin, DE), Riedl; Jutta (Berlin, DE), Tauber; Ulrich (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin, DE) Patent Number: 5,904,931 Date filed: November 8, 1996 Abstract: Transdermal therapeutic systems that contain sex steroids and optionally penetration-enhancers and crystallization inhibitors are described, which are characterized in that they contain dimethyl isosorbide, with the exception of systems that contain active ingredient-containing, non-free-flowing gel phases or 3-ketodesogestrel. Excerpt(s): The invention relates to transdermal therapeutic systems that contain sex steroids and optionally penetration-enhancers and crystallization inhibitors, which are characterized in that they contain dimethyl isosorbide, with the exception of systems that contain active ingredient-containing, non-free-flowing gel phases or 3-ketodesogestrel. According to the invention, sex steroids are to be defined preferably as gestagens and/or estrogens although, in principle, other sex steroids, such as androgens, antiestrogens or antigestagens, are suitable for the production of the agent according to the invention. Suitable gestagens for the agent according to the invention are, for example, gestodene, levonorgestrel, desogestrel, norethisterone and norethisterone acetate. For the production of the agent according to the invention, 3keto-desogestrel is also suitable, as indicated by PCT/EP93/02224, which had not yet been prepublished as of the time of priority of this application. Web site: http://www.delphion.com/details?pn=US05904931__
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Trialkylsilyl trifluoromethanesulfonate mediated.alpha.-methylenic functionalization of 4-aza-5.alpha.-androstan-3-one steroids
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Inventor(s): King; Anthony O. (Hillsboro, NJ), Anderson; Kevin (Plainsboro, NJ), Karady; Sandor (Mountainside, NJ), Douglas; Alan W. (Monmouth Junction, NJ), Abramson; Newton L. (Edison, NJ), Shuman; Richard F. (Westfield, NJ) Assignee(s): Merck & Co., Inc. (NJ) Patent Number: 5,187,278 Date filed: November 1, 1991 Abstract: A novel single-pot trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si-OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the.alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the.alpha.-methylene carbon, of.DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase. Excerpt(s): This invention is a single-pot process for trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si-OTf) mediated production of derivatives of 4-aza 3-keto steroids at the.alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the.alpha.-methylene carbon, of the.DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase. The enzyme, 5-.alpha. reductase, is responsible for the local formation within a target organ of 5.alpha.-dihydrotestosterone, which is the principal mediator of androgenic activity in some organs. Inhibitors of testosterone5.alpha.-reductase have been shown to prevent or lessen symptoms of hyperandrogenic stimulation. Nayfe et al., [Steroids, 14, 269 (1969)] demonstrated in vitro that methyl 4androsten-3-one-17.beta.-carboxylate was a testosterone-5.alpha.-reductase inhibitor. Voigt and Hsia, [Endocrinology, 92, 1216 (1973), Canadian Pat. No. 970,692], demonstrated that the above ester and the parent free acid, 4-androsten-3-one-17.beta.carboxylic acid are both active inhibitors of testosterone-5.alpha.-reductase in vitro. Web site: http://www.delphion.com/details?pn=US05187278__ •
Triazinylpiperazinyl steroids Inventor(s): John M. McCall (Kalamazoo, MI), Ayer; Donald E. (Kalamazoo, MI), Jacobsen; E. Jon (Plainwell, MI), Van Doornik; Frederick J. (Hamilton, MI), Palmer; John R. (Kalamazoo, MI), Karnes; Harold A. (Kalamazoo, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 5,380,840 Date filed: December 1, 1992 Abstract: Disclosed are amino substituted steroids (XI) which contain 4-[1,3,5-triazin-2yl]- or 4-[1,2,4-triazin-3-yl]- 1-piperazinyl group attached to the terminal carbon atom of the C.sub.17 -side chain which are useful as pharmaceutical agents for treating a number of conditions. Excerpt(s): The present invention relates to amino substituted steroids which are useful as pharmaceutical agents. Various amino (substituted) steroids are known with the amine substitution on either the steroidal ring system or on the side chain of the D-ring
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at C.sub.17. U.S. Pat. No. 4,456,602 discloses steroidal 21-esters in which there is an amino function in the non-steroidal portion of the ester. Web site: http://www.delphion.com/details?pn=US05380840__ •
Use of boron supplements to increase in vivo production of hydroxylated steroids Inventor(s): Nielsen; Forrest H. (Grand Forks, ND), Hunt; Curtiss D. (Grand Forks, ND) Assignee(s): The United States of America as represented by the Secretary of (Washington, DC) Patent Number: 4,849,220 Date filed: April 20, 1988 Abstract: The oral administration of boron compounds such as sodium borate and boric acid increases the amounts of hydroxylated steroids in human plasma. This will help prevent or alleviate pathology, such as osteoporosis, caused by suboptimal circulating hydroxylated steroids such as 17.beta.-estradiol and testosterone. Excerpt(s): The previously known effects of boron on animal metabolism have been reviewed by Nielsen ["Trace Elements in Human and Animal Nutrition," Vol. 2, pp. 422427, Academic, New York (1986)]. In 1981, Hunt and Nielsen [In "Trace Element Metabolism in Man and Animals-4," pp. 597-600, Aust. Acad. Sci., Canberra (1981)]reported that boron deprivation depressed growth and elevated alkaline phosphatase activity in chicks fed inadequate cholecalciferol. Cholecalciferol deficiency enhanced the need for boron, and it was postulated that boron might interact with the metabolism of calcium, phosphorus, or magnesium. Further experiments suggested that the influence of boron was the result of altered parathormone activity [F. H. Nielsen, In "Trace Elements in Man and Animals-5 Abstracts," p. 26, Aberdeen, Scotland (1984)]. This hypothesis was also supported by Elsair et al. [Fluoride 15: 30-38 (1980)], who reported that high dietary boron partially alleviated the fluoride-induced secondary hyperparathyroid signs of hypercalcemia in rabbits. Web site: http://www.delphion.com/details?pn=US04849220__
Patent Applications on Steroids As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to steroids:
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This has been a common practice outside the United States prior to December 2000.
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17-methylene steroids, process for their production and pharmaceutical compositions that contain these compounds Inventor(s): Elger, Walter; (Berlin, DE), Hillisch, Alexander; (Jena, DE), Kaufmann, Gunter; (Jena, DE), Muller, Gerd; (Jena, DE), Droescher, Peter; (Weimar, DE), Schweikert, Hans-Udo; (Bonn, DE), Menzenbach, Bernd; (Jena, DE) Correspondence: MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BLVD. SUITE 1400; ARLINGTON; VA; 22201; US Patent Application Number: 20020091112 Date filed: January 25, 2002 Abstract: The invention relates to 17-methylene steroids, process for their production and pharmaceutical compositions that contain these compounds.The compounds according to the invention have a hybrid-type profile of action in the sense that they act as inhibitors of 5.alpha.-reductase and simultaneously as gestagens. They are therefore suitable for treating diseases that are the result of elevated androgen levels in certain organs and tissues in men and women. Together with other hormonal substances, such as an estrogen, testosterone or a strong androgen, the compounds according to the invention are suitable as contraceptive agents for women and for men. Excerpt(s): This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/243,281 filed Oct. 26, 2000. The invention relates to 17methylene steroids, process for their production and pharmaceutical compositions that contain these compounds. The compounds according to the invention have a hybridtype profile of action in the sense that they act as inhibitors of 5.alpha.-reductase and simultaneously as gestagens. They are therefore suitable for treating diseases that are the result of elevated androgen levels in certain organs and tissues in men and women. Together with other hormonal substances, such as an estrogen, testosterone or a strong androgen, the compounds according to the invention are suitable as contraceptive agents for women and for men. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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4-aza-steroids Inventor(s): Pamidi, Chenchaiah C. (Hamilton, CA), Jia, Qi; (Ajax, CA) Correspondence: Nixon & Vanderhye P.C. 1100 North Glebe Road, 8th Floor; Arlington; VA; 22201; US Patent Application Number: 20020035260 Date filed: July 23, 2001 Abstract: 4-Aza-steroid compounds are provided, which have functional groups at one or more of positions 7, 11 and 15, such as hydroxyl or hydroxyl derivative groups. The compounds are active against 5-.alpha.-reductase giving indications of utility in combating prostate cancer. The compounds can be prepared by chemo-enzymatic synthesis from easily available 4-aza-steroids. Excerpt(s): This invention relates to 4-aza-steroids, processes for their preparation, and their pharmaceutical applications. More specifically, the invention relates to novel 4-azasteroids useful both as pharmaceutical agents in the inhibition of the enzyme steroid 5.alpha.-reductase, as intermediates in the preparation of other, novel, pharmaceutically active 4-aza-steroid compounds, and the novel, pharmaceutically active 4-aza-steroids
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preparable therefrom. Finasteride has, since its original introduction, been reported to be less effective in treating BPH than originally expected (R. S. Rittmaster, N. Engl. J. Med., 1994, 330, 120-125). According to reports, there is room for further improvement in the level of residual circulating DHT (20-40%) in patients undergoing treatment with finasteride (G. J. Gormley et. al., J. Clin. Endocrinol. Metab., 1990, 70, 1136-1141). It is now known that there are two isozymes of steroid reductase. The isozyme that principally interacts in skin tissue is conventionally designated as 5-.alpha.-reductase type I (present in rat ventral prostate), while the isozyme that interacts within the prostatic tissue is designated as 5-.alpha.-reductase type II (present in human prostate tissue and rat epididymus). It would be highly desirable to have one drug showing selectivity towards inhibiting 5-.alpha.-reductase type II isozyme, associated with benign prostatic hyperplasia and prostate cancer. It also would be highly desirable to have another drug showing selectivity towards 5-.alpha.-reductase type I isozyme associated with the scalp for use in treatment of male pattern baldness and hirsutism in females. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
AIB1, a novel steroid receptor co-activator Inventor(s): Trent, Jeffrey; (Rockville, MD), Meltzer, Paul; (Rockville, MD) Correspondence: KLARQUIST SPARKMAN, LLP; One World Trade Center; Suite 1600; 121 S.W. Salmon Street; Portland; OR; 97204; US Patent Application Number: 20030153047 Date filed: March 4, 2003 Abstract: The invention features a substantially pure DNA which includes a sequence encoding a novel steroid receptor co-activator which is overexpressed in breast cancer cells, diagnostic assays for steroid hormone-responsive cancers, and screening assays to identify compounds which inhibit an interaction of the co-activator with the steroid hormone. Excerpt(s): Breast cancer arises from estrogen-responsive breast epithelial cells. Estrogen activity is thought to promote the development of breast cancer, and many breast cancers are initially dependent on estrogen at the time of diagnosis. Anti-estrogen compositions have therefore been used to treat breast cancer. A frequent mechanism of increased gene expression in human cancers is amplification, i.e., the copy number of a DNA sequence is increased, in a cancer cell compared to a non-cancerous cell. In breast cancer, commonly amplified regions are derived from 17q21, 8q24, and 11q13 which encode erbB-2, c-myc, and cyclic D1 respectively (Devilee et al., 1994, Crit. Rev. Oncog. 5:247-270). Recently, molecular cytogenetic studies have revealed the occurrence in breast cancers of additional regions of increased DNA copy number (Isola et al., Am. J. Pathol. 147:905-911, 1995; Kallioniemi et al., Proc. Natl. Acad. Sci. USA 91:2156-2160, 1994; Muleris et al., Genes Chromo. Cancer 10:160-170, 1994; Tanner et al., Cancer Research 54:4257-4260, 1994; Guan et al., Nat. Genet. 8:155-161, 1994). Breast cancer is the second leading cause of cancer deaths in American women, and it is estimated that an American woman has at least a 10% cumulative lifetime risk of developing this disease. Early diagnosis is an important factor in breast cancer prognosis and affects not only survival rate, but the range of therapeutic options available to the patient. For instance, if diagnosed early, a "lumpectomy" may be performed, whereas later diagnosis tends to be associated with more invasive and traumatic surgical treatments such as radical mastectomy. The treatment of other cancers likewise is benefitted by early
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diagnosis, for instance the prognosis in the treatment of lung cancer, colorectal cancer and prostate cancers is greatly improved by early diagnosis. There is a need for a simple and reliable method of diagnosis of cancers in general and of breast cancer in particular. There is a need for a method of screening for compounds that inhibit the interaction between an estrogen receptor ER and an ER-dependent nuclear receptor co-activator molecule in order to identify molecules useful in research diagnosis and treatment of cancer. There is also a need for a method for identifying tamoxifen-sensitive cancer patients in order to better manage treatment. A solution to these needs would improve cancer treatment and research and would save lives. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Androgenic steroid compounds and a method of making and using the same Inventor(s): Kepler, John A. (Raleigh, NC), Wani, Mansukh C. (Durham, NC), Cook, C. Edgar; (Staunton, VA), Lee, Yue-Wei; (Chapel Hill, NC) Correspondence: OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20020103177 Date filed: January 22, 2002 Abstract: An androgenic steroid compound of the formula: 1wherein:X, Y, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.5 and R.sup.6 are as defined herein. Excerpt(s): The present invention relates to androgenic steroid compounds and a method of making and using the same. Testosterone is the principal male hormone and is required for the development and maintenance of secondary sexual characteristics, libido and spermatogenesis. Testosterone also has anabolic properties, in promoting in muscle growth and maintenance. Lower than normal testosterone levels in men have been associated with low energy, frailty, depression, decreased libido, weakness, lethargy, loss of lean body and bone mass and impotence. A second androgen, dihydrotestosterone (DHT), is produced from testosterone. DHT is a potent androgen. It is believed to be responsible for prostate growth and inhibitors of the enzyme that forms it have been used to treat prostatic hypertrophy and benign prostate hyperplasia. Testosterone is rapidly metabolized in the body. Since the liver metabolizes most orally administered testosterone before it reaches the systemic blood circulation, large oral doses are necessary in order to have the desired effect. To some extent, this difficulty may be overcome by using the drug in the form of a fatty acid ester and administering the same by intramuscular injection, nevertheless, doses of 200 mg must still be given at weekly or bi-weekly intervals. Although testosterone can be administered by skin patch, large patches must be used due to low activity and rapid metabolism. Recently, a permeation-enhanced back patch was reported, however, this still requires the use of two large, i.e. 37 cm.sup.2 patches for a total area of 11.5 in.sup.2 or about 30% more area than an ordinary playing card. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods Inventor(s): Berliner, David L. (Atherton, CA), Jennings-White, Clive L. (Salt Lake City, UT), Adams, Nathan William; (Salt Lake City, UT) Correspondence: HELLER EHRMAN WHITE & MCAULIFFE LLP; 275 MIDDLEFIELD ROAD; MENLO PARK; CA; 94025-3506; US Patent Application Number: 20020143001 Date filed: August 3, 2001 Abstract: The invention relates to a method of altering hypothalamic function in an individual. The method comprises nasally administering a human semiochemical, e.g. an Androstane steroid, or a pharmaceutical composition containing a semiochemical, such that the ligand semiochemical binds to a specific neuroepithelial receptor. The steroid or steroids is/are preferably administered in the form of a pharmaceutical composition containing one or more pharmaceutically acceptable carriers. Other embodiments of the invention include pharmaceutical compositions containing the steroids. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 07/903,604, filed Jun. 24, 1992, which in turn is a continuation-in-part of U.S. application Ser. No. 07/708,936, filed May 31, 1991, which in turn is a continuation-in-part of U.S. application Ser. No. 07/638,185, filed Jan. 7, 1991, now abandoned. The application also relates to another continuation-in-part of U.S. patent application Ser. No. 07/903,604, U.S. patent appliaction Ser. No. 08/077,359, filed Jun. 15, 1993, and to commonly assigned, co-pending U.S. patent application Ser. No. 07/903,525, filed Jun. 24, 1992 (a continuation-in-part of U.S. application Ser. No. 07/707,862, filed May 31, 1991, which in turn is a continuation-in-part of U.S. application Ser. No. 07/638,743, filed Jan. 7, 1991, now abandoned) entitled "Estrene Steroids as Neurochemical Initiators of Change in Human Hypothalamic Function and Related Pharmaceutical Compositions and Methods"; and to the commonly assigned, co-pending continuation-in-part of Ser. No. 07/903,525, U.S. patent application Ser. No. 08/077,140. The aforementioned U.S. patent applications are each incorporated herein by reference. Finally, this application may relate to a co-pending U.S. patent application entitled "Fragrance Compositions Containing Human Pheromones", filed Mar. 24, 1992, U.S. Ser. No. 07/856,435. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antigestagenically active steroids with a fluorinated 17-alpha-alkyl chain Inventor(s): Neef, Gunter; (Berlin, DE), Schwede, Wolfgang; (Berlin, DE), Schneider, Martin; (Berlin, DE), Klar, Ulrich; (Berlin, DE), Chwalisz, Kristof; (Berlin, DE), Fuhrmann, Ulrike; (Berlin, DE), Heb-Stumpp, Holger; (Berlin, DE), Cleve, Arwed; (Berlin, DE) Correspondence: MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BLVD. SUITE 1400; ARLINGTON; VA; 22201; US Patent Application Number: 20030134834 Date filed: November 27, 2002 Abstract: This invention describes the new 17.alpha.-fluoroalkyl steroids of general formula I 1as well as their physiologically compatible salts with acids and for --
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CO.sub.2R.sup.9 radicals with R.sup.9 meaning hydrogen, as well as their physiologically compatible salts with bases.The new compounds have an extraordinarily strong antigestagenic action and are suitable for the production of pharmaceutical preparations. Excerpt(s): This invention relates to antigestagenically active steroids with a fluorinated 17.alpha.-alkyl chain, process for their production, pharmaceutical preparations that contain the latter and their use for the production of pharmaceutical agents. and for -NR.sup.9aR.sup.9b radicals, as well as their physiologically compatible salts with acids and for --CO.sub.2R.sup.9 radicals with R.sup.9 meaning hydrogen, as well as their physiologically compatible salts with bases. The wavy lines mean that the substituent in question can be in.alpha.- or.beta.-position. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
cDNAs co-expressed with placental steroid synthesis genes Inventor(s): Wong, Sophia Li-Ming; (San Jose, CA), Walker, Michael G. (Sunnyvale, CA) Correspondence: INCYTE CORPORATION (formerly known as Incyte; Genomics, Inc.); 3160 PORTER DRIVE; PALO ALTO; CA; 94304; US Patent Application Number: 20030170627 Date filed: November 27, 2001 Abstract: The invention provides novel cDNAs that coexpress with known placental steroid synthesis genes. The invention also provides expression vectors, host cells, proteins encoded by the cDNAs and antibodies which specifically bind the proteins. The invention also provides methods for the diagnosis, prognosis, evaluation of therapies and treatment of disorders associated with steroid-responsive tissues and with pregnancy. Excerpt(s): This application claims the benefit of provisional application No. 60/253,425, filed Nov. 27, 2000. The invention relates to cDNAs identified by their coexpression with known placental steroid synthesis genes and to their use in the diagnosis, prognosis, treatment, and evaluation of therapies for disorders associated with steroid-responsive tissues and with pregnancy. During pregnancy, the placenta is the primary source of the steroid hormones, estrogen and progesterone (Nestler 1990). The cells and tissues of the placenta express a variety of genes that regulate or participate in steroid synthesis. These include aromatase P-450, cholesterol side-chain cleavage enzyme, meltrin-L, placental lactogen hormone, pregnancy-associated plasma protein-A, hydroxysteroid dehydrogenase, pregnancy-specific beta-glycoprotein, and placental alkaline phosphatase. The expression of these genes and the proteins which they encode play an important role in pregnancy, both in the normal development of the fetus and in disorders which affect the fetus and/or the mother, particularly pregnancy-induced hypertension (PIH) and preeclampsia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for demonstrating secretory immune system regulation of steroid hormone responsive cancer cell growth Inventor(s): Sirbasku, David A. (Houston, TX) Correspondence: CONLEY ROSE & TAYON, P.C. P. O. BOX 3267; HOUSTON; TX; 77253-3267; US Patent Application Number: 20020012954 Date filed: May 10, 2001 Abstract: Serum-containing and serum-free immunoglobulin inhibitors of steroid hormone responsive cancer cell growth are disclosed, along with their methods of production. Also disclosed are defined cell culture media, assay protocols, and model systems using the inhibitors for demonstrating steroid hormone growth effects of natural and synthetic substances, and other cell culture applications. The disclosed compositions and methods employing the immunoglobulin inhibitors are also useful as reagents in research, and for the diagnosis, treatment and prevention of mucus epithelial cancers. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn. 119(e) of U.S. Provisional Patent Application Nos. 60/203,314 filed May 10, 2000; 60/208,348 filed May 31, 2000; 60/208,111 filed May 31, 2000; 60/229,071 filed Aug. 30, 2000 and 60/231,273 filed Sep. 8, 2000. The present invention generally relates to the regulation of steroid hormone responsive cancer cell growth, and more particularly to compositions and in vitro methods and models for demonstrating secretory immune system immunoglobulin regulation of mucosal epithelial cancer cell growth. In 1896, a physician named Beatson reported in the medical journal Lancet (Beatson G T (1896) Lancet (Part 1, July 11), 104-107 and Lancet (Part 2, July 18), 162-165) that removal of the ovaries from breast cancer patients slowed or stopped the growth of their tumors. As medical science has moved forward, it is now understood that Dr. Beatson had found that the estrogens made by the ovaries promoted the growth of breast cancers. In the 1940s and 1950s, work by Professor Charles Huggins (Huggins C B and Hodges C V (1941) Cancer Res 1, 293-297; Huggins et al. (1941) Arch Surg 43, 209-223) proved that surgical or chemical castration very substantially reduced the growth of prostate cancers. These results indicated that testicular androgens were important promoters of the growth of tumors of this male accessory organ. In subsequent work, researchers have established that estrogens and androgens act on breast and prostate cancer cells via receptors within the cell nucleus (Tsai M-J and O'Malley B W (1994) Annu Rev Biochem 63, 451-486; Evans R E (1988) Science (Wash D.C.) 240, 889-895). In fact, estrogen receptors are now commonly measured in breast cancer specimens to assist in decisions regarding the most effective therapies for each patient, and chemical and surgical castration are common treatments for prostate cancer. The regulation of estrogen target tissue cell growth has been a topic of dynamic experimental interest for several years (Jensen E V and DeSombre E R (1973) Science (Wash D.C.) 182, 126-134; O'Malley B W and Means A R (1974) Science (Wash D.C.) 183, 610-620). Today, it is generally accepted that estrogen interaction with specific nuclear located DNA binding receptors is necessary to initiate critical cell cycle events (Dickson R B and Stancel G M (2000) J Natl Cancer Inst Monogr No 27, 135-145). It is also highly likely that other non-steroid factors are essential participants in this process (Sirbasku D A (1978) Proc Natl Acad Sci USA 75, 3786-3790; Sirbasku D A (1981) Banbury Report 8, 425-443; Dickson R B and Lippman M E (1987) Endocr Rev 8, 2943; Soto A M and Sonnenschein C (1987) Endocr Rev 8, 44-52). Many of these new regulators fall into the general class of positive acting substances called growth factors (Gospodarowitz D and Moran J S (1976) Annu Rev
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Biochem 45, 531-558; Goustin A S et al. (1986) Cancer Res 46, 1015-1029). Simply stated, these agents cause cells to undergo cell division and thereby lead to growth. Because the hallmark of cancer is uncontrolled cell division, understanding these molecules and how they act is of vital importance. Other members of this regulatory family include negative acting agents called growth inhibitors (Knabbe et al. (1987) Cell 48, 417-428; de Jong J S et al. (1998) J Pathol 184, 44-52). They block cell division, and because of this, are important targets for new anticancer therapies. A great deal of study has focused on cellular site(s) of estrogen action, and various models have been proposed attempting to explain how estrogen participates with these additional factors to regulate growth. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for the diagnosis, treatment and prevention of steroid hormone responsive cancers Inventor(s): Sirbasku, David A. (Houston, TX) Correspondence: CONLEY ROSE & TAYON, P.C. P. O. BOX 3267; HOUSTON; TX; 77253-3267; US Patent Application Number: 20020006630 Date filed: May 10, 2001 Abstract: Compositions and methods that use the body's natural secretory immune system in a new way against steroid hormone responsive tumors of the breast and prostate, as well as other glandular/mucus epithelial tissues such as colon, ovary, endometrium, kidney, bladder, stomach, pancreas and secretory pituitary gland are provided. Also provided are new ways of identifying carcinogenic, or potentially carcinogenic, bacteria in a tissue or body fluid to provide better anti-cancer therapies and preventatives than have been available previously. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn. 119(e) of U.S. Provisional Patent Application No. 60/203,314 filed May 10, 2000; 60/208,348 filed May 31, 2000; 60/208,111 filed May 31, 2000; 60/229,071 filed Aug. 30, 2000; and 60/231,273 filed Sep. 8, 2000. The present invention generally relates to risk assessment, detection, diagnosis, prognosis, treatment and prevention of steroid hormone responsive cancers of mucosal epithelial tissues (i.e., glands and tissues that secrete or are bathed by secretory immunoglobulins). More particularly, the invention relates to negative (inhibitory) regulation of steroid hormone responsive cancer cell proliferation, and to the immunoglobulin inhibitors and the receptors that mediate such regulation. Finding a naturally occurring biochemical defense mechanism capable of controlling neoplastic growth has been the goal of a number of researchers for many years. Use of the immune system against malignant tumors forms the basis for many anti-cancer strategies. For example, U.S. Pat. No. 5,980,896 describes certain antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins directed against human carcinoma cells. Conventional anti-tumor immunotherapies rely on antibody-antigen recognition chemistry, and on targeting of antibodies against various antigenic features of tumor cells in order to trigger destruction of the tumor cells by the body's immune system or to target the tumor cells with antibody conjugates of various cytotoxic or chemotherapeutic agents. In practice, however, tumors in vivo have generally not been found to be very immunogenic and in many instances appear to be capable of evading the body's immune response. Today a great deal of anti-cancer work is directed at finding ways of increasing the immunogenicity of a tumor cell in vivo. For example, U.S. Pat. No. 6,120,763 (Fakhrai et al.) describes a method of preventing or reducing the severity of a
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cancer in a subject by stimulating the subject's immune response against the cancer. Many studies have attempted use of IgG as passive immunity or stimulation of natural IgG production to restrict tumor growth. As of today, there are no known vaccines for breast cancer, prostate cancer, or any other forms of mucosal cancers (Smyth M J et al. (2001) Nature Immunol 2, 293-299). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cosmetic composition containing a steroid and a 2-alkylalkanol or an ester thereof Inventor(s): Dreher, Susanne; (Paris, FR), Baldo, Francine; (Sceaux, FR) Correspondence: OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20010044430 Date filed: April 10, 2001 Abstract: A composition including at least one steroid chosen from DHEA and/or a biological precursor and/or a chemical or metabolic derivative of the latter, characterized in that it additionally comprises at least one 2-alkylalkanol comprising from 12 to 36 carbon atoms or an ester of such an alcohol. The invention also relates to the cosmetic and dermatological uses of this composition, in particular for preventing or treating chronological or actinic ageing and canities. Excerpt(s): The present invention relates to a composition including at least one steroid chosen from DHEA and/or a biological precursor and/or a chemical or metabolic derivative of the latter and at least one 2-alkylalkanol comprising from 12 to 36 carbon atoms or an ester of such an alcohol, to uses of the composition and to a process for dissolving the abovementioned steroid by means of at least one 2-alkylalkanol comprising from 12 to 36 carbon atoms or an ester of such an alcohol. DHEA or dehydroepiandrosterone is a natural steroid produced essentially by the corticoadrenal glands. Exogenous DHEA, administered topically or orally, is known for its ability to promote keratinization of the epidermis (JP-07 196 467) and to treat dry skin by increasing the endogenous production and the secretion of sebum and by thus strengthening the barrier effect of the skin (U.S. Pat. No. 4,496,556). DHEA is also described for the treatment of the symptoms of the menopause (U.S. Pat. No. 5,854,671) and in the prevention and treatment of osteoporosis (U.S. Pat. No. 5,776,923). The use of DHEA has also been suggested in the treatment of obesity and diabetes (WO 97/13500) or of cardiovascular diseases (U.S. Pat. No. 5,854,671) and in the treatment of some cancers, such as ovarian cancer (U.S. Pat. No. 5,798,347), uterine cancer (U.S. Pat. No. 5,872,114) or breast cancer (U.S. Pat. No. 5,824,671). In point of fact, DHEA only dissolves with difficulty in aqueous and aqueous/alcoholic media, which limits its formulation in cosmetic or dermatological compositions applied topically or orally. It thus has a tendency to recrystallize or to decompose. The result of this is a loss in effectiveness of these compositions to a greater or lesser extent, depending upon the degree of recrystallization and/or of decomposition, which goes against the desired objective. In addition, this recrystallization or decomposition can modify the overall stability of these compositions and their appearance, which can dissuade the consumer from using them. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Gene family encoding membrane steroid receptors Inventor(s): Zhu, Yong; (Greenville, NC), Thomas, Peter; (Portland, TX) Correspondence: Sanford E. Warren, Jr. GARDERE WYNNE SEWELL LLP; Suite 3000; 1601 Elm Street; Dallas; TX; 75201; US Patent Application Number: 20030170791 Date filed: June 11, 2002 Abstract: A family of genes that encode membrane steroid receptors is identified in mammals and fish. A putative progestin membrane receptor (mPR) from a fish ovary was cloned, expressed and characterized. Database searching with the fish ovary mPR lead to the discovery of a new family of steroid membrane receptor genes with highly conserved sequences and structures similar to fish mPR in human, mouse and swine tissues. The cDNA sequence for each of these mammalian genes was determined. The cDNAs appear to be members of a novel gene family, not closely related to any previously characterized vertebrate genes. Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/297,726, filed on Jan. 12, 2001. The present invention relates to membrane steroid receptors and, in particular, to a family of genes encoding membrane steroid receptors. The research carried out in the subject application was supported in part by grants from the National Science Foundation (NSF Number IBN-9980353) titled CLONING SEQUENCING AND EXPRESSION OF A STEROID MEMBRANE RECEPTOR. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Halogenated sulphamate-, phosphonate-, thiophosphonate-, sulphonamide- compounds as inhibitors of steroid sulphatase
sulphonate-
and
Inventor(s): Purohit, Atul; (Sterix Limited, GB), Reed, Michael John; (Sterix Limited, GB), Lloyd Potter, Barry Victor; (Sterix Limited, GB), Hejaz, Hatem; (Dubai, AE) Correspondence: FROMMER LAWRENCE & HAUG; 745 FIFTH AVENUE- 10TH FL. NEW YORK; NY; 10151; US Patent Application Number: 20030134829 Date filed: June 7, 2002 Abstract: A compound is described. The compound has the formula (Ia) as presented in the FIG. 1; wherein: X is a ring having at least 4 atoms in the ring; K is hydrocarbyl group; Rh1 is an optional halo group; Rh2 is an optional halo group; at least one of Rh1 and Rh2 is present; Rs is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group. The compound is capable of inhibiting steroid sulphatase (STS) activity. Excerpt(s): The present invention relates to a compound. In particular the present invention relates to a compound and to a pharmaceutical composition comprising the compound. The present invention also relates to the use of the compound or composition in therapy applications. Evidence suggests that oestrogens are the major mitogens involved in promoting the growth of tumours in endocrine-dependent tissues, such as the breast and endometrium. Although plasma oestrogen concentrations are similar in women with or without breast cancer, breast tumour oestrone and oestradiol levels are significantly higher than in normal breast tissue or blood. In situ synthesis of oestrogen is thought to make an important contribution to the high levels of oestrogens
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in tumours and therefore inhibitors, in particular specific inhibitors, of oestrogen biosynthesis are of potential value for the treatment of endocrine-dependent tumours. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immune modulation method using steroid compounds Inventor(s): Heggie, William; (Palmela, PT), Frincke, James M. (San Diego, CA), dos Anjos de Carvalho, Luis Daniel; (Paio Pires, PT), Prendergast, Patrick T. (County Kildare, IE), Thadikonda, Krupakar Paul; (Gaithersburg, MD), Vernon, Russell N. (Oak Hills, CA), Reading, Christopher L. (San Diego, CA), Ahlem, Clarence N. (San Diego, CA) Correspondence: HOLLIS-EDEN PHARMACEUTICALS, INC. 4435 EASTGATE MALL; SUITE 400; SAN DIEGO; CA; 92121; US Patent Application Number: 20030060425 Date filed: March 29, 2001 Abstract: The invention provides compositions comprising formula 1 steroids, e.g., 16.alpha.-bromo-3.beta.-hydroxy-5.alpha.-androstan-17-one hemihydrate and one or more excipients, including compositions that comprise a liquid formulation comprising less than about 3% v/v water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16.alpha.-bromo-3.beta.-hydroxy5.alpha.-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using the compounds. The invention also provides methods to make and use these immunomodulatory compositions and formulations. Excerpt(s): This application is a continuation-in-part of: (1) pending U.S. application Ser. No. 09/449,184, filed Nov. 24, 1999, which claims priority to abandoned U.S. provisional application Ser. No. 60/109,924, filed Nov. 24, 1998, and (2) pending U.S. application Ser. No. 09/414,905, filed Oct. 8, 1999, which claims priority to abandoned U.S. provisional application Ser. No. 60/140,028, filed Jun. 16, 1999 and (3) pending U.S. application Ser. No. 09/449,004, filed Nov. 24, 1999, which claims priority to abandoned U.S. provisional application Ser. No. 60/109,923, filed Nov. 24, 1998, and (4) pending U.S. application Ser. No. 09/535,675, filed Mar. 23, 2000, which claims priority to abandoned U.S. provisional application Ser. No. 60/126,056, filed Mar. 23, 1999, and abandoned U.S. provisional application Ser. No. 60/124,087, filed Mar. 11, 1999 and (5) pending U.S. application Ser. No. 09/449,042, filed Nov. 24, 1999, which claims priority to abandoned U.S. provisional application Ser. No. 60/110,127, filed Nov. 27, 1998, and (6) pending U.S. application Ser. No. 09/675,470, filed Sep. 28, 2000, which claims priority to abandoned U.S. provisional application Ser. No. 60/161,453, filed Oct. 25, 1999, and (7) pending U.S. application Ser. No. 09/586,673, filed Jun. 1, 2000, which claims priority to abandoned U.S. provisional application Ser. No. 60/145,823, filed Jul. 27, 1999, and (8) pending U.S. application Ser. No. 09/586,672, filed Jun. 1, 2000, which claims priority to abandoned U.S. provisional application Ser. No. 60/137,745, filed Jun. 3, 1999, and (9) pending U.S. application Ser. No. 09/461,026, filed Dec. 15, 1999, which claims priority to abandoned U.S. provisional application Ser. No. 60/112,206, filed Dec. 15, 1998, all of which are incorporated herein by reference in their entireties. The invention relates to methods to make and use steroids, such as 16.alpha.-bromo-3.beta.hydroxy-5.alpha.-androstane-17-one (16.alpha.-bromoepiandrosterone or hereafter
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"BrEA") and new analogs thereof. The steroids are useful for a number of therapeutic and non-therapeutic applications, including their use as immune modulators in conditions such as infections or inflammation. The present invention also relates to methods to make the compounds, compositions and formulations. The invention also provides methods and compositions to prevent or treat a hematopoietic disorder such as thrombocytopenia or neutropenia by administering to a subject a steroid such as 3,7,16,17-tetrahydroxy-andro- st-5-ene, 3,16,17-trihydroxyandrostane, 3-hydroxy-16haloandrostane-17-one or 3,17-dihydroxy-16-haloandrostane, which is optionally combined with an agent that enhances monocyte or neutrophil activity. BrEA and its preparation from the steroid compound 3.beta.-hydroxyandrost-5-en-17-one (dehydroepiandrosterone or DHEA) have been described (see, e.g., J. Org. Chem. 1962 27:2937-2938). Methods to prepare DHEA and other steroids and their biological properties have been described, see, e.g., U.S. Pat. Nos. 2,833,793, 2,911,418, 3,148,198, 3,471,480, 3,976,691, 4,268,441, 4,427,649, 4,542,129, 4,666,898, 4,956,355, 5,001,119, 5,043,165, 5,077,284, 5,028,631, 5,110,810, 5,157,031, 5,162,198, 5,175,154, 5,277,907, 5,292,730, 5,296,481, 5,372,996, 5,387,583, 5,407,684, 5,424,463, 5,461,042, 5,478,566, 5,506,223, 5,518,725, 5,527,788, 5,527,789, 5,532,230, 5,559,107, 5,562,910, 5,583,126, 5,585,371, 5,587,369, 5,591,736, 5,593,981, 5,610,150, 5,635,496, 5,641,766, 5,641,768, 5,656,621, 5,660,835, 5,686,438, 5,696,106, 5,700,793, 5,707,983, 5,709,878, 5,710,143, 5,714,481, 5,728,688, 5,736,537, 5,744,462, 5,753,237, 5,756,482, 5,776,921, 5,776,923, 5,780,460, 5,795,880, 5,798,347, 5,798,348, 5,804,576, 5,807,848, 5,807,849, 5,811,418, 5,824,313, 5,824,668, 5,824,671, 5,827,841, 5,837,269, 5,837,700, 5,843,932, 5,846,963, 5,859,000, 5,872,114 and 5,872,147; German patent numbers 2035738 and 2705917; PCT publication numbers WO 95/21617, WO 97/48367, WO 98/05338, WO 98/50040, WO 98/50041, WO 98/58650; European publication number 0020029; Ben-David, et al., Proc. Soc. Expt. Biol. Med. 1967 125:1136-1140, Coleman et al., Diabetes 1982 31:830, Oertel, et al., J. Steroid Biochem. 1972 3:493-493, Pashko, et al., Carcinogenesis 1981 2:717-721, Schwartz et al., Nutr. Cancer 1981 3:46-53; Dyner et al., J. Acquired Immune Deficiency Syndromes 1993 6:459-465; A. A. Afanasii and Y. A. Titov, Total Steroid Synthesis, Plenum Press, New York, 1970, see, e.g., p 1-304. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Membrane receptors for steroids and sterols Inventor(s): Weiss, Bertram; (Berlin, DE), Toschi, Luisella; (Berlin, DE), Lessl, Monika; (Berlin, DE) Correspondence: MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BLVD. SUITE 1400; ARLINGTON; VA; 22201; US Patent Application Number: 20030045699 Date filed: April 26, 2002 Abstract: Four splice variants of a membrane receptor for steroids and sterols and their use are described. Excerpt(s): The invention relates to nucleic acids that code for a membrane receptor for steroids and sterols, polypeptides and their use. According to the standard model of steroid hormone action, the steroids bind to intracellular receptors that as ligandactivated transcription factors regulate the gene expression. It is common to refer to the direct action of the steroid hormones via their nuclear-position receptors to the transcription of target genes as genomic effects. Genomic effects are characterized by their time-delayed entry, i.e., more than 5 minutes up to several hours after hormone
Patents 417
administration (McEwen et al. 1978 in: Reichlin et al. Eds., The Hypothalamus, Raven Press, p. 255 ff). In contrast to the genomic actions, "quick" non-genomic effects that occur within a few seconds or minutes after the administration of steroid hormones and whose cause cannot lie in regulation of transcription have been observed for many years. Biochemical indicators for these effects are changes of membrane potential and/or the influencing of ion channels in the cell membrane (Watson et al. 1999, Proc Soc Exp Biol Med 220, 9 ff). These effects could be mediated by membrane-fixed receptors. Steroid effects that indicate the existence of a membrane receptor can also often be triggered by steroid derivatives that can no longer go through the plasma membrane by coupling to a bulky carrier molecule (for example serum albumin) and, made visible by fluorescence microscopy, bind to the cell surface. These results, just like binding studies with cell membranes and immune staining, indicate the existence of a membrane-fixed steroid receptor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for synthesizing 5beta, 6beta-epoxides of steroids by a highly beta-selective epoxidation of delta5-unsaturated steroids catalyzed by ketones Inventor(s): Jiao, Guan-Sheng; (College Station, TX), Yang, Dan; (Hong Kong, HK) Correspondence: Sandra B. Weiss; Jones, Day, Reavis & Pogue; 77 West Wacker; Chicago; IL; 60601; US Patent Application Number: 20030018188 Date filed: March 6, 2002 Abstract: A general, efficient, and environmentally friendly method is provided for producing mostly.beta.-epoxides of.DELTA.sup.5-unsaturated steroids using certain ketones as the catalyst along with an oxidizing agent, or by using certain dioxiranes. In another aspect of the invention, a method is provided for producing mostly 5.beta.,6.beta.-epoxides of steroids from.DELTA.sup.5-unsaturated steroids having a substituent at the 3.alpha.-position by an epoxidation reaction using a ketone along with an oxidizing agent under conditions effective to generate epoxides, or using a dioxirane under conditions effective to generate epoxides. A whole range of.DELTA.sup.5unsaturated steroids, bearing different functional groups such as hydroxy, carbonyl, acetyl or ketal group as well as different side chains, were conveniently converted to the corresponding synthetically and biologically interesting 5.beta.,6.beta.-epoxides with excellent.beta.-selectivities and high yields. Excerpt(s): This application is a continuation-in-part of non-provisional application Ser. No. 09/788,201 filed Feb. 16, 2001, which claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Application Serial No. 60/183,396 filed Feb. 18, 2000. The present invention is directed to the field of synthesizing epoxides of steroids. Steroid epoxides are an important class of oxysterols (oxygenated derivatives of cholesterol) involved in the regulation of cell proliferation and cholesterol homeostasis. They are versatile intermediates for steroid synthesis and useful probes for biochemical studies of enzymes. Steroid epoxides are also useful intermediates for the preparation of other oxysterols. For example,.alpha.- and.beta.-epoxides of cholesterol are auto-oxidation products of cholesterol in vivo, and both are cytotoxic and mutagenic. The isomeric.alpha.- and.beta.-epoxides are hydrolysed by cholesterol 5,6-epoxide hydrolase to cholestane-3.beta.,5.alpha.,6.beta.-triol which has potent hypocholesterolemic activity. On the other hand, both epoxides inhibit the cholesterol 7.alpha.-hydroxylase which catalyzes the rate-determining step of bile acid synthesis. As 5.alpha.,6.alpha.-epoxides
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are readily available via epoxidation of.DELTA.sup.5-unsaturated steroids with peracids, there have been extensive studies on the biological actions of those epoxides and their derivatives. In contrast, much less is known about the 5.beta.,6.beta.-epoxides and their derivatives because they are difficult to obtain in high selectivity. More importantly, the 5.beta.,6.beta.-epoxy functionality is found in a number of naturally occurring steroids of antitumor activities, e.g., jaborosalactone A, withaferin A, and withanolide D. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of increasing testosterone and related steroid concentrations in women Inventor(s): Dudley, Robert E. (Kenilworth, IL) Correspondence: Thomas R. Stiebel, Jr. Mayer, Brown, Rowe & Maw; P.O. Box 2828; Chicago; IL; 60690; US Patent Application Number: 20030022877 Date filed: May 21, 2002 Abstract: The present invention relates to methods, kits, combinations, and compositions for treating, preventing or reducing the risk of developing a testosterone deficient disorder, or the symptoms associated with, or related to a testosterone deficient disorder in a subject in need thereof. The present invention also relates to a method of administering a steroid in the testosterone synthetic pathway to a subject in need thereof. In addition, the methods, kits, combinations and compositions may be used in conjunction with other pharmaceutical agents effective at treating, preventing, or reducing the risk of developing a testosterone deficient disorder. The present invention also can also be used in conjunction with a pharmacologically effective amount of an estrogenic hormone. Furthermore, the methods, kits, combinations and compositions can be used in conjunction with a pharmacologically effective amount of another steroid or pharmaceutical agent that increases serum testosterone levels in a mammal. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/292,398, filed May 21, 2001, which is hereby incorporated by reference. The present invention is related to methods, kits, combinations, and compositions for transdermally delivering an effective amount of testosterone to a subject in need thereof. Transdermal preparations of testosterone have provided a useful delivery system for normalizing serum testosterone levels in hypogonadal men and preventing the clinical symptoms and long term effects of androgen deficient men. Available transdermal preparations of testosterone include, for example, TESTODERM.RTM., TESTODERM.RTM. TTS, and ANDRODERM.RTM. Testosterone is also available in other formulations including those available as an injectable, for example, DEPO-TESTOSTERONE.RTM. (testosterone cypionate), and DELATESTRYL BTG.RTM. (testosterone enanthate), or as a gel, for example, ANDROGEL.RTM. marketed by Unimed Pharmaceuticals, Inc., Deerfield, Ill., the assignee of this application. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 419
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Method of producing steroid derivatives Inventor(s): Yano, Shingo; (Saitama, JP), Yamagami, Ryutaro; (Saitama, JP), Nozaki, Kenji; (Saitama, JP), Asao, Tetsuji; (Saitama, JP) Correspondence: OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20020143199 Date filed: October 18, 2001 Abstract: A method of producing 3-alkoxy-1,3,5(10)-triene-6-one-steroid derivatives having, in the steroid skeleton thereof, a partial structure of A- and B-rings represented by formula (2): 1(wherein R represents an alkyl group, a cycloalkyl group, an alkenyl group, or an aralkyl group), including reacting a 19-norsteroid derivative having, in the steroid skeleton thereof, a partial structure of A- and B-rings represented by formula (1): 2with an alcohol represented by ROH (wherein R has the same meaning as defined above) and iodine in the absence of a rare earth compound catalyst. According to the method of the present invention, 3-alkoxy-1,3,5(10)-triene-6-one-steroids can be selectively produced from 19-norsteroides through a single reaction step without employment of a special catalyst. Excerpt(s): The present invention relates to a method of selectively producing 3-alkoxy1,3,5(10)-triene-6-one-steroid derivatives, which are useful for drugs and diagnostic agents. by the reaction, in methanol, of 19-nor-4-androstene-3,17-dione with iodine in the presence of ceric ammonium nitrate as a rare earth compound catalyst, to thereby yield estrone-methyl ether (predominant product) and oxoestrone-methyl ether (byproduct) in the form of a mixture. However, this method is not industrially efficient, since it involves a reaction employing a rare earth metal compound catalyst which requires burdensome waste treatment; the yield of 6-one species is as low as 23-27%; and high-cost silica gel column chromatography must be carried out so as to separate from by-product and purify the target compound. As stated above, the conventional technique is not preferred as a method for industrially producing 3-alkoxytriene-6-one steroids from 19-norsteroids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of using a cyclooxygenase-2 inhibitor and sex steroids as a combination therapy for the treatment and prevention of dysmenorrhea Inventor(s): Krasnow, Joel; (Peapack, NJ) Correspondence: Pharmacia Corporation; Corporate Patent Department; 800 North Lindbergh Blvd. Mail Zone O4E; St. Louis; MO; 63167; US Patent Application Number: 20030008870 Date filed: February 4, 2002 Abstract: The present invention provides methods for the treatment and prevention of dysmenorrhea in a woman using a combination of a cyclooxygenase-2 inhibitor and sex steroids. Excerpt(s): The present invention relates to methods for the treatment and prevention of dysmenorrhea in a woman using a combination of a cyclooxygenase-2 inhibitor and sex steroids. In women, the menstrual cycle involves a complex series of hormonal changes. A consequence of these hormonal changes is the growth of the uterine lining (referred to
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as the endometrium). In the absence of pregnancy, the endometrium is shed in a process called menstruation. This process involves the release of prostaglandins, which cause contractions of the smooth muscle in the uterus. In some women, these contractions cause substantial pain, dysmenorrhea, which interferes with their daily activities. The time at which menstruation occurs varies in that it can not be predicted with certainty in any one woman. The variability in the onset of menstrual cycles is dependent upon many variables including the individual woman, her age and underlying medical and psychosocial conditions. This makes it difficult to predict the onset of menses. Nonsteroidal anti-inflammatory agents (NSAIDs) that inhibit prostaglandin synthesis are effective in reducing dysmenorrhea (Lundstrom, V., et al. Acta Obstet. Gynecol. Scand. Suppl., 113, 83-85 (1983)). They are most effective when administered prior to the onset of menstrual pain by 24-48 hours. Since predicting the precise timing of menstruation is difficult, attempts to maximize efficacy by initiating treatment prior to menses may result in several days of unnecessary medication. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and labeled molecules for determining ligand binding to steroid receptors Inventor(s): Wasti, Ruby C. (Bethel, CT), Nabozny, Gerald H. (New Milford, CT), Goldrick, Susan E. (Danbury, CT), Thomson, David S. (Ridgefield, CT), Crute, James J. (San Diego, CA), Proudfoot, John R. (Newtown, CT), Nelson, Richard M. (Newtown, CT) Correspondence: BOEHRINGER INGELHEIM CORPORATION; 900 RIDGEBURY ROAD; P O BOX 368; RIDGEFIELD; CT; 06877; US Patent Application Number: 20030017503 Date filed: May 20, 2002 Abstract: The invention relates to fluorescence polarization (FP) methods for detecting and evaluating ligand binding to steroid receptors which are associated with heat shock proteins (hsps). The invention also relates to novel labeled molecules, in particular, fluorescence probes, which are useful in the methods of the invention. Excerpt(s): This application claims priority benefit to U.S. Provisional Application serial No. 60/291,877 filed May 18, 2001. The invention relates to fluorescence polarization (FP) methods for detecting and evaluating ligand binding to steroid receptors which are associated with heat shock proteins (hsps). The invention also relates to novel fluorescence probes which are useful in the methods of the invention. Steroids and related hormones play an important role in regulating development, differentiation and homeostasis. There are five major classes of steroid hormones: progestins, glucocorticoids, mineralocorticoids, androgens and estrogens. The hormones exert their regulatory effects by binding to a superfamily of intracellular receptors, which are direct modulators of gene transcription. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 421
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Methods for determining steroid responsiveness Inventor(s): Whitehead, Alexander Steven; (Wayne, PA) Correspondence: TESTA, HURWITZ & THIBEAULT, LLP; HIGH STREET TOWER; 125 HIGH STREET; BOSTON; MA; 02110; US Patent Application Number: 20030138781 Date filed: January 22, 2002 Abstract: The invention provides a diagnostics assay for measuring the responsiveness to a drug by comparing the mRNA levels of a gene that responds to the drug, such as a steroid, to the mRNA levels of a gene that does not respond to the drug. Methods according to the invention are useful for predicting the ability of a patient (or a tissue, body fluid or cell sample in vitro) to respond to a drug or steroid at any stage of their treatment (i.e., before, during or after), and to monitor the patient (or a tissue, body fluid or cell) over time to assess continued responsiveness to the drug or steroid. Excerpt(s): The invention relates to a diagnostic assay for steroid responsiveness. Many diseases (e.g., rheumatoid arthritis, inflammatory bowel diseases, systemic lupus erythematosis, asthma) that are primarily inflammatory, or that have a major inflammatory component, are treated with steroids such as prednisone. In addition, some cancers are treated with steroids, as are transplant recipients, to avoid transplant rejection. However, the effectiveness of steroids varies from patient to patient and is usually impossible to predict. Some patients may be constitutively non-responsive to a particular medication, and others may become refractory to treatment over time. In some cases, patients may experience symptomatic relief, but attempts to withdraw therapy lead to disease flare. As a consequence, the inclination for doctors to continue steroid therapy and even to increase the dosage of a steroid is associated with serious, cumulatively debilitating, side effects. The clinical screening of patients who are candidates for steroid therapy for their ability to respond to steroids and the monitoring of patients who are undergoing steroid therapy but who may be transitioning from steroid responder to non-responder (i.e., refractory) status is therefore of significant clinical importance. A need therefore exists for a diagnostic assay or test for steroid responsiveness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for screening or monitoring the risk of cardiovascular disease relating to sex steroid compound or composition intake and methods for screening sex steroid compound Inventor(s): Emeis, Josephus Jan; (Boskoop, NL), Kluft, Cornelis; (Sassenheim, NL) Correspondence: NIXON & VANDERHYE P.C. 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20020110523 Date filed: November 5, 2001 Abstract: A method for screening for negative side effects of a sex steroid compound or composition in a subject, by carrying out an assay on the subject or on a sample derived from the subject determining whether an increase of the compound or composition on the level of an acute phase reactant or a metabolic derivative thereof has occurred since applying the compound or composition to the subject, the acute phase reactant being
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selected from the group consisting of positive Acute Phase Reactants (ARPs) with the exclusion of ceruloplasmin and coagulation/thrombosis associated factors. An increase in the level of the acute phase reactant being indicative of negative side effects. A sex steroid compound or composition characterized by a lower increase in APR level than a third generation oral contraceptive, as determined in a manner according to the invention is also provided; the compound or composition not being a second generation oral contraceptive. Excerpt(s): Preparations with sex steroids have been developed for birth control, supplementation e.g. when women enter the menopause, replacement when women have had hysterectomies. Alternatively they are used for sex-change processes and growth inhibition for tall boys and girls. The preparations used in the field of anticonception have in recent history been adapted with regard to both dosage and type of compounds. The reason was the recognition that besides the targeted action of the sex steroids in anticonception, additional effects occurred in the first generation pills and increased occurrence of cardiovascular disease in these groups was documented in epidemiological surveys. The dose of the estrogenic component was identified as an important determinant and was reduced gradually with time. Up till recently, epidemiology supported these adaptations of the third generation in showing reductions in cardiovascular side affects. Newer formulations with lower dosages are being evaluated for future use. Up till recently, epidemiology supported these adaptations in showing reductions in cardiovascular side effects. Epidemiological studies are preceeded by studies on intermediary end-points or beacons to document before introduction of a new formulation with the promise of reduced side effects. Evaluations of intermediary end-points for cardiovascular disease have focussed on metabolic changes in lipid, carbohydrate and haemostatic processes. In more recent years their usually separate evaluation was more integrated as advocated by the consensus development meeting on this topic in Esbjerg, Denmark held from May 18-20 in 1989. The said consensus also concluded that the metabolic changes followed the trend of being smaller with newer pills, and that the objective to be achieved in future is a minimal change or even more desirably absence of any change in metabolism. The consensus also stated "The metabolic alterations induced by progestagen-only pills were not considered extensively because current evidence suggested that changes are small even by sensitive indicators of lipid and carbohydrate metabolism and components of hemostasis. Furthermore there are insufficient epidemiologic data to determine whether the progestagen-only pills influence the risk of cardiovascular diseases." They further state that the progestagen component is mainly responsible for the effect of OCs (oral contraceptives) on carbohydrate metabolism and that the effects on hemostasis are conceivably estrogen mediated because they have not been demonstrated in progestagen-only preparations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of dissociating nongenotropic from genotropic activity of steroid receptors Inventor(s): Manolagas, Stavros C. (Little Rock, AR), Kousteni, Stavroula; (Little Rock, AR) Correspondence: KING & SPALDING; 191 PEACHTREE STREET, N.E. ATLANTA; GA; 30303-1763; US Patent Application Number: 20020137209 Date filed: June 13, 2001
Patents 423
Abstract: This invention concerns the fundamental discovery of the understanding of the mechanism of action of steroidal nongenotropic effects and their relation to steroidal genotropic effects. It has been discovered that (i) steroidal nongenotropic effects and genotropic effects can be mediated by the same steroid receptor; (ii) both effects are ligand-induced; (iii) the nongenotropic effect occurs due to a ligand-induced activation of the ligand binding domain, which can be fast and loose fitting; (iv) the genotropic effect occurs due to a ligand-induced activation of the DNA-binding domain of the steroid receptor, which is typically a result of a slower, stronger interaction; and (v) the nongenotropic effect of a ligand interaction can be dissociated from the genotropic effect of a ligand interaction, in such a manner to effect a selective response. This invention also describes, for the first time, that certain steroids are capable of inducing a nongenotropic effect via binding to an unrelated steroid receptor Excerpt(s): This invention is in the field of steroid signalling, and in particular describes a method of dissociating a steroidal nongenotropic effect from the steroidal genotropic effect, and a method for screening compounds that are capable of inducing a steroidal nongenotropic effect without substantially inducing a steroidal genotropic effect or are capable of inducing a steroidal genotropic effect without substantially inducing a steroidal nongenotropic effect. This invention also describes, for the first time, that certain steroids are capable of inducing a nongenotropic effect via binding to an unrelated steroid receptor. Due to similarities in molecular structure and homologies in protein sequence, a number of proteins have been classified into a superfamily of steroid nuclear receptors. The steroid protein receptor family includes at least sixty four known receptors (Cell, Vol 97, 161-163, Apr. 16, 1999), including the.alpha. and.beta. form of the estrogen receptors (ER.alpha. and ER.beta.), the estrogen receptor related receptor-1 and receptor-2 (ERR-1 and ERR-2), the androgen receptor (AR), the progesterone receptor (PR), the retinoic acid receptor (and related orphan receptors ROR-.alpha., ROR-.beta., and ROR-.gamma.); the glucocorticoid receptor (GR), the mineralcorticoid receptor (MR), the Vitamin D receptor, the neuroactive receptor, the famesoid X receptor (FXR), the liver X receptor (LXR.alpha. and LXR.beta.), the thyroid hormone receptors A and B (which bind triiodothyronine (T3) and thyroxine (T4)), the COUP-TF receptor, the ecdysone receptor, the peroxisome proliferator activated protein receptors (PPAR, including PPAR.alpha., PPAR.gamma., and PPAR.delta.), pregnane X (PXR), the bile acid binding family, as well as chimeric receptors and orphan receptors. It has traditionally been accepted that steroids bind to intracellular receptors and subsequently modulate transcription and protein synthesis typically via a steroid/receptor complex that induces gene activity. Even though the steroid receptors are primarily known as ligand-activated transcription factors, recently, a number of very rapid (e.g., seconds to approximately fifteen minutes) effects of steroids have been identified that are inconsistent with a genotropic effect by virtue of the rapidity of action. These observed nongenotropic effects of steroid hormones were recently reviewed by Falkenstein, et al., in "Multiple Actions of Steroid Hormones-A Focus on Rapid, Nongenotropic Effects," Pharmacol. Rev 52:513-555, 2000. See also McEwen, B. S. and Alves, S. E., Endocr. Rev. 20, 279-307, 1999. Many of these rapid actions have been attributed to the ability of estrogens or other steroids to interact with putative membrane-associated receptors (Watson, et al., Proc. Soc. Exp. Biol. Med., 220, 9-19, 1999). However, heretofor it was unknown whether these nongenotropic effects are mediated by proteins that are the same as or distinct from those that mediate the transcriptional effects of the steroids. Moreover, the relationship of nongenotropic effects of steroids to the transcriptional activity of the classical receptors is completely unknown. For example, Falkenstein et al. made the following observations in their 2000 review article. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Modified steroid hormones for gene therapy and methods for their use Inventor(s): O'Malley, Bert W. (Houston, TX), Tsai, Ming-Jer; (Houston, TX), Tsai, Sophia Y. (Houston, TX), Ledebur, Harry C. JR. (Spring, TX), Wang, Yaolin; (Iselin, NJ), Kittle, Joseph D. JR. (Houston, TX) Correspondence: LYON & LYON LLP; 633 WEST FIFTH STREET; SUITE 4700; LOS ANGELES; CA; 90071; US Patent Application Number: 20020147327 Date filed: July 25, 2001 Abstract: The present invention provides modified proteins of steroid hormone receptors. These mutated proteins are useful as gene medicines. In particular, these mutated proteins are useful for regulating expression of genes in gene therapy. In addition, the present invention provides plasmids encoding for the desired mutated steroid hormone receptor proteins, as well as cells transfected with those plasmids. Excerpt(s): This application relates to U.S. patent application Ser. No. 60/029,964, filed Oct. 29, 1996, entitled "MODIFIED STEROID HORMONES FOR GENE THERAPY AND METHODS FOR THEIR USE" by O'Malley et al. (Lyon & Lyon Docket No. 222/085) which is incorporated herein by reference in its entirety, including any drawings. This application is also related to copending U.S. application Ser. No. 08/479,913, O'Malley et al., filed Jun. 7, 1995, entitled "Modified Steroid Hormones for Gene Therapy and Methods for Their Use," which is a continuation-in-part of co-pending U.S. application Ser. No. 07/939,246, Vegeto, et al., filed Sep. 2, 1992, entitled "Mutated Steroid Hormone Receptors, Methods for Their Use and Molecular Switch for Gene Therapy," the whole of which (including drawings) are all hereby incorporated by reference in their entirety. In addition, this application is related to U.S. Pat. No. 5,364,791, Vegeto, et al., issued Nov. 15, 1994, entitled "Progesterone Receptor Having C-Terminal Hormone Binding Domain Truncations," and PCT/US93/04399 the whole of which (including drawings) are both hereby incorporated by reference in their entirety. This invention relates to gene therapy, whereby modified steroid receptors regulate the expression of genes within tissue. In particular, the modified steroid receptors contain a DNA binding domain, one or more transregulatory domains, and a ligand binding domain and are capable of binding a non-natural ligand. The following description of the background of the invention is provided to aid in the understanding of the invention but is not admitted to describe or constitute prior art to the invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Mutated steroid hormone receptors, methods for their use and molecular switch for gene therapy Inventor(s): O'Malley, Bert W. (Houston, TX), Kittle, Joseph D. JR. (Houston, TX), Ledebur, Harry C. JR. (Spring, TX), Tsai, Ming-Jer; (Houston, TX), Tsai, Sophia Y. (Houston, TX), Wang, Yaolin; (Iselin, NJ) Correspondence: PERKINS COIE LLP; WO; POST OFFICE BOX 1208; SEATTLE; WA; 98111-1208; US Patent Application Number: 20030109683 Date filed: April 16, 2002
Patents 425
Abstract: The present invention provides mutant proteins of steroid hormone receptors. These mutant proteins are useful in methods of distinguishing a steroid hormone receptor antagonist from a steroid hormone receptor agonist. The present invention also provides plasmids containing mutated steroid hormone receptor proteins and cells transfected with those plasmids. In addition, the present invention provides methods for determining whether a compound is a steroid hormone receptor antagonist or agonist. Also, the present invention provides methods of determining endogenous ligands for steroid hormone receptors. The invention further provides a molecular switch protein for regulating expression in gene therapy. Excerpt(s): The present application claims priority to the filing dates of each of the above-identified applications which are hereby incorporated by reference (including drawings) as if fully set forth herein. The present invention relates generally to the fields of molecular endocrinology and receptor pharmacology. It further relates to molecular switches for gene therapy. More specifically, the present invention relates to a novel in vivo method for the identification of steroid hormone receptor agonists and antagonists and to a molecular switch involving a modified steroid receptor for up-regulating and down-regulating the synthesis of heterologous nucleic acid sequences which have been inserted into cells. This invention has applicability to gene therapy, whereby modified steroid receptors regulate the expression of genes within tissue. In particular, the modified steroid receptors contain a DNA binding domain, one or more transregulatory domains, and a ligand binding domain and are capable of binding a non-natural ligand. Steroid receptors are responsible for the regulation of complex cellular events, including transcription. The ovarian hormones, estrogen and progesterone, are responsible, in part, for the regulation of the complex cellular events associated with differentiation, growth and functioning of female reproductive tissues. These hormones play also important roles in development and progression of malignancies of the reproductive endocrine system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel steroid hormone receptor interacting protein kinase Inventor(s): Balk, Steven; (Needham, MA) Correspondence: CLARK & ELBING LLP; 101 FEDERAL STREET; BOSTON; MA; 02110; US Patent Application Number: 20030166623 Date filed: January 19, 2001 Abstract: The present invention features a novel p21-activated kinase that interacts with steroid hormone receptors, the steroid hormone receptor interacting p21-activated kinase (PAK.sub.SI). In general, the invention provides methods of inhibiting hormone related cancers. More particularly, the present invention relates to inhibiting prostate cancer and breast cancer. The present invention further provides methods of activating the therapeutic effects of steroid hormone receptors, particularly the estrogen receptor. Alternatively, the present invention provides methods of diagnosing steroid hormone receptor-related diseases. Excerpt(s): This application claims benefit from U.S. Provisional Application No. 60/176,859, filed Jan. 19, 2000, incorporated herein by reference. Prostate cancer now ranks as the most prevalent cancer in men. Approximately 160,000 new cases are diagnosed each year; of these new cases, 35,000 will die of metastatic disease. In women,
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breast cancer kills 45,000 women per year. Steroid hormone receptors and the factors that bind steroid hormone receptors are key players in the maintenance of healthy tissue. Similarly, disregulation of steroid hormone receptors and steroid hormone receptor interacting proteins are important to the development of a wide variety of sex steroid hormone dependent cancers and diseases. Current therapies for such afflictions include surgery (e.g., castration) and chemical treatment (e.g., chemotherapy and hormone ablation therapy). Androgens in normal prostate epithelium appear to primarily drive differentiation. In contrast, prostate cancer growth is directly androgen stimulated. Thus, one common therapy for the treatment of prostate cancer is androgen ablation therapy, to which most patients respond. Unfortunately, virtually all prostate cancer relapse is clinically androgen independent. Significantly, most androgen independent tumors express high levels of androgen receptor as well as androgen receptor regulated genes, indicating that the androgen receptor is transcriptionally active (van der Kwastet et al., Int. J. Cancer 48, 189-193 (1991); Ruizeveld de Winter et al., Am. J. Pathol. 144, 735-746 (1994); Taplin et al., N. Engl. J. Med. 332, 1393-1398 (1995); Hobisch et al., Cancer Res. 55, 3068-3072 (1995); Visakorpi et al., Nat. Genet. 9, 401-406 (1995); and Koivisto et al., Cancer Res. 57, 314-319 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
NOVEL STEROID-ACTIVATED NUCLEAR RECEPTORS AND USES THEREFOR Inventor(s): BLUMBERG, BRUCE; (SAN DIEGO, CA), EVANS, RONALD M. (LA JOLLA, CA) Correspondence: Stephen E. Reiter; foley & Lardner; 402 W. Broadway; 23rd floor; San Diego; CA; 92101; US Patent Application Number: 20030064430 Date filed: January 9, 1998 Abstract: In accordance with the present invention, there is provided an example of a novel class of nuclear receptor(s), termed the steroid X receptor (SXR). SXR is expressed almost exclusively in the liver, the primary site of xenobiotic and steroid catabolism. Unlike classical steroid receptors, SXR heterodimerizes with RXR and binds to directly repeated sequences related to the half-site, AGTTCA. SXR can activate transcription through response elements found in some steroid inducible P450 genes in response to a wide variety of natural and synthetic steroid hormones, including antagonists such as PCN--ideal properties for a "steroid sensing receptor" which mediates the physiological effect(s) of hormones. SXR represents the first new class of steroid receptors described since the identification of the mineralocorticoid receptor ten years ago. Also provided according to the invention are nucleic acid sequences encoding the above-identified receptors, as well as constructs and cells containing same, and probes derived therefrom. Furthermore, it has also been discovered that a wide variety of substrates modulate the transcription activating effects of invention receptors. Excerpt(s): The present invention relates to intracellular receptors, nucleic acids encoding same, and uses therefor. In a particular aspect, the present invention relates to methods for the modulation of physiological response to elevated levels of steroids and steroid-like compounds. Nuclear receptors constitute a large superfamily of liganddependent and sequence-specific transcription factors. Members of this family influence transcription either directly, through specific binding to the promoters of target genes (see Evans, in Science 240:889-895 (1988)), or indirectly, via protein-protein interactions with other transcription factors (see, for example, Jonat et al., in Cell 62:1189-1204 (1990),
Patents 427
Schuele et al., in Cell 62:1217-1226 (1990), and Yang-Yen et al., in Cell 62:1205-1215 (1990)). The nuclear receptor superfamily (also known in the art as the "steroid/thyroid hormone receptor superfamily") includes receptors for a variety of hydrophobic ligands, including cortisol, aldosterone, estrogen, progesterone, testosterone, vitamin D.sub.3, thyroid hormone and retinoic acid, as well as a number of receptor-like molecules, termed "orphan receptors" for which the ligands remain unknown (see Evans, 1988, supra). These receptors all share a common structure indicative of divergence from an ancestral archetype. Lipophilic hormones such as steroids, retinoic acid, thyroid hormone, and vitamin D3 control broad aspects of animal growth, development and adult organ physiology. The effects of these hormones are mediated by members of the nuclear receptor superfamily. The nuclear receptors for such non-steroidal compounds as thyroid hormone (TR), vitamin D3 (VDR), all-trans retinoic acid (RAR), fatty acids and eicosanoids (PPAR) form heterodimers with the 9-cis retinoic acid receptor (RXR) that bind bipartite hormone-response elements (HREs) composed of directly repeated half sites related to the sequence AGGTCA (see, for example, Mangelsdorf and Evans in Cell 83:841 (1995)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Percutaneous absorption type steroid preparation for external use Inventor(s): Kokubo, Takemasa; (Tokyo, JP), Kanehira, Koichi; (Okayama, JP), Nakao, Ken-ichi; (Tokyo, JP), Furukawa, Yoshiko; (Tokyo, JP) Correspondence: DINSMORE & SHOHL, LLP; 1900 CHEMED CENTER; 255 EAST FIFTH STREET; CINCINNATI; OH; 45202; US Patent Application Number: 20030171343 Date filed: November 15, 2002 Abstract: A percutaneous absorption type steroid preparation for external use, wherein the preparation form of the preparation for external use is a patch that a pressuresensitive adhesive layer containing a steroidal antiphlogistic is provided on a support, and the pressure-sensitive adhesive layer further contains a dissolution aid for the steroidal antiphlogistic and an accelerator for percutaneous absorption. Excerpt(s): The present invention relates to a percutaneous absorption type steroid preparation for external use, and more particularly to a percutaneous absorption type steroid preparation for external use for percutaneously administering a steroidal antiphlogistic to a local tissue. Examples of commercially available percutaneous absorption type preparation for external use containing a nonsteroidal antiphlogistic include those of various preparation forms such as gel, ointment, cream, poultice and plaster. These percutaneous absorption type nonsteroid preparations for external use have physiological activity such as anti-inflammatory action, anti-allergic action and immunosuppressive action and exhibit a local anti-inflammatory effect, but can not exhibit a sufficient anti-inflammatory effect on a disease in a deep part of a vital tissue, such as rheumatoid arthritis, osteoarthritis or tendosynovitis. On the other hand, a steroidal antiphlogistic cannot exhibit an anti-inflammatory effect even when it is applied to a diseased part as a preparation for external use, such as an ointment because it does not deeply penetrate into the interior of the skin. For this reason, a disease in a deep part of a vital tissue, such as rheumatoid arthritis has heretofore been mainly treated by internal use and/or injection of a steroidal antiphlogistic. However, the internal use and injection of the steroidal antiphlogistic have involved a problem that the steroidal antiphlogistic itself has strong side effects.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Phosphoric acid isomerization of A 5 (10), 9 (11) - diene steroid to the corresponding 4, 9-diene steriod Inventor(s): Vaidyanathan, Rajappa; (Portage, MI) Correspondence: VAN DYKE, GARDNER, LINN AND BURKHART, LLP; 2851 CHARLEVOIX DRIVE, S.E. P.O. BOX 888695; GRAND RAPIDS; MI; 49588-8695; US Patent Application Number: 20030109728 Date filed: December 10, 2002 Abstract: The invention is a process for the preparation of a.DELTA.sup.4,9-steroid of formula (II) 1which comprises contacting a.DELTA.sup.5(10),9(11)-steroid of formula (I) 2with a phosphorous containing acid. Excerpt(s): This patent application claims priority of invention under 35 U.S.C.sctn.119(e) from U.S. provisional patent application Serial No. 60/339,620 filed Jan. 12, 1912. The present invention is a chemical process for the isomerization of the.DELTA.sup.5(10),9(11)-double bonds in a steroid to the corresponding.DELTA.sup.4,9-isomer. J. Am. Chem. Soc., 73, 4133 (1951) discloses isomerization of a.DELTA.sup.8(9)-12-one steroid to the corresponding.DELTA.sup.9(11)-12-one steroid using hydrochloric acid in methanol. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Polycaprolactone-b-poly (ethylene oxide) copolymer non-cross-linked micelles as a delivery vehicle for steroid Inventor(s): Allen, Christine; (Richmond, CA), Eisenberg, Adi; (Montreal, CA), Maysinger, Dusica; (Montreal, CA) Correspondence: SWABEY OGILVY RENAULT; Suite 1600; 1981 McGill College Ave. Montreal; QC; H3A 2Y3; CA Patent Application Number: 20030176406 Date filed: December 10, 2002 Abstract: The present invention relates to non-cross-linked micelles as delivery vehicles for steroid compounds and more particularly to a polycaprolactone-b-poly(ethylene oxide) copolymer micelle as a delivery vehicle for steroids. The delivery system comprises a population of diblock copolymer non-cross-linked micelles, each micelle defining a non-cross-linked core for containing the steroid compound. The delivery system of the present invention maintains the release of the steroid compound in a patient having a deficient steroid level. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/577,936 filed on May 25, 2000, which is still pending and which is hereby incorporated by reference. The present invention relates to non-cross-linked micelles as delivery vehicles and more particularly to polycaprolactone-b-poly(ethyle- ne oxide) copolymer noncross-linked micelles as delivery vehicles for steroids. In recent years, there has been much interest in the use of androgen replacement therapy for treating a variety of clinical indications. Currently, the most common use is for the treatment of men with hypogonadism, in which case testosterone production falls below a normal range of 3-10
Patents 429
mg/day. Hypogonadism is characterized by a loss of muscle and bone mass, an increase in visceral fat, impaired immune function and altered mood. Other accepted indications requiring androgen replacement therapy are microphallus in infants and delayed puberty in boys. Presently, androgen therapy is under investigation for the treatment of aging men with low to normal testosterone levels. Serum testosterone levels have been shown to decline with aging in men. This decline is gradual in comparison to the decline in production of oestrogen in postmenopausal women and there is much interindividual variation. The issue of androgen supplementation in aging men requires further investigation in order to ensure that the benefits do outweigh the risk posed to the cardiovascular system and the prostate. However, results from studies on aging men given androgen replacement therapy have been quite promising. Androgen replacement therapy is also being considered for the treatment of postmenopausal women and individuals in wasting states owing to their affliction with HIV, cancer or chronic infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for making estra-4,9(10)-diene steroids Inventor(s): Hessler, Edward J. (Kalamazoo, MI), Rheenen, Verlan H. Van; (Portage, MI) Correspondence: MACMILLAN SOBANSKI & TODD, LLC; ONE MARITIME PLAZA FOURTH FLOOR; 720 WATER STREET; TOLEDO; OH; 43604-1619; US Patent Application Number: 20030004333 Date filed: June 6, 2002 Abstract: A novel process for making estra-4,9(10)-diene-3,17-dione steroids from readily available 19-nor-androst-4-ene-3-one steroids by a straightforward three-step process. Products of this process are important intermediates in the preparation of biologically active substances. Excerpt(s): This application claims the benefit of U.S. provisional application Ser. No. 60/296,999, filed Jun. 8, 2001. Estra-3-keto-4,9(10)-diene steroids (all steroids herein have the natural stereochemistry unless otherwise defined), the products of this invention, are known valuable intermediates to biologically active substances (see G. Teutsch in Adrenal Steroid Antagonism, 5d. M. K. Agarwal, W. deGruyter and G. Berlin, 1984, pp. 43-75). U.S. Pat. No. 3,461,118 prepares this 3-keto-4,9(10)-diene structural feature from a 3-keto-.DELTA.5(10)-steroid by a process using bromine and pyridine. In the patent, the 3-keto-.DELTA.5(10)-steroid is produced by hydrolysis of the corresponding ketal, but it also can be made by many chemical routes (see CAN 69:77598; NL 6608779), most prominent among them by a Birch reduction of the 3-protected estrone followed by hydrolysis (see CAN 66:65723, NL 6607002). In French Patent 1,568,711, this same 3-keto starting material, estra-5(10)-ene-3-one steroid, is converted into the subject estra-3-keto4,9(10)-diene steroids, by a chlorination or iodination process as well as a process of epoxidation, epoxide opening under strongly basic conditions (i.e. potassium hydroxide in refluxing methanol), to produce the 10-hydroxy-estra-4-ene-3,17-dione which is an intermediate of the present invention. This intermediate is carried on by methane sulfonate ester formation followed by treatment with sodium acetate in acetic acid, a process very different from the present invention, and using a starting material different from the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for obtaining 17 beta-(N-tert-butylcarbamoyl)-3-one4-aza-steroids Inventor(s): Silva Guisasola, Luis Octavio; (Boecillo, ES), Blanco Fernandez, Cristina; (Boecillo, ES), Bonde-Larsen, Antonio Lorente; (Boecillo, ES), Martin Juarez, Jorge; (Boecillo, ES) Correspondence: AKIN, GUMP, STRAUSS, HAUER & FELD, L.L.P. ONE COMMERCE SQUARE; 2005 MARKET STREET, SUITE 2200; PHILADELPHIA; PA; 19103; US Patent Application Number: 20010008895 Date filed: March 5, 2001 Abstract: 17.beta.-(N-tert-butylcarbamoyl)-3-one-4-aza-steroids (I) can be obtained by a process which comprises the reaction of 17.beta.-(alkoxycarbonyl)-3-- one-4-aza-steroid with lithium tert-butylamide in an organic solvent. Some compounds of formula (I), for example, finasteride, are useful as inhibitors of 5.alpha.-reductase, and can be used in the treatment of benign prostatic hyperplasia and alopecia. 1 Excerpt(s): This invention relates to a process for obtaining 17.beta.-(N-tertbutylcarbamoyl) -3-one-4-aza-steroids, optionally unsaturated between carbons 1-2 or 56, useful as inhibitors of 5.alpha.-reductase or synthetic intermediates thereof. 4-azasteroids are known that are useful as inhibitors of the enzyme 5.alpha.-reductase, an enzyme that converts testosterone into the more potent androgen, 5.alpha.-dihydrotestosterone, which is the main mediator of the androgenic activity in some organs. The inhibitors of testosterone-5.alpha.-reductase may prevent or reduce the symptoms of hyperandrogenic stimulation. U.S. Pat. No. 4,760,071 describes some 17.beta.-(N-alkylcarbamoyl)- -4-aza-5.alpha.-androst-1-en-3-ones useful as inhibitors of 5.alpha.reductase. A representative example of said compounds is finasteride [17.beta.-(N-tertbutyl-carbamoyl)-4-aza-5.alpha.-androst-1-e- n-3-one], an active substance with multiple therapeutic applications, for example, in the treatment of benign prostatic hyperplasia and alopecia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process improvements in steroid chemistry Inventor(s): Ji, Gueijun; (Richmond, CA), Shen, Yaping; (Port Coquitlam, CA), Zhou, Yuanlin; (Richmond, CA), Kelleher, Eugene W. (Arlington, MA), Ramachandran, Kishore; (Burlington, MA), Paschalides, Nicholas D. (Roslindale, MA), Burgoyne, David L. (Delta, CA) Correspondence: SEED INTELLECTUAL PROPERTY LAW GROUP PLLC; 701 FIFTH AVE; SUITE 6300; SEATTLE; WA; 98104-7092; US Patent Application Number: 20030050286 Date filed: May 22, 2002 Abstract: Steroids containing a cyclohexene moiety are efficiently oxidized to the corresponding.alpha.,.beta.-unsaturated ketone using copper iodide and t-butyl hydroperoxide. A steroid compound containing the.alpha.,.beta.-unsaturated ketone structure is efficiently converted to the corresponding vicinal diol using a hydroborating reagent followed by oxidative workup, e.g., borane followed by sodium perborate. Benzoyl and substituted benzoyls are superior protecting groups for hydroxyl groups present in the compounds.
Patents 431
Excerpt(s): The present invention is directed to synthetic manipulations of organic chemicals, and particularly to the chemical reactions of steroids, and to steroids that may be used as starting materials in various chemical reactions, and to steroids that result from the chemical reactions. Steroid structures are commonly used as therapeutic agents. See, e.g., PCT International Publication No. WO 98/02450 and U.S. Pat. No. 6,046,185, among many other documents that discuss the therapeutic efficacy of steroids. Accordingly, there is a need in the art for efficient synthetic reactions that can prepare steroids of a desired structure. The present invention is directed to fulfilling this and related needs as described in detail herein. The present invention provides general synthetic methodology that may be employed to prepare steroid compounds having certain specified chemical functionality. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
SERUM-AND STEROID-FREE CULTURE MEDIA FOR CEREBELLAR GRANULE NEURONS Inventor(s): Belcher, Scott M. (Little Rock, AR) Correspondence: Christine J. Daugherty; WRIGHT, LINDSEY & JENNINGS LLP; 320 North Rollston, Suite 102; Fayetteville; AR; 72701; US Patent Application Number: 20020132345 Date filed: August 9, 2001 Abstract: The invention is a system for maintenance and high-throughput analysis of cerebellar granule neurons in tissue culture plates under chemically defined conditions. The invention includes serum-free granule culture medium, which is composed of high glucose Dulbecco's Modified Eagle Media (DMEM), NaHCO3, sodium pyruvate, and HEPES, which is subsequently adjusted to pH 7.2. The HEPES buffered DMEM is then supplemented with L-glutamine, KCl, bovine albumin, insulin, transferrin, selenium, penicillin, and streptomycin. Unlike proprietary neuronal culture media, this invention does not include any serum, steroid hormones, phenol red, or added anti-oxidants. The serum-free granule culture medium is then placed in conventional poly-lysine coated tissue culture plates in order to conduct subsequent assays. The invention also includes the ability to package the complete neuronal culture system into a "kit" for isolation, maintenance, treatment, and analysis of cerebellar neurons. A kit would include all the necessary culture medium preparations, tissue culture plates with an appropriate cellular attachment matrix, reagents, disposables and protocols. The kit could be used to evaluate neuronal viability, growth, the role of steroid hormones on neuronal function, drug or toxicant-induced changes in gene expression, or other bioassays. In addition, the invention will be useful in the field of pharmocogenomics because of the ability to analyze small sample sizes. Excerpt(s): The present application claims the benefit of U.S. provisional patent application No. 60/275,767, filed Mar. 14, 2001, which is incorporated herein by reference. The present invention relates to neuronal culture media that may be used for high-throughput analyses. The ability to maintain isolated neurons in primary culture has been critical in advancing our understanding of the functional basis of the nervous system. In primary neuronal culture studies, the use of defined culture conditions is essential for controlling the concentration of components, such as hormones and growth factors, which may affect the growth and development of cultured neurons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Steroid compounds, use of these compounds for the preparation of meiosisregulating medicaments and method for the preparation of these compounds Inventor(s): Esperling, Peter; (Berlin, DE), Blume, Thorsten; (Berlin, DE), HegeleHartung, Christa; (Mulheim/Ruhr, DE) Correspondence: MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BLVD. SUITE 1400; ARLINGTON; VA; 22201; US Patent Application Number: 20020188143 Date filed: March 26, 2002 Abstract: The present invention relates to steroid compounds of general formula X, which may advantageously be employed to stimulate meiosis in human oocytes, the steroid being specifically characterized by amino nitrogen bonded to C.sup.17 of the steroid skeleton via a spacer A. 1 Excerpt(s): The invention relates to pharmaceutically active steroid compounds, pharmaceutical compositions comprising these compounds, the use of these compounds for the preparation of a pharmaceutical composition being suitable to regulate reproduction, especially meiosis, of a contraceptive or as a profertility drug, a method for regulating reproduction, e.g. meiosis, a method for improving the possiblity of an oocyte's ability to develop into a mammal as well as methods for the preparation of the novel steroid compounds. Meiosis is the unique and ultimate event of germ cells, on which sexual reproduction is based. Meiosis comprises two meiotic divisions. During the first division, exchange between maternal and paternal genes take place before the pairs of chromosomes are separated into the daughter cells. These contain only half the number (1n) of chromosomes and 2c DNA. The second meiotic division proceeds without a DNA synthesis. This division therefore results in the formation of the haploid germ cells with only 1c DNA. The meiotic events are similar in the male and female germ cells, but the time schedule and the differentiation processes, which lead to ova and to spermatozoa differ profoundly. All female germ cells enter the prophase of the first meiotic division early in life, often before birth, but all are arrested as oocytes later in the prophase (dictyate state) until ovulation after puberty. Thus, from early life the female has a stock of oocytes, which is drawn upon until the stock is exhausted. Meiosis in females is not completed until after fertilization, and results in only one ovum and two abortive polar bodies per germ cell. In contrast, only some of the male germ cells enter meiosis from puberty and leave population of germ cells throughout life. Once initiated, meiosis in the male cell proceeds without significant delay and produces four spermatozoa. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Steroid derived antibiotics Inventor(s): Savage, Paul B. (Springville, UT), Li, Chunhong; (Provo, UT) Correspondence: JOHN W. FREEMAN, ESQ. Fish & Richardson P.C. 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020091278 Date filed: August 15, 2001
Patents 433
Abstract: A series of novel steroid derivatives are described. The steroid derivatives are antibacterial agents. The steroid derivatives also act to sensitize bacteria to other antibiotics including erythromycin and novobiocin. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/234,008, filed Jan. 19, 1999, which is a continuation-in-part of PCT/US 98/04489, filed Mar. 6, 1998, each of which is hereby incorporated by reference in its entirety. This application claims priority from provisional application U.S. No. 60/225,467, filed Aug. 15, 2000, which is hereby incorporated by reference in its entirety. The invention relates to novel steroid derivatives and processes and intermediates for the preparation of these compounds. Some compounds that associate strongly with the outer membrane of Gram-negative bacteria are known to disrupt the outer membrane and increase permeability. The increased permeability can increase the susceptibility of Gramnegative bacteria to other antibiotics. The best studied of this type of compound are the polymyxin antibiotics. For an example of a study involving the binding of polymyxin B to the primary constituent of the outer membrane of Gram-negative bacteria (lipid A) see: D. C. Morrison and D. M. Jacobs, Binding of Polymyxin B to The Lipid a Portion of Bacterial Lipopolysaccharides, Immunochemistry 1976, vol. 13, 813-819. For an example of a study involving the binding of a polymyxin derivative to Gram-negative bacteria see: M. Vaara and P. Viljanen, Binding of Polymyxin B Nonapeptide to Gram-negative Bacteria, Antimicrobial Agents and Chemotherapy, 1985, vol. 27, 548-554. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Steroid hormone binding protein Inventor(s): Hirata, Yuichi; (Niihari-gun, JP) Correspondence: JANIS K. FRASER, PH.D., J.D. Fish & Richardson P.C. 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020177194 Date filed: June 7, 2002 Abstract: Several ESTs deduced as a part of a cDNA encoding a protein that is homologous with a membrane-bound steroid binding protein PMBP were found. Based on the sequence data of these ESTs, a consensus sequence was extracted, and primers were designed based on this consensus sequence. Using the thus designed primers, a polymerase chain reaction of human genes was effected. As a result, a gene encoding a novel steroid hormone binding protein that is homologous with PMBP was successfully isolated from a human for the first time. Excerpt(s): This is a continuation-in-part of PCT/JP98/05010, filed Nov. 6, 1998, and claims priority from Japanese Patent Application No. 9/322376, filed Nov. 7, 1997. The present invention relates to steroid hormone binding proteins, genes thereof, and production and use of the proteins and the genes. It is generally thought that steroid hormones exert their physiological influence by regulating transcriptional activities. Very recently, however, steroids that exhibit their activities rapidly without acting on genes have become widely known, but this cannot be explained by the above theory. Evidence of this rapid action of steroids has been shown for every steroid in many species and tissues. Examples include the rapid action of aldosterone on lymphocytes and vascular smooth muscle (Wehling, M. (1995) Cardiovasc. Res. 29(2), 167-171), vitamin D3 on epithelial cells, progesterone on sperm (Revelli, A. Modotti, M. PiffarettiYanez, A. Massobrio, M. and Balerna, M. (1994) Hum Reprod 9 (5), 760-766),
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neurosteroids on neurons, and estrogen on blood vessels. The signal recognition and transduction mechanisms of these activities are currently being studied. As a result, it is now becoming clear that the signal recognition and transduction system resembles cascade systems of membrane receptors and the second messengers, such as those of catecholamines and peptide hormones, since many of the activities depend on phospholipase C, phosphoinositide turnover, intracellular pH, intracellular calcium, protein kinase C, tyrosine kinases, etc., (Baran, D. T. (1994) J Cell Biochem 56 (3), 303306; de Boland, A. R. and Nemere, I. (1992) J Cell Biochem 49 (1), 32-36). Although the physiological or pathological relevance is not clear, it has been presumed that the rapid action of steroids can also be observed in vivo in the cardiovascular system, the central nervous system, and the reproductive system. It was expected that these receptors would be cloned soon and that the relationship between the rapid action of steroids and their clinical effects would be clarified (Wehling, M. (1997) Annu Rev Physiol 59, 365393; and Wehling, M. (1995) J Mol Med 73 (9), 439-447). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Steroid hormone products and methods for preparing them Inventor(s): Clark, Bradley A. (Gurnee, IL), Falzone, Angela; (Raritan, NJ), Schultz, Thomas; (Richboro, PA) Correspondence: AUDLEY A. CIAMPORCERO JR. JOHNSON & JOHNSON; ONE JOHNSON & JOHNSON PLAZA; NEW BRUNSWICK; NJ; 08933-7003; US Patent Application Number: 20020173669 Date filed: December 13, 2001 Abstract: The present invention relates to steroid hormone products, such as oral contraceptive products, including at least one steroid active ingredient mixed with an excipient and having improved dissolution and release rate properties. The invention further relates to methods for making such steroid hormone products, wherein a mixture of the hormone and the excipient is subjected to sufficient mechanical energy to form a powder blend wherein the hormone is stabilized by the excipient in substantially non-crystalline form. Excerpt(s): The present invention relates to steroid hormone products comprising at least one steroid active ingredient mixed with an excipient and having improved dissolution and release rate properties. More particularly, the invention provides an oral contraception product having an improved dissolution profile. The invention further relates to methods for making such steroid hormone products, either with or without the use of solvents. As used herein, the term "steroid hormone product" is a physically discrete unit suitable as a unitary dosage for a human host. The product contains a predetermined quantity of at least one steroid active ingredient effective to produce a desired effect. Examples, of such products are tablets, capsules, caplets, pills or discrete quantities of powder. Oral contraceptives first became available in the early 1960's. Since then, a number of regimens for controlling ovulation and contraception by the administration of hormones have become known and are readily available. Oral contraceptive formulations typically contain an estrogen and a progestin. In addition to these steroid active ingredients, the formulation may contain an excipient including various grades of lactose, additives and fillers such as pregelatinized starch and magnesium stearate, and a colorant such as an aluminum oxide lake. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 435
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Steroid hormone receptor polynucleotides, polypeptides, and antibodies Inventor(s): Ni, Jian; (Germantown, MD), Shi, Yanggu; (Gaithersburg, MD), Ruben, Steven M. (Olney, MD) Correspondence: HUMAN GENOME SCIENCES INC; 9410 KEY WEST AVENUE; ROCKVILLE; MD; 20850 Patent Application Number: 20020165384 Date filed: March 22, 2002 Abstract: The present invention relates to novel human steroid hormone receptor polypeptides and isolated nucleic acids containing the coding regions of the genes encoding such polypeptides. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human steroid hormone receptor polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human steroid hormone receptor polypeptides. Excerpt(s): This application is a continuation of and claims priority under 35 U.S.C.sctn.120 to U.S. application Ser. No. 09/805,204, filed Mar. 14, 2001, which is a continuation-in-part of and claims priority under 35 U.S.C.sctn.120 to International Application No. PCT/US00/24517, filed Sep. 7, 2000, which claims benefit under 35 U.S.C.sctn.119(e) of U.S. Provisional Application Nos. 60/152,932, filed Sep. 9, 1999, and 60/189,032, filed Mar. 14, 2000, all of which are hereby incorporated by reference in their entireties. The present invention relates to novel steroid hormone receptor proteins. More specifically, isolated nucleic acid molecules are provided encoding novel steroid hormone receptor polypeptides. Novel steroid hormone receptor polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human steroid hormone receptor polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to these novel steroid hormone receptor polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention. Physiological and therapeutic activities of steroid hormones are mediated by the family of steroid hormone receptor proteins, which are members of the nuclear receptor family of proteins. These nuclear receptors include the receptors for steroids, thyroid hormone, vitamins A and D-derived hormones, and certain fatty acids (Kumar, R., and E. B. Thompson, Steroids, 64:310-19 (1999)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Steroid sulfatase inhibitors and methods for making and using the same Inventor(s): Murakata, Chikara; (Shizuoka-Ken, JP), Akinaga, Shiro; (Shizuoka-Ken, JP), Li, Pui-Kai; (Galloway, OH) Correspondence: ECKERT SEAMANS CHERIN & MELLOTT; 600 GRANT STREET; 44TH FLOOR; PITTSBURGH; PA; 15219 Patent Application Number: 20020068726 Date filed: November 8, 2001 Abstract: Novel sulfatase inhibitor compounds useful in the treatment of estrogen dependent illnesses are disclosed. These compounds generally comprise a steroid nucleus substituted at the C17 position. Methods for synthesizing these compounds and using them in the therapeutic and/or prophylactic treatment of a patient are also disclosed. Excerpt(s): This is a continuation-in-part of U.S. Ser. No. 09/236,842, filed on Jan. 25, 1999. The present invention relates to sulfatase inhibitors and methods for making and using the same. These methods include use of these compounds in therapeutic and prophylactic treatments for estrogen dependent illnesses. Estrogen levels in breast tumors of post-menopausal women are at least ten times higher than estrogen levels in plasma. The high levels of estrogen in these tumors are due to in situ formation of estrogen, possibly through conversion of estrone sulfate to estrone by the enzyme estrone sulfatase. Inhibitors of estrone sulfatase are therefore potential agents for the treatment of estrogen-dependent breast cancers. Most estrone sulfatase inhibitors are steroidal in nature. Although estrone-3-O-sulfamate (EMATE) is believed to be the most potent inhibitor of estrone sulfatase, recent evidence indicates that this compound is a potent estrogen. This compound is therefore not useful in the treatment of estrogen dependent illnesses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Steroid sulphatase inhibitors Inventor(s): Potter, Barry Victor Lloyd; (Avon, GB), Reed, Michael John; (London, GB) Correspondence: FROMMER LAWRENCE & HAUG; 745 FIFTH AVENUE- 10TH FL. NEW YORK; NY; 10151; US Patent Application Number: 20020177619 Date filed: February 21, 2002 Abstract: A method for controlling estrogen production comprising administering a ring system compound comprising a sulphamic acid ester group; wherein said compound is an inhibitor of an enzyme having steroid sulphatase activity (EC 3.1.6.2); and wherein if the sulphamic acid ester group of said compound is replaced with a sulphate group to form a sulphate compound and incubated with a steroid sulphatase enzyme (EC 3.1.6.2) at a pH 7.4 and 37.degree. C. it provides a K.sub.m value of less than 50.mu.M. A method to target the estrogen metabolic pathway comprising administering a ring system compound comprising a sulphamic acid ester group; wherein said compound is an inhibitor of an enzyme having steroid sulphatase activity (EC 3.1.6.2); and wherein if the sulphamic acid ester group of said compound is replaced with a sulphate group to form a sulphate compound and incubated with a steroid sulphatase enzyme (EC 3.1.6.2) at a pH 7.4 and 37.degree. C. it provides a K.sub.m value of less than 50.mu.M.
Patents 437
Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/111,927, which is a continuation-in-part of U.S. application Ser. No. 08/458,352 which was a continuation of U.S. application Ser. No. 08/196,192 which was derived from PCT/GB92/01587 which was originally published as WO 93/05064; all of which are incorporated herein by reference. This application is also a continuation-in-part of U.S. application Ser. No. 09/142,194 and PCT patent application number PCT/GB97/00600 filed on Mar. 4, 1997 and published as WO 97/32872 and which designates the USA, the contents of which are incorporated herein by reference. This application is also a continuation-in-part of U.S. application Ser. No. 09/125,255 and PCT patent application number PCT/GB97/00444 filed on Feb. 17, 1997 and published as WO 97/30041 and which designates the USA, the contents of which are incorporated herein by reference. This application is also a continuation-in-part of PCT patent application number PCT/GB97/03352 filed on Dec. 4, 1997 and published as WO 98/24802 and which designates the USA, the contents of which are incorporated herein by reference. This invention relates to novel compounds for use as steroid sulphatase inhibitors, and pharmaceutical compositions containing them. Steroid precursors, or pro-hormones, having a sulphate group in the 3-position of the steroid nucleus, referred to hereinafter simply as steroid sulphates, are known to play an important part as intermediates in steroid metabolism in the human body. Oestrone sulphate and dehydroepiandrosterone (DHA) sulphate, for example, are known to play an important role as intermediates in the production, in the body, of oestrogens such as oestrone and oestradiol. Oestrone sulphate, in particular, is known, for example, to represent one of the major circulating oestrogen precursors particularly in post-menopausal women and oestrone sulphatase activity in breast tumours is 100-1000 fold greater than that of other enzymes involved in oestrogen formation (James et al., Steroids, 50, 269-279 (1987)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Steroid sulphatase inhibitors Inventor(s): Reed, Michael John; (London, GB), Potter, Barry Victor; (Avon, GB) Correspondence: FROMMER LAWRENCE & HAUG; 745 FIFTH AVENUE- 10TH FL. NEW YORK; NY; 10151; US Patent Application Number: 20020128243 Date filed: February 25, 2002 Abstract: A method of inhibiting steroid sulphatase activity in a subject in need of same is described.The method comprises administering to said subject a steroid sulphatase inhibiting amount of a ring system compound; which ring system compound comprises a ring to which is attached a sulphamate group of the formula 1wherein each of R.sub.1 and R.sub.2 is independently selected from H, alkyl, alkenyl, cycloalkyl and aryl, or together represent alkylene optionally containing one or more hetero atoms or is groups in the alkylene chain; and wherein said compound is an inhibitor of an enzyme having steroid sulphatase activity (E.C.3.1.6.2); and if the sulphamate group of said compound is replaced with a sulphate group to form a sulphate compound and incubated with a steroid sulphatase enzyme (E.C.3.1.6.2) at a pH 7.4 and 37.degree. C. it would provide a K.sub.m value of less than 50.mu.M. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 08/458,352 which was a continuation of U.S. application Ser. No. 08/196,192 which was derived from PCT/GB92/01587 which was originally published as WO 93/05064. This application is also a continuation-in-part of PCT patent application No.
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PCT/GB97/00600 filed on Mar. 4, 1997 and published as WO 97/32872 and which designates the USA--the contents of which are incorporated herein by reference. This application is also a continuation-in-part of PCT patent application No. PCT/GB97/00444 filed on Feb. 17, 1997 and published as WO 97/30041 and which designates the USA--the contents of which are incorporated herein by reference. This application is also a continuation-in-part of PCT patent application No. PCT/GB97/03352 filed on Dec. 4, 1997 and published as WO 98/24802 and which designates the USA--the contents of which are incorporated herein by reference. This invention relates to novel compounds for use as steroid sulphatase inhibitors, and pharmaceutical compositions containing them. Steroid precursors, or pro-hormones, having a sulplhate group in the 3-position of the steroid nucleus, referred to hereinafter simply as steroid sulphates, are known to play an important part as intermediates in steroid metabolism in the human body. Oestrone sulphate and dehydroepiandrosterone (DHA) sulphate, for example, are known to play an important role as intermediates in the production, in the body, of oestrogens such as oestrone and oestradiol. Oestrone sulphate, in particular, is known, for example, to represent one of the major circulating oestrogen precursors particularly in post-menopausal women and oestrone sulphatase activity in breast tumorous is 100-1000 fold greater than that of other enzymes involved, in oestrogen formation (James et al., Steroids, 50, 269-279 (1987)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Synergistic activation of regulatory elements by rel proteins and a steroid receptor Inventor(s): Boersma, Christine J.C. (Oosterbeek, NL), Wissink, Sacha; (Hertogenbosch, NL), Van Der Burg, Bart; (Houten, NL), Van Der Saag, Paulus Theodorus Maria; (EA Maarn, NL) Correspondence: William M Blackstone; Akzo Nobel; Patent Department Intervet Inc; 405 State Street; Millsboro; DE; 19966; US Patent Application Number: 20030119717 Date filed: November 18, 2002 Abstract: Interaction of Rel proteins and steroid receptors is known to result in repression of target genes. Here we describe the discovery of a new mechanism in which Rel proteins and steroid receptors act synergistically to activate a regulatory element. This mechanism is shown to influence the expression of the brain-specific 5HT1A receptor wherein the estrogen receptor acts synergistically with the Nuclear Factor kappa B to enhance the activity of the promoter for the 5HT1A receptor gene. In addition, synergistic effects of Rel proteins with the mineralocorticoid receptor were observed, showing that synergism with Rel proteins may be expected for other steroid receptors as well. The synergism between Rel proteins and estrogen receptor or mineralocorticoid receptor provides a tool for the development of compounds that interact with the estrogen or mineralocorticoid receptor in such a way that only the synergistic effect is modulated whereas other effects are left intact. Such compounds would be invaluable for the development of medicaments for the treatment of diseases of the central nervous or cardiovascular system and other disorders in which Rel proteins play a role. Excerpt(s): The invention relates to a method for the identification of compounds capable of modulating a newly discovered-mechanism whereby a steroid receptor and a Rel protein act synergistically to activate a regulatory element. The invention also relates to a cell transfected with nucleic acid and the use of that cell in an assay for the
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identification of compounds that modulate the level of gene expression under the control of the regulatory element as well as the medical use of compounds identified in such an assay. Members of the Nuclear Factor-.kappa.B (NF-.kappa.B)/Rel family of transcription activator proteins are tightly associated with their inhibitory proteins (I.kappa.B) and reside in the cytoplasm. They can be induced by pro-inflammatory cytokines and are important in immunological and inflammatory processes because they direct transcription of chemoattracants, cytokines (including the NF-.kappa.B induced cytokines themselves), cytokine receptors and cell adhesion molecules. Upon induction, rel proteins dimerize and migrate to the nucleus where they activate their target genes through an NF-.kappa.B binding motif in the promoter of these genes. Examination of DNA sequences recognized by different NF-.kappa.B dimers reveals that the prefered target sites are slightly different for the existing dimer combinations of rel proteins (Chen et al., Nature Struct. Biol. 5: 67-73, 1998; Kunsch et al., Mol. Cell Biol. 12: 4412-4421, 1992; Parry and Mackman, J. Biol. Chem. 269: 20823-20825, '94), explaining the broad variation in NF.kappa.B responsive elements that have been identified in various promoters. Dimerization and nuclear translocation of Rel proteins is induced by a large number of agents including bacterial and viral pathogens, immune and inflammatory cytokines and a variety of agents that damage cells. An even larger number of genes appear to be targets for the activation by Rel proteins, as this family of transcription factors has been found to interact with steroid receptors such as estrogen receptors and glucocorticoid receptors, resulting in repression of target genes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Synthesis of anti-estrogenic and other therapeutic steroids from 21-hydroxy-19norpregna-4-en-3-one Inventor(s): Tanabe, Masato; (Palo Alto, CA), Ryan, Kenneth J. (Sunnyvale, CA), Peters, Richard H. (San Jose, CA), Chao, Wan-Ru; (Sunnyvale, CA), Liu, Jyanwei; (Sunnyvale, CA), Johansson, John G. (Menlo Park, CA) Correspondence: REED & ASSOCIATES; 800 MENLO AVENUE; SUITE 210; MENLO PARK; CA; 94025; US Patent Application Number: 20010039269 Date filed: February 9, 2001 Abstract: Syntheses of steroids such as 3-hydroxy-7.alpha.-methyl-21-[2'-methoxy-4'-(diethylaminomethyl)-phenoxy]-19-norpregna-1,3,5(10)triene citrate ("SR 16234") and analogs thereof are provided, wherein 21-hydroxy-19-norpregna- -4-en-3-one serves as a starting material or intermediate. The latter compound may be readily prepared from estrone-3-methyl ether. Certain intermediates in these syntheses also have value as therapeutic agents, for example in the treatment of prostate disorders such as prostatic cancer. Excerpt(s): This application claims priority to provisional U.S. patent application Ser. No. 60/181,738, filed Feb. 11, 2000. This invention relates generally to the chemical synthesis of steroids, and more particularly relates to the synthesis of anti-estrogenic and other therapeutic steroids such as 3-hydroxy-7.alpha.-methyl-21-[2'-methoxy-4'(diethylaminomethyl)-phenoxy]- -19-norpregna-1,3,5(10)triene citrate ("SR 16234") and analogs thereof. The invention additionally relates to starting materials and intermediates useful in conjunction with the novel synthesis. Breast cancer is one of the most prevalent types of cancer, and epidemiological and clinical studies have shown that approximately two-thirds of breast tumors are estrogen-dependent. This means that
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estrogens are required for the growth of such breast tumors in both premenopausal and postmenopausal patients. In postmenopausal women, in whom breast cancer most commonly occurs, breast tumor concentrations of estrone and estradiol are considerably higher than blood estrogen levels. Although retention of estrogens in breast tumors by high-affinity binding proteins contributes to the level of estrogens in tumors, estrogen concentrations in the breast are higher than plasma levels in breast cancer patients regardless of whether their tumors are estrogen receptor-positive (ER+) or estrogen receptor-negative (ER-). In situ formation of estrogen from estrogen biosynthetic precursors within tumors is now known to make a major contribution to the estrogen content of breast tumors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Transdermal administration of steroid drugs using hydroxide-releasing agents as permeation enhancers Inventor(s): Luo, Eric C. (Plano, TX), Hsu, Tsung-Min; (San Diego, CA) Correspondence: REED & EBERLE LLP; 800 MENLO AVENUE, SUITE 210; MENLO PARK; CA; 94025; US Patent Application Number: 20030157157 Date filed: February 20, 2003 Abstract: A method is provided for increasing the permeability of skin or mucosal tissue to transdermally administered steroid drugs. The method involves use of a specified amount of a hydroxide-releasing agent, the amount optimized to increase the flux of the drug through a body surface while minimizing the likelihood of skin damage, irritation or sensitization. Formulations and drug delivery systems for co-administering a hydroxide-releasing agent with a steroid drug are provided as well. Optimally, the steroid drugs are a combination of an estrogen and progestin that may be administered in female hormone replacement therapy, to provide female contraception, and the like Excerpt(s): This is a divisional application of U.S. Ser. No. 09/737,833, filed Dec. 14, 2000; which is a continuation-in-part of U.S. Ser. No. 09/569,889, filed May 11, 2000, now abandoned; which is a continuation-in part of U.S. Ser. No. 09/465,098, filed Dec. 16, 1999, now abandoned; the disclosures of which are incorporated by reference. This invention relates generally to transdermal administration of pharmacologically active agents, and more particularly relates to methods and compositions for transdermally administering steroid drugs, particularly progestins and estrogens. The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences , e.g., gastrointestinal irritation and the like, are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of 1,4-androstadienedione as a method anabolic/androgenic steroid boldenone in humans
of
increasing
levels
of
the
Inventor(s): Llewellyn, William Charles; (Sound Beach, NY) Correspondence: William Llewellyn; PO Box 1162; Sound Beach; NY; 11789; US Patent Application Number: 20030027805 Date filed: July 25, 2002 Abstract: This invention discloses a method of administering 1,4-androstadienedione as a means of increasing boldenone levels in humans. As men age, a decline in androgenic hormone levels is typically noted, possibly resulting in muscle mass, bone density and energy loss. Various methods have therefore been developed to supplement androgens for men with declining levels. This invention is an improvement over the previously suggested steroid precursors, in that androstadienedione displays superior oral activity. This may be a very advantageous trait for men seeking the an orally active form of androgen replacement. Excerpt(s): Continuation in-part of application Ser. No. 09/641,526, now abandoned. Androgens are responsible for the development and maintenance of male sexual characteristics, including external virilization, sexual maturity at puberty, spermatogenesis, sexual behavior/libido and erectile functioning. They also supports bone and muscle tissue growth, and remains vital to ones health and well being throughout life. After physical maturity, men often notice a slow decline in the level of androgens produced by the body. Dubbed andropause, subnormal androgen levels can lead to a decline in muscle mass, libido, sexual functioning and overall sense of well being later in life. In many instances this indicates a need for some form of androgen replacement. This invention relates a method of administering 1,4-androstadiene-3,17dione, as a means of obtaining an anabolically or androgenically active serum level of boldenone in humans. Boldenone is an anabolic/androgenic steroid structurally similar to the primary male androgen testosterone. Although similar in structure however, its action in the human body is measurably different from that of testosterone. The primary difference stems from the fact that boldenone is much more slowly aromatized to estradiol, and as a result this hormone displays less estrogenic activity than testosterone. Boldenone is also less active at promoting androgenic activity in target tissues where the 5-alpha reductase enzyme normally converts testosterone to its more potent form of dihydrotestosterone, as it is highly resistant to interaction with this enzyme. Being an active anabolic/androgenic steroid however, the activity of boldenone is still capable of inducing the expected benefits of androgen replacement on mood, sexual function, bone and muscle, as all such effects are mediated by the cellular androgen receptor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with steroids, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “steroids” (or synonyms) into the
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“Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on steroids. You can also use this procedure to view pending patent applications concerning steroids. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON STEROIDS Overview This chapter provides bibliographic book references relating to steroids. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on steroids include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “steroids” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on steroids: •
Conquering Rheumatoid Arthritis: The Latest Breakthroughs and Treatments Source: Amherst, NY: Prometheus Books. 2001. 255 p. Contact: Available from Prometheus Books. 59 John Glenn Drive, NY 14228-2197. (716) 691-0133 or (800) 421-0351. Website: www.prometheusbooks.com. PRICE: $20.00. ISBN: 1573928860. Summary: This book for patients describes the origins, disease course, and treatment of rheumatoid arthritis (RA). Rheumatoid arthritis affects over two million Americans. It is three times more common in women than men and becomes increasingly common in people as they age. RA is an inflammatory disease of the synovium, or lining of a joint, that results in pain, stiffness, swelling, joint damage, and loss of function in the joints. Chapters discuss the body's immune system; the anatomy of the synovial joints; the system by which the body's immune system attacks these joints; the genetic origins of RA and gene therapy; stem cell research and therapy; traditional treatments for RA
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including NSAIDS, DMARDS, and steroids; new medications including etanercept, COX-1 and COX-2 enzymes, leflunomide, and infliximab; clinical trials; and potential therapies. Appendices include related websites and a glossary. 14 figures. •
Exercise for Osteoporosis Source: Long Island City, NY: Hatherleigh Press. 2000. 144 p. Contact: Available from Hatherleigh Press. 5-22 46th Avenue, Long Island City, NY 11101. (800) 528-2550. Fax: (800) 621-8892. Website: www.hatherleighpress.com. Email:
[email protected]. Price: $14.95 plus shipping. ISBN: 1578260760. Summary: This book presents exercises that will help the osteoporosis patient strengthen their bones and improve their balance and flexibility. Osteoporosis is a disease that is characterized by abnormal loss of bone density. Although it is perceived that osteoporosis is a disease of older women, osteoporosis can affect men and women who are young or middle-aged. It is estimated that 25 million Americans suffer from osteoporosis and if preventive measures are not taken now, the incidence of this disease may double within 25 years. To prevent osteoporosis, the patient should stop smoking cigarettes, taking steroids, consuming large amounts of alcohol, and choose to eat a balanced diet and live an active lifestyle. Questions to determine osteoporosis risk are listed. Fractures most commonly occur at the wrist, spine, and hip. Exercise precautions are listed. The exercises in the book are divided into sections by body part: spine, hip, wrist, chest and arms, and abdominals. Each exercise is illustrated. In addition, exercises for balance and breathing are included. Suggested exercise routines are included as well as an equipment and resource list. 4 references and numerous pictures.
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Practical Psoriasis Therapy. Second Edition Source: St. Louis, MO: Mosby-Year Book, Inc. 1993. 322 p. Contact: Available from Mosby-Year Book, Inc., 11830 Westline Industrial Drive, St. Louis, MO 63416. Summary: This book for health professionals serves as a guide for physicians who manage patients with psoriasis. Chapters explain the differential diagnosis of psoriasis; describe the histopathology of psoriasis; discuss the selection of therapy for psoriasis patients; and examine the use of topical steroids and other topical agents, Coal tars, keratolytics, emollients, anthralin, phototherapy, psoralen ultraviolet A (PUVA) therapy, synthetic retinoids, systemic chemotherapy, and cyclosporine in the treatment of psoriasis. Chapters also discuss psoriasis day care centers and therapies for childhood psoriasis, scalp psoriasis, pustular psoriasis, exfoliative and erythrodermic psoriasis, nail psoriasis, and psoriatic arthritis. Appendices provide patients with information and instructions concerning topical therapies, topical corticosteroids, anthralin, ultraviolet phototherapy, home ultraviolet therapy, psoralen phototherapy, etretinate, methotrexate, cyclosporine, childhood psoriasis, and arthritic psoriasis. Numerous references, 22 figures, and 58 tables.
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Meniere's Disease: What You Need to Know Source: Portland, OR: Vestibular Disorders Association. 1998. 336 p. Contact: Available from Vestibular Disorders Association. P.O. Box 4467, Portland, OR 97208-4467. (800) 837-8428. E-mail:
[email protected]. Website: www.vestibular.org. PRICE: $24.95 plus shipping and handling. ISBN: 0963261118.
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Summary: This book provides information for people who have or suspect they have Meniere's disease and want to know more about its diagnosis and treatment, as well as strategies for coping with its effects. Written in nontechnical language, the book offers 40 chapters covering the anatomy of the normal ear, the physiology of hearing, balance and other vestibular functions, vision involvement, the symptoms of Meniere's disease, remission, late-stage Meniere's disease, diagnostic tests, hearing tests, indirect vestibular function tests, general treatment considerations, diet therapy, drug therapy, diuretics, drugs meant to block symptoms temporarily, steroids, drugs meant to block symptoms permanently, treatment for cochlear problems, alternative treatments, surgery, prognosis, compensation, coping, safety, preservation of hearing and balance function, research, the temporal bone bank, the members of the otologic health care team, insurance, where to get more information, and patient success stories. Each chapter concludes with references and the book concludes with a glossary of terms and a subject index. •
Angry Gut: Coping with Colitis and Crohn's Disease Source: New York, NY: Plenum Press. 1993. 350 p. Contact: Available from Plenum Publishing. 233 Spring Street, New York, NY 100131578. (800) 221-9369 or (212) 620-8000. Fax (212) 647-1898. E-mail:
[email protected]. PRICE: $26.95. ISBN: 0306444704. Summary: This book is intended for patients with inflammatory bowel disease (IBD), their families, and the nurses, primary care physicians, and other health professionals who work with these patients. Twenty-seven chapters are presented in five parts: understanding the anatomy and physiology of IBD; ulcerative colitis; Crohn's disease; special topics related to IBD; and treatments and investigations. Specific topics related to IBD include history; epidemiology; symptoms; diagnosis; treatment;and complications; variant colitis; extraintestinal manifestations; colon cancer; psychological factors and quality of life issues; sex and reproduction; nutrition; drug therapy, including 5-ASA, steroids, immunosuppressives, and antibiotics; surgery; and research. The volume includes some technical language and emphasizes a cooperative, team approach between patient and physician. A subject index is included.
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Evaluating and Managing Interstitial Cystitis Source: Englewood Cliffs, NJ: University Research Associates Rx, Inc. 1997. 47 p. Contact: Available from University Research Associates Rx, Inc. 560 Sylvan Avenue, Englewood Cliffs, NJ 07632. (201) 816-0110. PRICE: Contact distributor directly for current prices for professionals. Summary: This monograph reviews current concepts of the pathogenesis of interstitial cystitis (IC) as well as new methods to successfully diagnose and manage this disease. IC is characterized by severe urinary frequency, urgency, and lower abdominal or perineal pain in the absence of any bacterial infection or other definable pathology. IC also has mild and moderate states. IC typically has a gradual onset with an insidious progression. The author notes that it may be that IC encompasses a number of different etiologies, all involving a bladder insult that ultimately results in urinary frequency and urgency. An important purpose for using this broader definition of IC is that many patients with milder forms could readily benefit from therapy if the diagnosis is considered. One of the main diagnostic problems with IC is a lack of pathologic findings that are readily identified and quantified. Diagnostic procedures discussed include the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC, the use
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of a voiding log, the physical examination, urodynamics, the potassium test, cystoscopic inspection and hydrodistension, and biopsy. Treatment options covered include antidepressant therapy, hydrodistension of the bladder under anesthesia, dimethyl sulfoxide (DMSO) instillation, antihistamines, steroids, intravesical silver nitrate, sodium oxychlorosene, heparinoid therapy, pentosan polysulfate (Elmiron), and surgery. The author stresses that, when discussing therapy with the patient, it is important to emphasize that if symptoms have been present for more than a year, no particular therapy is likely to be curative. While the patient may have a significant remission of symptoms, in all probability relapse will occur. The author concludes that perhaps 75 to 85 percent of patients with moderate to severe IC can experience significant, indefinite remissions with conservative therapy and avoid the need for extirpative surgery. The monograph concludes with the package insert information for Elmiron. 3 figures. 6 tables. 105 references. (AA-M). •
Adolescent substance abuse and addictions Source: Philadelphia, PA: Hanley and Belfus. 1993. 477 pp. Contact: Available from Hanley and Belfus, 210 South 13th Street, Philadelphia, PA 19107. Telephone: (215) 546-4995. $63.00 for yearly subscription to three issues in the series. Summary: This book presents current review articles on the medical aspects of adolescent substance abuse and addiction. The topics include risk factors and behaviors; ethnic and cultural factors; office assessment by primary care physician; alcohol, nicotine, illicit drugs, anabolic steroids; drug testing; treatment issues; the influence of the media; influence of drug use on sexual activity; trauma and clinical issues; and psychiatric and developmental issues.
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Sports and the adolescent Source: Philadelphia, PA: Hanley and Belfus. 1991. 250 pp. Contact: Available from Hanley and Belfus, 210 South 13th Street, Philadelphia, PA 19107. Telephone: (215) 546-4995. Summary: This volume was written for primary care physicians who have a particular interest in adolescents and who are looking for information that will help them care for the young athletes in their practice. Topics discussed include the sport physical; medical exclusion from sport; menstruation; stress; status of adolescent fitness; steroids; death on the playing field; epidemiology of sport injuries; management of soft tissue injuries; head injuries; catastrophic head and neck injuries; overuse syndromes of the shoulder and arm, and overuse syndromes of the back and legs in adolescents.
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Oral Mucosal Disorders Source: Torrance, CA: Homestead Schools, Inc. 2000. 76 p. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail:
[email protected]. Website: www.homesteadschools.com. PRICE: $48.00 plus shipping and handling. Course No. 6480. Summary: Oral mucosal disorders are frequently encountered by the practicing dentist. This continuing education program for dentists focuses on oral mucosal disorders. Topics include the causes of chronic nonspecific mucosal lesions; recognized etiologic
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(causative) agents and their correlation with subtle lesional patterns; drugs commonly associated with lichenoid reactions; various dental materials known to cause oral allergic lesions; differential diagnosis, including medications associated with lichenoid reactions, dental materials, common sensitizers in dental materials, foods and oral health care products, atypical lichen planus, and candidiasis; approaches to the classification of oral mucosal lesions; the etiology, appearance, diagnosis, and treatment of the four most common forms of candidosis, i.e., pseudomembranous, erythematosus, hyperplastic, and angular cheilosis; systemic and local factors that predispose a patient to develop candidosis; herpes simplex virus infection and its clinical manifestations; instructions on the proper use of topical steroids for the treatment of minor recurrent aphthous ulcers; the symptoms and diagnosis of recurrent herpetic infection; and over the counter products that can be used for oral ulcerations, including covering agents, local anesthetics, oxygenating agents, and cauteries and antiseptics. The document concludes with a posttest with which readers can qualify for continuing education credit. The document is illustrated with numerous black and white photographs. 15 figures. 13 tables 77 references.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “steroids” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “steroids” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “steroids” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Adrenal Steroid Antagonism: Proceedings by M. K. Agarwal (Editor), Quebec) International Congress of Endocrinology 1984 Quebec (1985); ISBN: 3110100908; http://www.amazon.com/exec/obidos/ASIN/3110100908/icongroupinterna
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Adrenal steroids and disease by Cuthbert L. Cope; ISBN: 039758086X; http://www.amazon.com/exec/obidos/ASIN/039758086X/icongroupinterna
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ADV IN STEROID BIOCHEMISTRY V5; ISBN: 0120375052; http://www.amazon.com/exec/obidos/ASIN/0120375052/icongroupinterna
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Advances in Steroid Analysis (Proceedings of the Symposium, Eger, Hungary, 20-22, May, 1981) by S. Gorog (Editor) (1982); ISBN: 0444997113; http://www.amazon.com/exec/obidos/ASIN/0444997113/icongroupinterna
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Advances in steroid analysis '84 : proceedings of the 2nd Symposium on the Analysis of Steroids, Szeged, Hungary, June 12-14, 1984; ISBN: 9630541718; http://www.amazon.com/exec/obidos/ASIN/9630541718/icongroupinterna
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Advances in Steroid Analysis '84: Proceedings of the Symposium on the Analysis of Steroids, Szeged, Hungary, June 12-14, 1984 (Analytical Chemistry Symposia Series, V. 23) by Hungary)/ Gorog, S. Symposium on the Analysis of Steroids 1984 Szeged (Editor), S. Gorog (1986); ISBN: 0444995331; http://www.amazon.com/exec/obidos/ASIN/0444995331/icongroupinterna
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Advances in steroid analysis '87 : proceedings of the Symposium on the Analysis of Steroids, Sopron, Hungary, October 20-22, 1987; ISBN: 9630552299; http://www.amazon.com/exec/obidos/ASIN/9630552299/icongroupinterna
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Advances in Steroid Analysis '93: Proceedings from the 5th Symposium on the Analysis of Steroids Szombathely, Hungary, May 3-5, 1993 by S. Gorog (Editor) (1994); ISBN: 9630567210; http://www.amazon.com/exec/obidos/ASIN/9630567210/icongroupinterna
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Advances in Steroid Biochemistry & Pharmacology by M. H. Briggs (Editor), G. A. Christie (Editor); ISBN: 0120375060; http://www.amazon.com/exec/obidos/ASIN/0120375060/icongroupinterna
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Advances in Steroid Biochemistry and Pharmacology by M. H. and Christie, G. A. Briggs (Editor); ISBN: 012037501X; http://www.amazon.com/exec/obidos/ASIN/012037501X/icongroupinterna
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Advances Steroid Anal 89 (2002); ISBN: 9630560348; http://www.amazon.com/exec/obidos/ASIN/9630560348/icongroupinterna
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Affinity Labelling and Cloning of Steroid and Thyroid Hormone Receptors by H. Gronemeyer (Editor) (1988); ISBN: 0895735792; http://www.amazon.com/exec/obidos/ASIN/0895735792/icongroupinterna
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Alicyclic Compounds Part C: Polycarbocyclic Compounds Excluding Steroids (Rodd's Chemistry of Carbon Compounds. 2nd Edition) by S. Coffey (Editor); ISBN: 0444406816; http://www.amazon.com/exec/obidos/ASIN/0444406816/icongroupinterna
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Alicyclic Compounds Part D: Steroids (Rodd's Chemistry of Carbon Compounds. 2nd Edition) by S. Coffey (Editor); ISBN: 044440774X; http://www.amazon.com/exec/obidos/ASIN/044440774X/icongroupinterna
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Alicyclic Compounds Part E: Steroids (Cumulative Index - Vol II) (Rodd's Chemistry of Carbon Compounds. 2nd Edition) by S. Coffey (Editor); ISBN: 0444407758; http://www.amazon.com/exec/obidos/ASIN/0444407758/icongroupinterna
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Alpha-Class Glutathione Transferases As Steroid Isomerases & Scaffolds for Protein Redesign (Comprehensive Summaries of Uppsala Dissertations from the Faculty Science aNd Technology, 719) by Par L. Pettersson (2002); ISBN: 9155453279; http://www.amazon.com/exec/obidos/ASIN/9155453279/icongroupinterna
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Altered States: The Use and Abuse of Anabolic Steroids by James E. Wright, Virginia S. Cowart (Contributor) (1995); ISBN: 1570280134; http://www.amazon.com/exec/obidos/ASIN/1570280134/icongroupinterna
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An introduction to the chemistry of the terpenoids and steroids by W. Templeton; ISBN: 0408526009; http://www.amazon.com/exec/obidos/ASIN/0408526009/icongroupinterna
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Anabolic Action of Steroids and Remembrances by Charles D. Kochakian; ISBN: 9994291203; http://www.amazon.com/exec/obidos/ASIN/9994291203/icongroupinterna
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Anabolic Advantage, The Essentials Of Anabolic Steroid Use by Max Sizemore, Max Sizemore (1996); ISBN: 0966400402; http://www.amazon.com/exec/obidos/ASIN/0966400402/icongroupinterna
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Anabolic Androgenic Steroids and the Brain: Studies of Neurochemical and Behavioural Changes Using an Animal Model (Comprehensive Summaries of
Books 449
Uppsala Dissertations from the Faculty of pharmaCy, 261) by Pia Steensland (2001); ISBN: 9155451926; http://www.amazon.com/exec/obidos/ASIN/9155451926/icongroupinterna •
Anabolic Muscle Mass: The Secrets of Anabolic Reinforcement Without Steroids by Dennis B. Weis, et al; ISBN: 1552100006; http://www.amazon.com/exec/obidos/ASIN/1552100006/icongroupinterna
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Anabolic Outlaw : "I was a drug dealing, pot smoking, cocaine snorting, pill popping, acid dropping, whiskey drinking, steroid shooting bodybuilder!" by Dennis L. Bates (2001); ISBN: 096719587X; http://www.amazon.com/exec/obidos/ASIN/096719587X/icongroupinterna
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Anabolic Steroid Abuse by Geraline C. Lin (Editor), Lynda Erinoff (Editor) (1996); ISBN: 0788129694; http://www.amazon.com/exec/obidos/ASIN/0788129694/icongroupinterna
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Anabolic Steroid Abuse; ISBN: 0160284228; http://www.amazon.com/exec/obidos/ASIN/0160284228/icongroupinterna
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Anabolic Steroid Use Among High School Students (1990); ISBN: 9991288589; http://www.amazon.com/exec/obidos/ASIN/9991288589/icongroupinterna
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Anabolic Steroids and Sports by James E. Wright (1982); ISBN: 0960930604; http://www.amazon.com/exec/obidos/ASIN/0960930604/icongroupinterna
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Anabolic steroids and sports : a comprehensive, up-to-date summary and discussion of the scientific findings about the controversial drugs widely used to increase muscle size and strength by James Edward Wright; ISBN: 089626002X; http://www.amazon.com/exec/obidos/ASIN/089626002X/icongroupinterna
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Anabolic Steroids and Sports and Drug Testing: 1991-1997: An Annotated Bibliography by Ellen R. Paterson (Compiler) (1998); ISBN: 0878754997; http://www.amazon.com/exec/obidos/ASIN/0878754997/icongroupinterna
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Anabolic Steroids and Sports: A Selective Bibliography with Annotations by Ellen R. Paterson (Compiler) (1991); ISBN: 0878753893; http://www.amazon.com/exec/obidos/ASIN/0878753893/icongroupinterna
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Anabolic Steroids and the Athlete by William N. Taylor; ISBN: 0786411287; http://www.amazon.com/exec/obidos/ASIN/0786411287/icongroupinterna
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Anabolic Steroids in Sport and Exercise by Charles E. Yesalis (Editor); ISBN: 0873224019; http://www.amazon.com/exec/obidos/ASIN/0873224019/icongroupinterna
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Anabolic Steroids: Altered States by James E. Wright, Virginia S. Cowart; ISBN: 1884125034; http://www.amazon.com/exec/obidos/ASIN/1884125034/icongroupinterna
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Anabolic Steroids: And Other Performance Enhancing Drugs by Patrick Lenehan, Pat Lenehan (2003); ISBN: 041528029X; http://www.amazon.com/exec/obidos/ASIN/041528029X/icongroupinterna
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Anabolic-Androgenic Steroids by C. D. Kochakian (Editor) (1977); ISBN: 0387077103; http://www.amazon.com/exec/obidos/ASIN/0387077103/icongroupinterna
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Anabolics 2000 : Anabolic Steroid Reference Manual by William Llewellyn; ISBN: 0967930405; http://www.amazon.com/exec/obidos/ASIN/0967930405/icongroupinterna
450 Steroids
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Analysis of Steroid Hormone Drugs by S. Gorog, G.Y. Szasz; ISBN: 0444998055; http://www.amazon.com/exec/obidos/ASIN/0444998055/icongroupinterna
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Analysis of Sterols and Other Biologically Significant Steroids by W. David Nes, Edward J. Parish (Editor); ISBN: 0125154453; http://www.amazon.com/exec/obidos/ASIN/0125154453/icongroupinterna
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Analytical Profiles of Anabolic Steroids; ISBN: 9991083723; http://www.amazon.com/exec/obidos/ASIN/9991083723/icongroupinterna
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Anti-Inflammatory Steroid Action: Basic and Clinical Aspects by Robert P. Schleimer, et al; ISBN: 0126251452; http://www.amazon.com/exec/obidos/ASIN/0126251452/icongroupinterna
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Antitumor Steroids by Robert T. Blickenstaff (Editor); ISBN: 0121059529; http://www.amazon.com/exec/obidos/ASIN/0121059529/icongroupinterna
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Ashgate Handbook of Endocrine Agents and Steroids by George W. A. Milne (Editor) (2000); ISBN: 0566083833; http://www.amazon.com/exec/obidos/ASIN/0566083833/icongroupinterna
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Atlas of Steroid Structure by Jane F. Griffin (Editor), et al; ISBN: 0306661020; http://www.amazon.com/exec/obidos/ASIN/0306661020/icongroupinterna
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Bedeutung und Problematik der Steroidchemie und -biologie : ein Kapitel aus der modernen Biochemie by Friedmund Neumann; ISBN: 3486398814; http://www.amazon.com/exec/obidos/ASIN/3486398814/icongroupinterna
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Bestimmung von Steroidhormonen beim weiblichen Rind : Entwicklung von Messverfahren u. physiolog. Daten by Bernd Hoffmann; ISBN: 3489686160; http://www.amazon.com/exec/obidos/ASIN/3489686160/icongroupinterna
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Biochemistry of Steroid Hormones by H. L. J. Makin (Editor); ISBN: 0632009861; http://www.amazon.com/exec/obidos/ASIN/0632009861/icongroupinterna
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Biochemistry of steroids and other isopentenoids by William R. Nes; ISBN: 0839111274; http://www.amazon.com/exec/obidos/ASIN/0839111274/icongroupinterna
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Biology of Cholesterol and Related Steroids (910P) by N.B. Myant; ISBN: 0433228806; http://www.amazon.com/exec/obidos/ASIN/0433228806/icongroupinterna
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BRIGGS ADV IN STEROID BIOCHEMISTRY V2; ISBN: 0120375028; http://www.amazon.com/exec/obidos/ASIN/0120375028/icongroupinterna
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BRIGGS ADV IN STEROID BIOCHEMISTRY V3; ISBN: 0120375036; http://www.amazon.com/exec/obidos/ASIN/0120375036/icongroupinterna
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BRIGGS ADV IN STEROID BIOCHEMISTRY V7; ISBN: 0120375079; http://www.amazon.com/exec/obidos/ASIN/0120375079/icongroupinterna
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Building It: Muscle Building and Steroids by Foxy Denham, Pinky Whitehead; ISBN: 0911238875; http://www.amazon.com/exec/obidos/ASIN/0911238875/icongroupinterna
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Built to Survive: A Comprehensive Guide to the Medical Use of Anabolic Steroids, Nutrition and Exercise for HIV (+) men and women by Michael Mooney, Nelson R. Vergel; ISBN: 0966223101; http://www.amazon.com/exec/obidos/ASIN/0966223101/icongroupinterna
Books 451
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Cardiovascular Disease and Steroid Hormone Contraception: A Report of a WHO Scientific Group (Technical Report Series: 877) by K. Hagenfeldt (1998); ISBN: 9241208775; http://www.amazon.com/exec/obidos/ASIN/9241208775/icongroupinterna
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Chemistry and Biochemistry of Steroids by L.J. Chinn; ISBN: 0876720033; http://www.amazon.com/exec/obidos/ASIN/0876720033/icongroupinterna
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Chemistry of the Steroids by Charles W. Shoppee; ISBN: 0306306670; http://www.amazon.com/exec/obidos/ASIN/0306306670/icongroupinterna
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Chromatography of steroids by Erich Heftmann; ISBN: 044441441X; http://www.amazon.com/exec/obidos/ASIN/044441441X/icongroupinterna
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Clinical Biochem Steroid Horm by Grant/Beastall; ISBN: 0709911254; http://www.amazon.com/exec/obidos/ASIN/0709911254/icongroupinterna
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Clinical Biochemistry of Steroid Hormones: Methods and Applications by J.K. and Beastall, G.H. Grant, G. H. Beastall (Photographer); ISBN: 0444008497; http://www.amazon.com/exec/obidos/ASIN/0444008497/icongroupinterna
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Clinical Interest of Steroid Hormone Receptors in Breast Cancer (Recent Results in Cancer Research 91) by G. Leclercq, et al; ISBN: 038713042X; http://www.amazon.com/exec/obidos/ASIN/038713042X/icongroupinterna
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Clinical use of sex steroids : based on the proceedings of the Fourth Annual Symposium on Gynecologic Endocrinology, held May 7-9, 1979 at the University of Tennessee, Memphis, Tennessee; ISBN: 0815135289; http://www.amazon.com/exec/obidos/ASIN/0815135289/icongroupinterna
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Clinically Oriented Studies (Localization of Putative Steroid Receptors, Volume 2) by Louis Pertschuk (Editor) (1985); ISBN: 0849360498; http://www.amazon.com/exec/obidos/ASIN/0849360498/icongroupinterna
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CNS Neurotransmitters and Neuromodulators: Neuroactive Steroids by T. W. Stone (Editor); ISBN: 0849376335; http://www.amazon.com/exec/obidos/ASIN/0849376335/icongroupinterna
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Colorimetric and Fluorimetric Analysis of Steroids by Jaroslav Bartos; ISBN: 0120801507; http://www.amazon.com/exec/obidos/ASIN/0120801507/icongroupinterna
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Comprehensive Natural Products Chemistry : Isoprenoids Including Carotenoids and Steroids by Derek Barton (Editor), et al; ISBN: 0080431542; http://www.amazon.com/exec/obidos/ASIN/0080431542/icongroupinterna
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Contraceptive Steroids: Pharmacology and Safety (Reproductive Biology) by A.T. Gregoire, Richard P. Blye (Editor) (1986); ISBN: 0306423936; http://www.amazon.com/exec/obidos/ASIN/0306423936/icongroupinterna
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Control of gonadal steroid secretion; ISBN: 0852242042; http://www.amazon.com/exec/obidos/ASIN/0852242042/icongroupinterna
•
CRC Handbook of Chromatography: Analysis and Characterization of Steroids by Henryk Lamparczyk; ISBN: 0849330084; http://www.amazon.com/exec/obidos/ASIN/0849330084/icongroupinterna
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CRC Handbook of Chromatography: Steroids (CRC Series in Chromatography) by Joseph, Dr. Touchstone (1986); ISBN: 0849330149; http://www.amazon.com/exec/obidos/ASIN/0849330149/icongroupinterna
452 Steroids
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Death in the Locker Room: Steroids & Sports by Bob Goldman, et al; ISBN: 0896511553; http://www.amazon.com/exec/obidos/ASIN/0896511553/icongroupinterna
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Death in the Locker Room: Steroids, Cocaine & Sports by Bob Goldman, et al; ISBN: 0895865971; http://www.amazon.com/exec/obidos/ASIN/0895865971/icongroupinterna
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Developments in Steroid Histochemistry by A. H. Et Al Baillie; ISBN: 0120735504; http://www.amazon.com/exec/obidos/ASIN/0120735504/icongroupinterna
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Dhea and Sex Steroids by F. Labrie (Editor), et al (1996); ISBN: 1898099103; http://www.amazon.com/exec/obidos/ASIN/1898099103/icongroupinterna
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Dictionary of Steroids by R. A. Hill (Editor); ISBN: 0412270609; http://www.amazon.com/exec/obidos/ASIN/0412270609/icongroupinterna
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Drugs, Steroids, and Sports (Understanding Drugs) by Janet Mohun, et al; ISBN: 0531106268; http://www.amazon.com/exec/obidos/ASIN/0531106268/icongroupinterna
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Experimental Systems (Localization of Putative Steroid Receptors, Volume 1) by Louis Pertschuk (Editor) (1985); ISBN: 084936048X; http://www.amazon.com/exec/obidos/ASIN/084936048X/icongroupinterna
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False Glory: Steelers and Steroids: The Steve Courson Story by Steve Courson, Lee R. Schreiber (Contributor); ISBN: 0681411872; http://www.amazon.com/exec/obidos/ASIN/0681411872/icongroupinterna
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Fast Facts: Steroids by Jim Parker (1996); ISBN: 0892302623; http://www.amazon.com/exec/obidos/ASIN/0892302623/icongroupinterna
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Female sex steroids : receptors and function by James H. Clark; ISBN: 0387093753; http://www.amazon.com/exec/obidos/ASIN/0387093753/icongroupinterna
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First Cancer Then Lupus: The Courageous Story of One Woman's Journey Through Illness, Chemotherapy, Steroids & Pain Control by Anne O'Connell; ISBN: 0962727423; http://www.amazon.com/exec/obidos/ASIN/0962727423/icongroupinterna
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Focus on Steroids (A Drug-Alert Book) by Katherine S. Talmadge, et al; ISBN: 0816724539; http://www.amazon.com/exec/obidos/ASIN/0816724539/icongroupinterna
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Gene Regulation by Steroid Hormones by A. K. Roy; ISBN: 0387904646; http://www.amazon.com/exec/obidos/ASIN/0387904646/icongroupinterna
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Gene Regulation by Steroid Hormones II by J.H. Clark (Editor), A. K. Roy; ISBN: 038790784X; http://www.amazon.com/exec/obidos/ASIN/038790784X/icongroupinterna
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Gene Regulation by Steroid Hormones III by J.H. Clark (Editor), A. K. Roy; ISBN: 0387964363; http://www.amazon.com/exec/obidos/ASIN/0387964363/icongroupinterna
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Gene Regulation by Steroid Hormones IV by J.H. Clark (Editor), A. K. Roy; ISBN: 0387969993; http://www.amazon.com/exec/obidos/ASIN/0387969993/icongroupinterna
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Gene Regulation by Steroid Hormones IV; ISBN: 3540969993; http://www.amazon.com/exec/obidos/ASIN/3540969993/icongroupinterna
Books 453
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Genetics of Steroid Biosynthesis and Function (Moderngenetics) by J. I. Mason (Editor), J Ian Mason (2003); ISBN: 0415278783; http://www.amazon.com/exec/obidos/ASIN/0415278783/icongroupinterna
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Gold Medal Performance Without Dangerous Steroids by Paul Yazolino, Alfred J. Garrotto; ISBN: 1885587546; http://www.amazon.com/exec/obidos/ASIN/1885587546/icongroupinterna
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Gonadal steroids and brain function : IUPS-satellite symposium, Berlin, July 10-11, 1980; ISBN: 0387106065; http://www.amazon.com/exec/obidos/ASIN/0387106065/icongroupinterna
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Guide to steroid therapy by Picton Thomas; ISBN: 0853240442; http://www.amazon.com/exec/obidos/ASIN/0853240442/icongroupinterna
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Handbook of Biochemistry: Section C Lipids Carbohydrates & Steroids, Volume l by Gerald D. Fasman (Editor); ISBN: 0878195084; http://www.amazon.com/exec/obidos/ASIN/0878195084/icongroupinterna
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Handbook of Experimental Pharmacology: Anabolic-androgenic Steroids; ISBN: 3540077103; http://www.amazon.com/exec/obidos/ASIN/3540077103/icongroupinterna
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Hormonal Factors in Fertility, Infertility and Contraception (Research on Steroids, Vol 10/International Congress Series, 580) by H. J. Van Der Molen; ISBN: 0444902589; http://www.amazon.com/exec/obidos/ASIN/0444902589/icongroupinterna
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Hormonal Manipulation of Cancer: Peptides, Growth Factors, and New (Anti Steroidal Agents) by Jam G.M. Klijn, et al (1987); ISBN: 0881673013; http://www.amazon.com/exec/obidos/ASIN/0881673013/icongroupinterna
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Hormonal Steroids by V.H.T. James, J.R. Pasqualini; ISBN: 0080319785; http://www.amazon.com/exec/obidos/ASIN/0080319785/icongroupinterna
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Hormonal steroids : proceedings of the Sixth International Congress on Hormonal Steroids, Jerusalem, Israel, 5-10 September 1982; ISBN: 008030771X; http://www.amazon.com/exec/obidos/ASIN/008030771X/icongroupinterna
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Hormonal Steroids: Proceedings of the Fifth International Congress on Hormonal Steroids, New Delhi, India, October/November 1978 by V. H. T. James (1979); ISBN: 0080237967; http://www.amazon.com/exec/obidos/ASIN/0080237967/icongroupinterna
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Hormone Chemistry: Vol.2: Steroids, Thyroid Hormones, Biogenic Amines and Prostaglandins by Wilfred Roger Butt, et al; ISBN: 0853120382; http://www.amazon.com/exec/obidos/ASIN/0853120382/icongroupinterna
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Immunocytochemistry for Steroid Receptors by Louis P. Ph.D. Pertschuk, et al; ISBN: 0849369436; http://www.amazon.com/exec/obidos/ASIN/0849369436/icongroupinterna
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Immunologic methods in steroid determination; ISBN: 0390705837; http://www.amazon.com/exec/obidos/ASIN/0390705837/icongroupinterna
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Immunology of Steroid Hormone Receptors by Shanthi Raam (1988); ISBN: 0849349834; http://www.amazon.com/exec/obidos/ASIN/0849349834/icongroupinterna
454 Steroids
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Improved Non-Steroid Anti-Inflammatory Drugs: Cox-2 Enzyme Inhibitors by John R. Vane, et al (1996); ISBN: 0792388976; http://www.amazon.com/exec/obidos/ASIN/0792388976/icongroupinterna
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Inhaled Steroids in Asthma: Optimizing Effects in the Airways (Lung Biology in Health and Disease, Vol 163) by Robert P Schleimer (Editor), et al (2002); ISBN: 0824705858; http://www.amazon.com/exec/obidos/ASIN/0824705858/icongroupinterna
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Interaction of Steroid Hormone Receptors With DNA (Ellis Horwood Health Science Series) by Mels Sluyser (Editor); ISBN: 0895733668; http://www.amazon.com/exec/obidos/ASIN/0895733668/icongroupinterna
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Introduction to steroid chemistry by James Ralph Hanson; ISBN: 0082037590; http://www.amazon.com/exec/obidos/ASIN/0082037590/icongroupinterna
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Long-Acting Steroid Contraception (Advances in Human Fertility and Reproductive Endocrinology : V. 2) by Daniel R. Mishell (Editor); ISBN: 0890049327; http://www.amazon.com/exec/obidos/ASIN/0890049327/icongroupinterna
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Macho Medicine: A History of the Anabolic Steroid Epidemic by William N. Taylor (1991); ISBN: 0899506135; http://www.amazon.com/exec/obidos/ASIN/0899506135/icongroupinterna
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Mass Spectra and GC Data of Steroids : Androgens and Estrogens by Hugh L. J. Makin (Author), et al (1999); ISBN: 3527296441; http://www.amazon.com/exec/obidos/ASIN/3527296441/icongroupinterna
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Mass Spectral Collection: Androstanes and Oestrogens and Other Steroids by Michael Spiteller (Author) (1998); ISBN: 0471440345; http://www.amazon.com/exec/obidos/ASIN/0471440345/icongroupinterna
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Mass Spectrometry of Steroids by Ze-Ev V. Zaretskii; ISBN: 0470152257; http://www.amazon.com/exec/obidos/ASIN/0470152257/icongroupinterna
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Mechanism of Steroid Hormone Regulation of Gene Transcription (Molecular Biology Intelligence Unit) by Ming-Jer, Ph.D. Tsai, Bert W., M.D. O'Malley; ISBN: 1570590931; http://www.amazon.com/exec/obidos/ASIN/1570590931/icongroupinterna
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Medicinal Chemistry of Steroids (Pharmacochemistry Library, 15) by F.J. Zeelen; ISBN: 044488727X; http://www.amazon.com/exec/obidos/ASIN/044488727X/icongroupinterna
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Memoirs of the Society for Endocrinology: Volume 10, Progress in Endocrinology, Part 2, Biochemistry and Biological Actions of Steroids and Other Hormones by K. Fotherby (Editor), et al; ISBN: 0521074975; http://www.amazon.com/exec/obidos/ASIN/0521074975/icongroupinterna
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Memoirs of the Society for Endocrinology: Volume 16, The Gas Liquid Chromatography of Steroids by J. K. Grant (Editor); ISBN: 0521049024; http://www.amazon.com/exec/obidos/ASIN/0521049024/icongroupinterna
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Metabolism of Anabolic-Androgenic Steroids by Victor A. Rogozkin, et al; ISBN: 0849364159; http://www.amazon.com/exec/obidos/ASIN/0849364159/icongroupinterna
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Metabolism of Hormonal Steroids in the Neuroendocrine Structures (Serono Symposia Publications from Raven Press Vol 13) by F. Celotti, et al; ISBN: 0890045100; http://www.amazon.com/exec/obidos/ASIN/0890045100/icongroupinterna
Books 455
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Metabolizm anabolicheskikh androgennykh steroidov by V. A. Rogozkin; ISBN: 5020257494; http://www.amazon.com/exec/obidos/ASIN/5020257494/icongroupinterna
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Methods in Enzymology: Steroids and Isoprenoids, Part A (Methods in Enzymology, Vol 110) by John H. Law, et al (1985); ISBN: 0121820106; http://www.amazon.com/exec/obidos/ASIN/0121820106/icongroupinterna
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Methods in Enzymology: Steroids and Isoprenoids, Part B by John H. Law (Editor), et al (1985); ISBN: 0121820114; http://www.amazon.com/exec/obidos/ASIN/0121820114/icongroupinterna
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Methods in Enzymology: Steroids and Terpenoids by R. B. Clayton (Editor), et al (1969); ISBN: 0121818721; http://www.amazon.com/exec/obidos/ASIN/0121818721/icongroupinterna
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Methods in steroid toxicology; report of a workshop held in Bonn, Dec. 1970; ISBN: 0876720335; http://www.amazon.com/exec/obidos/ASIN/0876720335/icongroupinterna
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Microbial Conversion of Steroids and Alkaloids by H. Lizuka; ISBN: 0387107940; http://www.amazon.com/exec/obidos/ASIN/0387107940/icongroupinterna
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Microbial Transformations of Steroids by M. Čapek; ISBN: 9061936322; http://www.amazon.com/exec/obidos/ASIN/9061936322/icongroupinterna
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Modern methods of steroid analysis by Erich Heftmann; ISBN: 0123366402; http://www.amazon.com/exec/obidos/ASIN/0123366402/icongroupinterna
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Molecular Biology of Steroid and Nuclear Hormone Receptors by Leonard P. Freedman (Editor), M. Karin (Editor) (1998); ISBN: 0817639527; http://www.amazon.com/exec/obidos/ASIN/0817639527/icongroupinterna
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Molecular biology of steroid and nuclear hormone receptors; ISBN: 3764339527; http://www.amazon.com/exec/obidos/ASIN/3764339527/icongroupinterna
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Molecular Endocrinology and Steroid Hormone Action (Progress in Clinical and Biological Research, Vol 322) by James L. Stevens (Editor), Gordon H. Sato (Editor); ISBN: 0471566829; http://www.amazon.com/exec/obidos/ASIN/0471566829/icongroupinterna
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Molecular Endocrinology of the Steroid Hormones by Dennis. Schulster, et al; ISBN: 0471765821; http://www.amazon.com/exec/obidos/ASIN/0471765821/icongroupinterna
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Molecular Mechanism of Steroid Hormone Action by Virinder K. Moudgil (Editor) (1985); ISBN: 3110101181; http://www.amazon.com/exec/obidos/ASIN/3110101181/icongroupinterna
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Molecular Mechanism of Steroid Hormone Action: Recent Advances by V.K. Moudgil (Editor) (1985); ISBN: 0899250327; http://www.amazon.com/exec/obidos/ASIN/0899250327/icongroupinterna
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Molecular Structure and Biological Activity of Steroids by Martin Bohl, William L. Duax (Editor) (1992); ISBN: 084936955X; http://www.amazon.com/exec/obidos/ASIN/084936955X/icongroupinterna
•
Multiple molecular forms of steroid hormone receptors : proceedings of the XI Acta Endocrinologica Congress satellite workshop, Lausanne, Switzerland, June 23rd, 1977;
456 Steroids
ISBN: 0444800107; http://www.amazon.com/exec/obidos/ASIN/0444800107/icongroupinterna •
Muscling in: A Chilling Tale of Teenage Suicide, Steroids, Cops, and Connections by Kelly S. Losey; ISBN: 0917665481; http://www.amazon.com/exec/obidos/ASIN/0917665481/icongroupinterna
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Need to Know: Pack B of 4: Alcohol / Tobacco / Ecstasy / Steroids (Need to Know) by Rob Alcraft; ISBN: 0431097933; http://www.amazon.com/exec/obidos/ASIN/0431097933/icongroupinterna
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Need to Know: Pack B: Alcohol / Tobacco / Ecstasy / Steroids (Need to Know) by Rob Alcraft; ISBN: 0431097836; http://www.amazon.com/exec/obidos/ASIN/0431097836/icongroupinterna
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Need to Know: Steroids (Need to Know) by Rob Alcraft; ISBN: 0431097925; http://www.amazon.com/exec/obidos/ASIN/0431097925/icongroupinterna
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Neurobiological Effects of Sex Steroid Hormones by Paul E. Micevych (Editor), Ronald P. Jr Hammer (Editor) (1995); ISBN: 0521454301; http://www.amazon.com/exec/obidos/ASIN/0521454301/icongroupinterna
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Neurobiology of Steroids (Methods in Neurosciences, Vol 22) by Ronald E. De Kloet, et al; ISBN: 012185292X; http://www.amazon.com/exec/obidos/ASIN/012185292X/icongroupinterna
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Neuroendocrinology of Sex Steroids: Basic Knowledge and Clinical Implications (New Developments in Biosciences, 6) by W.G. Rossmanith, W.A. Scherbaum (Editor) (1992); ISBN: 3110136163; http://www.amazon.com/exec/obidos/ASIN/3110136163/icongroupinterna
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Neuroplasticity, Development, and Steroid Hormone Action by Robert J. Handa (Editor), et al; ISBN: 084930962X; http://www.amazon.com/exec/obidos/ASIN/084930962X/icongroupinterna
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Neurosteroids and brain function; ISBN: 3137762014; http://www.amazon.com/exec/obidos/ASIN/3137762014/icongroupinterna
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Neurosteroids and Brain Function (Fidia Research Foundation Symposium Series, Vol. 8) by Erminio Costa, Steven M. Paul (Editor); ISBN: 0865774226; http://www.amazon.com/exec/obidos/ASIN/0865774226/icongroupinterna
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Nitric Oxide, Cytochromes P450, and Sexual Steroid Hormones (Ernst Schering Research Foundation Workshop, 21) by J. R., Jr. Lancaster (Editor), J. F. Parkinson (Editor) (1997); ISBN: 3540630503; http://www.amazon.com/exec/obidos/ASIN/3540630503/icongroupinterna
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Non-Radiometric Assays: Technology and Application in Polypeptide and Steroid Hormone Detection (Progress in Clinical and Biological Research, 285) by Florence P. Haseltine (Editor), Barry D. Albertson (Editor); ISBN: 0471501875; http://www.amazon.com/exec/obidos/ASIN/0471501875/icongroupinterna
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Non-Reproductive Actions of Sex Steroids - Symposium No. 191 by CIBA Foundation Symposium (Author) (1995); ISBN: 0471955132; http://www.amazon.com/exec/obidos/ASIN/0471955132/icongroupinterna
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Non-Stipitate Steroid Fungi in the Northeastern United States and Adjacent Canada (Mycologia Memoir, No 14) by George P. Chamuris (1989); ISBN: 344376004X; http://www.amazon.com/exec/obidos/ASIN/344376004X/icongroupinterna
Books 457
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Oral contraceptives and steroid chemistry in the People's Republic of China : a trip report of the American Steroid Chemistry and Biochemistry Delegation; ISBN: 0309026385; http://www.amazon.com/exec/obidos/ASIN/0309026385/icongroupinterna
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Organic Reactions in Steroid Chemistry by John Fried; ISBN: 9999046061; http://www.amazon.com/exec/obidos/ASIN/9999046061/icongroupinterna
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Organ-Selective Actions of Steroid Hormones (Ernst Schering Research Foundation Workshop, 16) by David T. Baird (Editor), et al; ISBN: 0387603387; http://www.amazon.com/exec/obidos/ASIN/0387603387/icongroupinterna
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Percutaneous Absorption of Steroids by Paris, International Symposium on Percutaneous Absorption of Steroids; ISBN: 0124806805; http://www.amazon.com/exec/obidos/ASIN/0124806805/icongroupinterna
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Pharmacological modulation of steroid action; ISBN: 0890043736; http://www.amazon.com/exec/obidos/ASIN/0890043736/icongroupinterna
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Pharmacology of steroid contraceptive drugs; ISBN: 0890041873; http://www.amazon.com/exec/obidos/ASIN/0890041873/icongroupinterna
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Pharmacology of the Contraceptive Steroids by Joseph W. Goldzieher (Editor), Ken Fotherby (Editor); ISBN: 0781700973; http://www.amazon.com/exec/obidos/ASIN/0781700973/icongroupinterna
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Photochemistry and spectroscopy of some steroidal gb s, gc s-unsaturated ketones : a geometry-photoreactivity study by Reinier van Nispen; ISBN: 9090049274; http://www.amazon.com/exec/obidos/ASIN/9090049274/icongroupinterna
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Proceedings of the fourth international Congress on Hormonal Steroids, Mexico City, September 1974; ISBN: 0080196829; http://www.amazon.com/exec/obidos/ASIN/0080196829/icongroupinterna
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Proceedings of the Fourth International Symposium of the Journal of Steroid Biochemistry, Paris, 28-30 May 1979; ISBN: 0080259014; http://www.amazon.com/exec/obidos/ASIN/0080259014/icongroupinterna
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Proceedings of the third International Symposium of the Journal of Steroid Biochemistry, Helsinki, 7-9 June 1976; ISBN: 0080213073; http://www.amazon.com/exec/obidos/ASIN/0080213073/icongroupinterna
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Proteins and Steroids in Early Pregnancy by Beier; ISBN: 0387104577; http://www.amazon.com/exec/obidos/ASIN/0387104577/icongroupinterna
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Protooncogenes and Growth Factors in Steroid Hormone Induced Growth and Differentiation by Sohaib A., Ph.D. Khan, George M., Ph.D. Stancel (Editor); ISBN: 0849386721; http://www.amazon.com/exec/obidos/ASIN/0849386721/icongroupinterna
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Quantitative Analysis of Steroids by S. Gorog; ISBN: 0444996982; http://www.amazon.com/exec/obidos/ASIN/0444996982/icongroupinterna
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Radioimmunoassay of steroid hormones; ISBN: 3527256466; http://www.amazon.com/exec/obidos/ASIN/3527256466/icongroupinterna
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Recent Advances in Steroid Hormone Action by V.K. Moudigil (Editor); ISBN: 089925313X; http://www.amazon.com/exec/obidos/ASIN/089925313X/icongroupinterna
458 Steroids
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Recent progress in reproductive endocrinology : a Conference on Gonadotrophins and Gonadal Steroids held in Milan, May 24-26, 1973; ISBN: 0121983609; http://www.amazon.com/exec/obidos/ASIN/0121983609/icongroupinterna
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Recent results in peptide hormone and androgenic steroid research : proceedings of the 9th congress of the Hungarian Society of Endocrinology and Metabolism Szeged, Hungary, July 2-4, 1979; ISBN: 9630522926; http://www.amazon.com/exec/obidos/ASIN/9630522926/icongroupinterna
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Receptor Medicated Antisteroid Action by M.K. Agarwal (Editor) (1988); ISBN: 0899253741; http://www.amazon.com/exec/obidos/ASIN/0899253741/icongroupinterna
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Receptor Medicated Antisteroid Action (1988); ISBN: 3110113554; http://www.amazon.com/exec/obidos/ASIN/3110113554/icongroupinterna
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Receptor Purification: Receptors for Steroid Hormones, Thyroid Hormones, and Others by Gerald Litwack (Editor); ISBN: 0896031837; http://www.amazon.com/exec/obidos/ASIN/0896031837/icongroupinterna
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Receptors and mechanism of action of steroid hormones; ISBN: 0824764390; http://www.amazon.com/exec/obidos/ASIN/0824764390/icongroupinterna
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Research on Steroids (Proceedings of the Serono Symposia) by International Study Group for Steroid Hormones; ISBN: 0124160506; http://www.amazon.com/exec/obidos/ASIN/0124160506/icongroupinterna
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Safety Requirements for Contraceptive Steroids by Frank Michal (Editor); ISBN: 0521354595; http://www.amazon.com/exec/obidos/ASIN/0521354595/icongroupinterna
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Schering Symposium on Biodynamics and Mechanism of Action of Steroid Hormones, Berlin 1968 by Schering Symposium on Biodynamics and Mechanism of Action of Steroid H, et al; ISBN: 0080069428; http://www.amazon.com/exec/obidos/ASIN/0080069428/icongroupinterna
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Schering Workshop on Steroid Hormone "Receptors," Berlin, December 7 to 9, 1970; ISBN: 0080175783; http://www.amazon.com/exec/obidos/ASIN/0080175783/icongroupinterna
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Schering Workshop on Steroid Metabolism: "in vitro versus in vivo."; ISBN: 0080175449; http://www.amazon.com/exec/obidos/ASIN/0080175449/icongroupinterna
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Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds : Alicyclic Compounds : Part B: Six- and Higher-membered Monocarbocyclic Compounds (Partial: Chapters 6-8 in this Volume). Part C: Polycarbocyclic Compounds excluding Steroids. Parts D and E: Steroids by Malcolm Sainsbury (Editor); ISBN: 0444814833; http://www.amazon.com/exec/obidos/ASIN/0444814833/icongroupinterna
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Sex Steroids and Bone (Ernst Schering Research Foundation Workshop; 9) by R. Ziegler, J. Pfeilschifter; ISBN: 3540573747; http://www.amazon.com/exec/obidos/ASIN/3540573747/icongroupinterna
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Sex steroids and the cardiovascular system; ISBN: 3540557288; http://www.amazon.com/exec/obidos/ASIN/3540557288/icongroupinterna
Books 459
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Sex Steroids and the Cardiovascular System (Schering Foundation Workshop, Vol 5) by P. Ramwell, et al; ISBN: 0387557288; http://www.amazon.com/exec/obidos/ASIN/0387557288/icongroupinterna
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Sex Steroids and the Cardiovascular System: The Proceedings of the 1st Interdisciplinary Workshop, Tuebingen, Germany by T.H. Lippert (Editor), et al; ISBN: 1850709564; http://www.amazon.com/exec/obidos/ASIN/1850709564/icongroupinterna
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Sex-Steroid Interactions With Growth Hormone (Serono Symposia USA) by Johannes D. Veldhuis (Editor), Andrea Giustina (Editor) (1999); ISBN: 0387988106; http://www.amazon.com/exec/obidos/ASIN/0387988106/icongroupinterna
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Should Steroids Be Banned from Sports (Opposing Viewpoints Pamphlets); ISBN: 1565101960; http://www.amazon.com/exec/obidos/ASIN/1565101960/icongroupinterna
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Some implications of steroid hormones in cancer: the Marie Curie Memorial Foundation workshop conference at the University of Surrey, Guildford, 8th May,1970; ISBN: 0433363800; http://www.amazon.com/exec/obidos/ASIN/0433363800/icongroupinterna
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Spectral Data for Steroids (Trc Data Series) by Michael Frenkel, K.N., Eds. Marsh (1994); ISBN: 1883400007; http://www.amazon.com/exec/obidos/ASIN/1883400007/icongroupinterna
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Sports and Anabolic Steroids: Index of Modern Information by Hugo H. Bronsen (1988); ISBN: 0881649244; http://www.amazon.com/exec/obidos/ASIN/0881649244/icongroupinterna
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Steroid Action on Brain and Behavior: Tenth Annual Karger Workshop Los Angeles, Calif., November 6-7, 1998 (Brain, Behavior and Evolution, Volume 54, Number 1, 1999) by Joseph G. Dulka (Editor) (1999); ISBN: 3805569696; http://www.amazon.com/exec/obidos/ASIN/3805569696/icongroupinterna
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Steroid Analysis by H. L. J. Makin (Editor), et al (1995); ISBN: 0751401285; http://www.amazon.com/exec/obidos/ASIN/0751401285/icongroupinterna
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Steroid Analysis by Hplc: Recent Applications (Chromatographic Science) by M. Kautsky (1981); ISBN: 0824713249; http://www.amazon.com/exec/obidos/ASIN/0824713249/icongroupinterna
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Steroid Analysis in the Pharmaceutical Industry; ISBN: 0470211784; http://www.amazon.com/exec/obidos/ASIN/0470211784/icongroupinterna
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Steroid analysis in the pharmaceutical industry : hormonal steroids, sterols, vitamins D, cardiac glycosides; ISBN: 0745800998; http://www.amazon.com/exec/obidos/ASIN/0745800998/icongroupinterna
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Steroid Analysis in the Pharmaceutical Industry: Hormonal Steroids, Sterols, Vitamins D, Cardiac Glycosides (Ellis Horwood Series in Analytical Chem) by S. Gorog (Editor); ISBN: 0138471533; http://www.amazon.com/exec/obidos/ASIN/0138471533/icongroupinterna
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Steroid and Sterol Hormone Action by T.C. Spelsberg, R. Kumar (Editor) (1987); ISBN: 0898388945; http://www.amazon.com/exec/obidos/ASIN/0898388945/icongroupinterna
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Steroid biochemistry; ISBN: 0849351944; http://www.amazon.com/exec/obidos/ASIN/0849351944/icongroupinterna
460 Steroids
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Steroid biochemistry and pharmacology by Michael H. Briggs; ISBN: 0121346501; http://www.amazon.com/exec/obidos/ASIN/0121346501/icongroupinterna
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Steroid Blues by Richard La Plante; ISBN: 0751515655; http://www.amazon.com/exec/obidos/ASIN/0751515655/icongroupinterna
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Steroid Contraceptives and Women's Response: Regional Variability in Side-Effects and Pharmacokinetics (Reproductive Biology) by Rachel Snow, Peter Hall (Editor) (1994); ISBN: 0306447185; http://www.amazon.com/exec/obidos/ASIN/0306447185/icongroupinterna
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Steroid Converting Enzymes and Diseases by K. Fotherby, S.B. Pal (Editor) (1984); ISBN: 3110095564; http://www.amazon.com/exec/obidos/ASIN/3110095564/icongroupinterna
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Steroid Drug Dangers (Drug Dangers) by Judy Monroe; ISBN: 0766011542; http://www.amazon.com/exec/obidos/ASIN/0766011542/icongroupinterna
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Steroid Drug Response Metaboli by Kourounakis Re; ISBN: 0138475598; http://www.amazon.com/exec/obidos/ASIN/0138475598/icongroupinterna
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Steroid Formation Degradation and Action in Peripheral Tissues (Annals of the New York Academy of Sciences, Vol 595) by L. Castagnetta, et al; ISBN: 0897665651; http://www.amazon.com/exec/obidos/ASIN/0897665651/icongroupinterna
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Steroid Hormone Action (Frontiers in Molecular Biology) by Malcolm G. Parker (Editor); ISBN: 0199633932; http://www.amazon.com/exec/obidos/ASIN/0199633932/icongroupinterna
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Steroid Hormone Action (UCLA Symposia on Cellular and Molecular Biology, New Series, Vol 75) by Gordon Ringold (Editor); ISBN: 0471612669; http://www.amazon.com/exec/obidos/ASIN/0471612669/icongroupinterna
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Steroid hormone action and cancer; ISBN: 0306340046; http://www.amazon.com/exec/obidos/ASIN/0306340046/icongroupinterna
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Steroid Hormone and Regulation of the Brain: Proceedings of the International Symposium Held at Stock Holm, Sweden, October 27-28, 1980 by Kjell Fuxe (1981); ISBN: 0080268641; http://www.amazon.com/exec/obidos/ASIN/0080268641/icongroupinterna
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Steroid hormone receptor systems : [proceedings]; ISBN: 0306401827; http://www.amazon.com/exec/obidos/ASIN/0306401827/icongroupinterna
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Steroid Hormone Receptors: Basic and Clinical Aspects (Hormones in Health and Disease) by V. K. Moudgil (Editor) (1994); ISBN: 0817636943; http://www.amazon.com/exec/obidos/ASIN/0817636943/icongroupinterna
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Steroid Hormone Receptors: Structure and Function by Hakan and Gustafsson, JanAke Eriksson (Editor) (1984); ISBN: 0444805591; http://www.amazon.com/exec/obidos/ASIN/0444805591/icongroupinterna
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Steroid Hormone Receptors: Their Intracellular Localization (Ellis Horwood Series in Biomedicine) by C. R. Clark (Editor); ISBN: 0895734982; http://www.amazon.com/exec/obidos/ASIN/0895734982/icongroupinterna
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Steroid Hormone Resistance: Mechanisms and Clinical Aspects (Advances in Experimental Medicine and Biology, 196) by Georpe P. Chrousos, et al; ISBN: 0306422298; http://www.amazon.com/exec/obidos/ASIN/0306422298/icongroupinterna
Books 461
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Steroid Hormones by D.B. Gower; ISBN: 0815138326; http://www.amazon.com/exec/obidos/ASIN/0815138326/icongroupinterna
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Steroid Hormones by B. Green (Editor), R. E. Leake (Editor); ISBN: 0947946659; http://www.amazon.com/exec/obidos/ASIN/0947946659/icongroupinterna
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Steroid hormones and brain function by Charles H. Sawyer, Roger A. Gorski; ISBN: 0520018877; http://www.amazon.com/exec/obidos/ASIN/0520018877/icongroupinterna
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Steroid Hormones and Cell Cycle Regulation by Kerry L. Burnstein (Editor) (2002); ISBN: 1402070489; http://www.amazon.com/exec/obidos/ASIN/1402070489/icongroupinterna
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Steroid hormones and metabolism by Kenneth W. McKerns; ISBN: 0390622982; http://www.amazon.com/exec/obidos/ASIN/0390622982/icongroupinterna
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Steroid Hormones and the T-Cell Cytokine Profile by G. A. W. Rook (Editor), S. Lightman (Editor); ISBN: 3540760571; http://www.amazon.com/exec/obidos/ASIN/3540760571/icongroupinterna
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Steroid Hormones and Uterine Bleeding (Aaas Publication; 92-43s) by Nancy J. Alexander, Catherine D'Arcangues (Editor); ISBN: 0871685086; http://www.amazon.com/exec/obidos/ASIN/0871685086/icongroupinterna
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Steroid Hormones in Saliva (Frontiers of Oral Physiology, Vol. 5) by D. B. Ferguson (Editor) (1984); ISBN: 3805538480; http://www.amazon.com/exec/obidos/ASIN/3805538480/icongroupinterna
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Steroid Hormones: Volume 1 by Benjamin S. Leung; ISBN: 0852006217; http://www.amazon.com/exec/obidos/ASIN/0852006217/icongroupinterna
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Steroid immunoassay : proceedings of the fifth Tenovus Workshop, Cardiff, April 1974; ISBN: 0900663057; http://www.amazon.com/exec/obidos/ASIN/0900663057/icongroupinterna
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Steroid induced uterine proteins : proceedings of the International Symposium on Steroid Induced Uterine Proteins held in Marburg, West Germany, 28-29 September, 1979; ISBN: 0444802037; http://www.amazon.com/exec/obidos/ASIN/0444802037/icongroupinterna
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Steroid Microbiology by Pinhas Z. Margalith; ISBN: 0398051879; http://www.amazon.com/exec/obidos/ASIN/0398051879/icongroupinterna
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Steroid Modulation of Neuroendocrine Function Sterols, Steroids and Bone Metabolism: Proceedings of the XI Meeting of the International Study Group for Steroid Hormones, Rome, November 30-December 2, 1983 (Research on Steroids) by Ita International Study Group for Steroid Hormones Meeting 1983 Rome, et al (1985); ISBN: 044480594X; http://www.amazon.com/exec/obidos/ASIN/044480594X/icongroupinterna
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Steroid reaction mechanisms by D. N. Kirk; ISBN: 0444406824; http://www.amazon.com/exec/obidos/ASIN/0444406824/icongroupinterna
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Steroid Receptor Methods: Protocols and Assays by Benjamin A. Lieberman (Editor); ISBN: 0896037541; http://www.amazon.com/exec/obidos/ASIN/0896037541/icongroupinterna
462 Steroids
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Steroid Receptors and Antihormones (Annals of the New York Academy of Sciences, Volume 761) by David Henderson (Editor), Daniel Philibert; ISBN: 0897669371; http://www.amazon.com/exec/obidos/ASIN/0897669371/icongroupinterna
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Steroid Receptors and Disease: Cancer, Autoimmune, Bone, and Circulatory Disorders by Peter J. Sheridan, et al; ISBN: 0824779541; http://www.amazon.com/exec/obidos/ASIN/0824779541/icongroupinterna
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Steroid receptors and hormone-dependent neoplasia; ISBN: 0893520438; http://www.amazon.com/exec/obidos/ASIN/0893520438/icongroupinterna
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Steroid receptors and the management of cancer; ISBN: 0849354773; http://www.amazon.com/exec/obidos/ASIN/0849354773/icongroupinterna
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Steroid Receptors in Health and Disease (Serano Symposia, USA) by Virinder K. Moudgil (Editor); ISBN: 030642987X; http://www.amazon.com/exec/obidos/ASIN/030642987X/icongroupinterna
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Steroid Receptors in the Management of Cancer by Thompson, Lippa; ISBN: 0849354781; http://www.amazon.com/exec/obidos/ASIN/0849354781/icongroupinterna
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Steroid Therapy by Daniel L. Azarnoff; ISBN: 0721614698; http://www.amazon.com/exec/obidos/ASIN/0721614698/icongroupinterna
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Steroid-cell interactions by R. J. B. King; ISBN: 0839106785; http://www.amazon.com/exec/obidos/ASIN/0839106785/icongroupinterna
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Steroidhormone : Biosynthese, Stoffwechsel, Wirkung by Lothar Träger; ISBN: 0387080120; http://www.amazon.com/exec/obidos/ASIN/0387080120/icongroupinterna
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Steroid-Hormone-Dependent Organization of Neuroendocrine Functions (Neuroscience Intelligence Unit) by Vladimir Patchev, Osborne F. X. Almeida; ISBN: 1570595550; http://www.amazon.com/exec/obidos/ASIN/1570595550/icongroupinterna
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Steroid-protein interactions by U. Westphal; ISBN: 0387053123; http://www.amazon.com/exec/obidos/ASIN/0387053123/icongroupinterna
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Steroid-protein interactions : basic and clinical aspects; ISBN: 0897664736; http://www.amazon.com/exec/obidos/ASIN/0897664736/icongroupinterna
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Steroid-Protein Interactions II (Monographs on Endocrinology, Vol 27) by U.F. Westphal (1986); ISBN: 0387153217; http://www.amazon.com/exec/obidos/ASIN/0387153217/icongroupinterna
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Steroid-Protein Interactions: Basic and Clinical Aspects: Second International Symposium on Binding Proteins (Annals of the New York Academy of Sci) by Roberto Frairia, et al (1988); ISBN: 0897664728; http://www.amazon.com/exec/obidos/ASIN/0897664728/icongroupinterna
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Steroids by William Francis Johns; ISBN: 0408706201; http://www.amazon.com/exec/obidos/ASIN/0408706201/icongroupinterna
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Steroids by Albert Booher; ISBN: 0561040141; http://www.amazon.com/exec/obidos/ASIN/0561040141/icongroupinterna
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Steroids (Drug Abuse Prevention Library) by Lawrence Clayton; ISBN: 0823920631; http://www.amazon.com/exec/obidos/ASIN/0823920631/icongroupinterna
Books 463
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Steroids (Drug Education Library) by Lucent Books (2005); ISBN: 1560069171; http://www.amazon.com/exec/obidos/ASIN/1560069171/icongroupinterna
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Steroids (Drug Library) by Scott E., Ph.D. Lukas; ISBN: 089490471X; http://www.amazon.com/exec/obidos/ASIN/089490471X/icongroupinterna
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Steroids (Facts About Series) by Sarah Stevens; ISBN: 0896866068; http://www.amazon.com/exec/obidos/ASIN/0896866068/icongroupinterna
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Steroids (Health Issues) by Karla Fitzhugh; ISBN: 0739864262; http://www.amazon.com/exec/obidos/ASIN/0739864262/icongroupinterna
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Steroids (Impact Book) by Hank Nuwer; ISBN: 0531109461; http://www.amazon.com/exec/obidos/ASIN/0531109461/icongroupinterna
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Steroids (Junior Drug Awareness) by Dynise Balcavage, et al; ISBN: 079105179X; http://www.amazon.com/exec/obidos/ASIN/079105179X/icongroupinterna
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Steroids (Just the Facts) by Sean Connolly; ISBN: 1575722593; http://www.amazon.com/exec/obidos/ASIN/1575722593/icongroupinterna
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Steroids 101 by Jeff Summers; ISBN: 0972103902; http://www.amazon.com/exec/obidos/ASIN/0972103902/icongroupinterna
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Steroids and Endometrial Cancer: Progress in Cancer Research and Therapy by Valerio Maria; Nenci, Italo and Flamigni, Carlo Jasonni (Editor) (1984); ISBN: 0890048347; http://www.amazon.com/exec/obidos/ASIN/0890048347/icongroupinterna
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Steroids and Neuronal Activity - Symposium No. 153 by CIBA Foundation Symposium (Author); ISBN: 0471926892; http://www.amazon.com/exec/obidos/ASIN/0471926892/icongroupinterna
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Steroids and Peptides: Selected Chemical Aspects for Biology, Biochemistry, and Medicine by Joseph B. Dence; ISBN: 0471047007; http://www.amazon.com/exec/obidos/ASIN/0471047007/icongroupinterna
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Steroids and their mechanism of action in nonmammalian vertebrates; ISBN: 0890044872; http://www.amazon.com/exec/obidos/ASIN/0890044872/icongroupinterna
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Steroids and Your Muscles: The Incredibly Disgusting Story (Incredibly Disgusting Drugs) by Albert Spring; ISBN: 0823933938; http://www.amazon.com/exec/obidos/ASIN/0823933938/icongroupinterna
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Steroids for Strength (150031 Grades 7-8) (1989); ISBN: 0883097214; http://www.amazon.com/exec/obidos/ASIN/0883097214/icongroupinterna
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Steroids for Strength/150131 (1989); ISBN: 088309746X; http://www.amazon.com/exec/obidos/ASIN/088309746X/icongroupinterna
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Steroids in Asthma: A Reappraisal in Light of Inhalation Therapy by T.J.H. Clark (Editor) (1983); ISBN: 086471002X; http://www.amazon.com/exec/obidos/ASIN/086471002X/icongroupinterna
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Steroids in Diseases of the Central Nervous System by Rudy Capildeo (Editor); ISBN: 0471919594; http://www.amazon.com/exec/obidos/ASIN/0471919594/icongroupinterna
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Steroids in nonmammalian vertebrates by D. R. Idler; ISBN: 0123703506; http://www.amazon.com/exec/obidos/ASIN/0123703506/icongroupinterna
464 Steroids
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Steroids Made It Possible (Profiles, Pathways, and Dreams: Autobiographies of Eminent Chemists) by Carl Djerassi (1990); ISBN: 0841217734; http://www.amazon.com/exec/obidos/ASIN/0841217734/icongroupinterna
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Steroids, Thyroid Hormones, Biogenic Amines and Prostaglandins (Hormone Chemistry) by Wilfrid R. Butt; ISBN: 0470989610; http://www.amazon.com/exec/obidos/ASIN/0470989610/icongroupinterna
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Steroids: Big Muscles, Big Problems (Issues in Focus Series) by Alvin Silverstein, et al; ISBN: 0894903187; http://www.amazon.com/exec/obidos/ASIN/0894903187/icongroupinterna
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Steroids: Dangerous Game by Lisa Angowski Rogak, Lisa Angowski Rogak Shaw; ISBN: 0822500485; http://www.amazon.com/exec/obidos/ASIN/0822500485/icongroupinterna
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Steroids: Keys to Life by Rupert, Witzmann; ISBN: 0442295901; http://www.amazon.com/exec/obidos/ASIN/0442295901/icongroupinterna
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Steroids: principles and techniques by D. Kilshaw; ISBN: 0407772707; http://www.amazon.com/exec/obidos/ASIN/0407772707/icongroupinterna
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Steroidy morskikh organizmov by G. B. Eliakov; ISBN: 502003956X; http://www.amazon.com/exec/obidos/ASIN/502003956X/icongroupinterna
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Struktur und Absorptionsspektroskopie der Steroide und Alkaloide by Manfred Kraft; ISBN: 3135143015; http://www.amazon.com/exec/obidos/ASIN/3135143015/icongroupinterna
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Terpenoids and Steroids by J. R. Hanson (Editor) (1979); ISBN: 0851866506; http://www.amazon.com/exec/obidos/ASIN/0851866506/icongroupinterna
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Terpenoids and Steroids (Specialist Periodical Reports) by Karl Howard Overton (Editor); ISBN: 085186256X; http://www.amazon.com/exec/obidos/ASIN/085186256X/icongroupinterna
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Terpenoids and Steroids: A Review of the Literature Published Between Sept. 1980 and Aug. 1981 by J.R. Hanson (Editor) (1983); ISBN: 0851863566; http://www.amazon.com/exec/obidos/ASIN/0851863566/icongroupinterna
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Terpenoids and Steroids: Volume 2 (Specialist Periodical Reports) by Karl Howard Overton (Editor); ISBN: 0851862667; http://www.amazon.com/exec/obidos/ASIN/0851862667/icongroupinterna
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Terpenoids and Steroids: Volume 3 (Specialist Periodical Reports) by Karl Howard Overton (Editor); ISBN: 0851862764; http://www.amazon.com/exec/obidos/ASIN/0851862764/icongroupinterna
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Terpenoids and Steroids: Volume 4 (Specialist Periodical Reports) by Karl Howard Overton (Editor); ISBN: 0851862861; http://www.amazon.com/exec/obidos/ASIN/0851862861/icongroupinterna
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Terpenoids and Steroids: Volume 5 (Specialist Periodical Reports) by Karl Howard Overton (Editor); ISBN: 0851862969; http://www.amazon.com/exec/obidos/ASIN/0851862969/icongroupinterna
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Terpenoids and Steroids: Volume 6 (Specialist Periodical Reports) by Karl Howard Overton (Editor); ISBN: 085186306X; http://www.amazon.com/exec/obidos/ASIN/085186306X/icongroupinterna
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The Antiprogestin Steroid Ru 486 and Human Fertility Control (Reproductive Biology) by Etienne-Emile Baulieu, Sheldon J. Segal (Editor); ISBN: 0306421038; http://www.amazon.com/exec/obidos/ASIN/0306421038/icongroupinterna
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The Brain: Source and Target for Sex Steroid Hormones, 1st Tuscania Conference on Reproductive Medicine by A. R. Genazzani (Editor), et al; ISBN: 1850707731; http://www.amazon.com/exec/obidos/ASIN/1850707731/icongroupinterna
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The Development of Responsiveness to Steroid Hormones by Alvin M. Kaye (Editor), et al; ISBN: 008024940X; http://www.amazon.com/exec/obidos/ASIN/008024940X/icongroupinterna
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The evaluation of testicular endocrine function before and in puberty; effects of a single dose of human chorionic gonadotropin on urinary steroid excretion under normal and pathological conditions by Milo Zachmann; ISBN: 8774940503; http://www.amazon.com/exec/obidos/ASIN/8774940503/icongroupinterna
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The Identities of Membrane Steroid Receptors:.And Other Proteins Mediating Nongenomic Steroid Action by Cheryl S. Watson (Editor) (2003); ISBN: 1402073445; http://www.amazon.com/exec/obidos/ASIN/1402073445/icongroupinterna
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The New Biology of Steroid Hormones (Serono Symposia Publications from Raven Press, Vol 74) by R.B. Hochber, et al (1991); ISBN: 0881676535; http://www.amazon.com/exec/obidos/ASIN/0881676535/icongroupinterna
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The Official Patient's Sourcebook on Anabolic Steroid Dependence: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597832617; http://www.amazon.com/exec/obidos/ASIN/0597832617/icongroupinterna
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The Practical Use of Anabolic Steroids With Athletes by Robert Kerr (1982); ISBN: 9996739139; http://www.amazon.com/exec/obidos/ASIN/9996739139/icongroupinterna
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The Sex steroids; molecular mechanisms; ISBN: 0390622974; http://www.amazon.com/exec/obidos/ASIN/0390622974/icongroupinterna
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The Steroid Bible by Steve Gallaway (1997); ISBN: 1890342009; http://www.amazon.com/exec/obidos/ASIN/1890342009/icongroupinterna
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The Steroid Caper by Doctor "G" (2002); ISBN: 1403335117; http://www.amazon.com/exec/obidos/ASIN/1403335117/icongroupinterna
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The steroid/thyroid hormone receptor family and gene regulation : proceedings of the 2nd International CBT Symposium, Stockholm, Sweden, November 4-5, 1988; ISBN: 3764322756; http://www.amazon.com/exec/obidos/ASIN/3764322756/icongroupinterna
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The Steroid/Thyroid Hormone Receptor Family and Gene Regulation: Proceedings of the 2nd International Cbt Symposium Stockholm, Sweden, November 4-5, (Birkhauser Congress Reports. Life Sciences, Vol. 4) by Sweden)/ Eriksson, H./ Gustafsson, J.A. International Cbt Symposium 1988 Stockholm (Editor) (1989); ISBN: 0817622756; http://www.amazon.com/exec/obidos/ASIN/0817622756/icongroupinterna
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The Steroids Game by Charles E. Yesalis, Virginia S. Cowart (1998); ISBN: 0880114940; http://www.amazon.com/exec/obidos/ASIN/0880114940/icongroupinterna
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Topical Steroid Treatment for Asthma and Rhinitis by Mygind, Clark; ISBN: 0702007854; http://www.amazon.com/exec/obidos/ASIN/0702007854/icongroupinterna
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Topical Steroid Treatment for Asthma and Rhinitis (1980); ISBN: 0028587006; http://www.amazon.com/exec/obidos/ASIN/0028587006/icongroupinterna
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Topical Steroids for Skin Disorders by Michele Clement, Anthony Du Vuvuer; ISBN: 0632013443; http://www.amazon.com/exec/obidos/ASIN/0632013443/icongroupinterna
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Total steroid synthesis by A. A. Akhrem; ISBN: 0306303809; http://www.amazon.com/exec/obidos/ASIN/0306303809/icongroupinterna
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Total synthesis of steroids by Robert T. Blickenstaff; ISBN: 0121059502; http://www.amazon.com/exec/obidos/ASIN/0121059502/icongroupinterna
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Vitamin D : chemistry, biology and clinical applications of the steroid hormone : proceedings of the Tenth Workshop on Vitamin D, Strasbourg, France, May 24-29, 1997 by Roger Bouillon, A. W. Norman; ISBN: 1891168002; http://www.amazon.com/exec/obidos/ASIN/1891168002/icongroupinterna
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Vitamin D: A Pluripotent Steroid Hormone: Structional Studies, Molecular Endocrinology and Clinical Applications: Proceedings of the Ninth Workshop on Vitamin by A. W. Norman (Editor), et al (1995); ISBN: 3110141574; http://www.amazon.com/exec/obidos/ASIN/3110141574/icongroupinterna
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Vitamin D: The Calcium Homeostatic Steroid Hormone by Anthony W. Norman; ISBN: 0125210507; http://www.amazon.com/exec/obidos/ASIN/0125210507/icongroupinterna
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Vitamins and Hormones: Advances in Research and Applications: Steroids by Gerald Litwack (Editor) (1995); ISBN: 0127098496; http://www.amazon.com/exec/obidos/ASIN/0127098496/icongroupinterna
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Voltaren : a new, non-steroid antirheumatic agent (diclofenac) : proceedings of a symposium held during the VIIIth European Rheumatology Congress, Helsinki 1975; ISBN: 3456803028; http://www.amazon.com/exec/obidos/ASIN/3456803028/icongroupinterna
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What to Teach Kids About Steroids: For Parents, Teachers, and Other Caregivers (The Parenting for Prevention Information Series) (1998); ISBN: 1562461567; http://www.amazon.com/exec/obidos/ASIN/1562461567/icongroupinterna
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Where the Wildflowers Grow: The True Story of a Steroid-Driven Journey from College Football. by Wilt Browning; ISBN: 1878086332; http://www.amazon.com/exec/obidos/ASIN/1878086332/icongroupinterna
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Winning Without Steroids by Gayle Olinekova, Gayle Olinekiva; ISBN: 0879834803; http://www.amazon.com/exec/obidos/ASIN/0879834803/icongroupinterna
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Workshop on Biotechnology of Antibiotics, Alkaloids and Steroids of Medicinal Importance by R. Vlahov (1991); ISBN: 0895736535; http://www.amazon.com/exec/obidos/ASIN/0895736535/icongroupinterna
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The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “steroids” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Bibliography of the analysis of steroids by gas chromatography. Author: Beckman Instruments, inc. Scientific and Process Instruments Division.; Year: 1965; [Fullerton, Calif., 1965?]
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Chemical and biological synthesis of reproductive steroids.; Year: 1958; Maebashi, Japan, Institute of Endocrinology, Gunma Univ., 1965
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Chemistry of the steroids. Author: Shoppee, Charles William,; Year: 1965; Washington, Butterworth, 1964
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Developments in steroid histochemistry [by] A. H. Baillie and M. M. Ferguson and D. McK. Hart. Author: Baillie, A. H.; Year: 1965; London, New York, Academic Press, 1966
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Gas chromatography of steroids in biological fluids; proceedings. Ed. by Mortimer B. Lipsett. Author: Lipsett, Mortimer B.; Year: 1966; New York, Plenum Press, 1965
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Guide to steroid therapy. Author: Thomas, Picton.; Year: 1965; Philadelphia, Toronto, Lippincott [1968]
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Hormonal steroids; biochemistry, pharmacology, and therapeutics; proceedings of the first International Congress on Hormonal Steroids. Ed. by L. Martini and A. Pecile. Author: Martini, Luciano.; Year: 1964; New York, Academic Press, 1964-
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Introduction to steroid chemistry. Author: Hanson, J. R.; Year: 1965; Oxford, New York, Pergamon Press [1968]
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Long-term ACTH and corticosteroid therapy in bronchial asthma; a clinical evaluation. Author: Arnoldsson, Hans.; Year: 1962; Copenhagen, Munksgaard, 1958
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Metabolism of steroid hormones, by Ralph I. Dorfman [and] Frank Ungar. Author: Dorfman, Ralph I. (Ralph Isadore),; Year: 1965; New York, Academic Press, 1965
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Microbial transformation of steroids and alkaloids, by Hiroshi Iizuka [and] Atsushi Naito. Author: Iizuka, Hiroshi.; Year: 1964; Tokyo, Univ. of Tokyo Press; State College, Pa., University Park Press [c1967]
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Microbial transformations of steroids [by] A. Capek [et al. Translated by Odon Macek et al.]. Author: Capek, A.; Year: 1964; The Hague, Junk, 1966
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Microbial transformations of steroids; a handbook [by] William Charney and Hershel L. Herzog. Author: Charney, William.; Year: 1964; New York, London, Academic Press [c1967]
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Penicillins and cephalosporins. Effects of hormonal steroids on cellular processes; based on symposia held at the April 1967 meeting of the American Pharmaceutical Association Academy of Pharmaceutical Sciences, Las Vagas, Nevada. Edited by D. Perlman. Author: Academy of Pharmaceutical Sciences.; Year: 1966; New York, Interscience Publishers [c1968]
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Principles of steroid analysis. Author: Dale, Sidney L.; Year: 1966; Philadelphia, Lea; Febiger [c1967]
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Regulation of corticosteroidogenesis; a kinetic study of the inhibition of steroidogenesis in adrenal cell-free preparations by c.amp and related compounds. Author: Berger, George Michael B.; Year: 1968; [Minneapolis] 1969
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Steroid analysis by gas liquid chromatography, by A. Anne Patti and Arthur A. Stein. Author: Patti, A. Anne.; Year: 1964; Springfield, Ill., Thomas [c1964]
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Steroid chromatography. Author: Neher, Robert.; Year: 1961; Amsterdam, Elsevier, 1964
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Steroid conjugates: a bibliography, comp. by Seymour Bernstein [et al. Author: Bernstein, Seymour.; Year: 2003; Washington] Chemical Abstracts Service, American Chemical Society [c1966]
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Steroid determinations; applied and theoretical considerations, ed. by Paige K. Besch and Roger D. Barry. Author: Besch, Paige K. (Paige Keith),; Year: 1963; [Park Ridge, Ill., American Medical Technologists, c1964]
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Steroid hormone analysis. Author: Carstensen, Hans.; Year: 1966; New York, Dekker, 1967-
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Steroid-Spektrenatlas. Atlas of steroid spectra [von] Walter Neudert [und] Horst Röpke. Englische Ubersetgung v John B. Leane. Author: Neudert, Walter.; Year: 1963; Berlin, Springer, 1965
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The biosynthesis of steroids, terpenes, and acetogenins [by] John H. Richards and James B. Hendrickson. Author: Richards, John Hall,; Year: 1964; New York, Benjamin, 1964
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The Chemistry and biochemistry of steroids [by] Leland J. Chinn [et al.]. Author: Chinn, Leland J.; Year: 1967; Los Altos, Calif., Geron-X, 1969
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The gas liquid chromatography of steroids; proceedings of a symposium held at the University of Glasgow on 4 to 6 April 1966. Ed. by J. K. Grant. Author: Society for Endocrinology (Gt. Brit.); Year: 1968; Cambridge [Eng.] University Press, 1967
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The synthesis of sterols and the effects of steroids in Chlorella. Author: Patterson, Glenn W.,; Year: 1964; College Park, Md., 1963
Chapters on Steroids In order to find chapters that specifically relate to steroids, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and steroids using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “steroids” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on steroids:
Books 469
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Topically Active Corticosteroids for Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 73-76. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of topically active corticosteroids for treating colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). UC universally involves the rectum, but the proximal extent (how far it goes) of the disease is variable. When inflammation is limited to the rectum (proctitis) or to the sigmoid colon (proctosigmoiditis), the symptoms of urgency, tenesmus (straining to defecate), and bleeding cause substantial impact on daily activities, but systemic complications are lower when compared to panulcerative colitis. Topical administration of corticosteroids has been a mainstay of primary therapy for distal ulcerative colitis over several decades and also is a useful adjunct to oral therapy for more extensive disease. However, conventional corticosteroids may be associated with a spectrum of undesirable side effects and thus newer steroid formulations have emerged that provide advantages over conventional steroid preparations. The composite clinical experience indicates that topical 5-ASA (aminosalicylates) preparations will usually provide greater efficacy for distal ulcerative colitis. However, in the patient who is refractory to 5-ASA therapy or shows true 5-ASA sensitivity, topical hydrocortisone foam or budesonide may prove to be useful. Further refinements of the colonic release systems for oral budesonide enterocapsules (taken orally, but the drug is not released from the capsule until it reaches the intestine or colon) may be of benefit to patients with more extensive ulcerative colitis. 11 references.
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Appropriate Use of Corticosteroids in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 363-366. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of corticosteroids in managing inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as IBD. Glucocorticoids are a mainstay for the treatment of severe IBD. The efficacy of corticosteroids to induce remission in both CD and Ulcerative Colitis (UC) has been well established in large randomized controlled trials. At times, a focus on adverse events has diminished the recognition of the usefulness of corticosteroids. The authors suggest approaches for the appropriate use of corticosteroids, including corticosteroid-sparing strategies, in patients with IBD. Corticosteroids used in the treatment of IBD are prednisone, prednisolone, methylprednisolone, and budesonide. Prednisone and prednisolone have comparable glucocorticoid potency, whereas methylprednisolone is slightly more potent. In IBD, their use should be restricted to severe, active disease, with the aim of inducing
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remission. Simple dosing considerations can decrease the possibility of serious side effects. For example, steroids should be given as a single morning dose to coincide with the natural circadian rhythm of endogenous (naturally occurring in the body) corticosteroids. Corticosteroid sparing strategies incorporate the use of nutrition, budesonide, aminosalicylates, antibiotics, azathioprine and 6 mercaptopurine (immunomodulators), methotrexate, cyclosporine, and anti-tumor necrosis factor alpha. 13 references. •
Steroids or Nutrition? Source: Jewell, D.P. Warren, B.F. Mortensen, N.J., eds. Challenges in Inflammatory Bowel Disease. Malden, MA: Blackwell Science, Inc. 2001. p.111-120. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $145.95. ISBN: 0632051698. Summary: In this chapter, from a book that offers an approach to the subject of inflammatory bowel disease (IBD) that highlights current areas of controversy, the author considers the role of steroids (glucocorticoids) and medical nutrition therapy for IBD. The author first examines the use of glucocorticoids. The authors stresses that the disadvantages associated with steroids are particularly relevant in diseases such as ulcerative colitis (UC) and Crohn's disease (CD) with a clinical course characterized by frequent relapses that may need repeated courses of treatment. There are esthetic sideeffects, metabolic consequences including growth failure in children and adolescents, and the development of osteopenia (bone disease) associated with the use of steroids in IBD. The author then introduces the rationale for the use of nutritional management as primary therapy in IBD and reviews numerous studies that consider this treatment approach. The author concludes that enteral nutrition is indicated as first choice treatment for CD in children and adolescents, because in addition to the observed clinical, biological and endoscopic antiinflammatory effect, it will prevent or minimize growth failure, sexual development delay, and osteopenia. For similar reasons enteral nutrition can be used as the first treatment in other patient populations with CD, including the elderly, patients with undiagnosed abdominal abscess, and patients with steroid dependence. 2 figures. 2 tables. 103 references.
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Topical Steroids Source: in Peppercorn, M.A., ed. Therapy of Inflammatory Bowel Disease: New Medical and Surgical Approaches. New York, NY: Marcel Dekker, Inc. 1990. p. 35-41. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701-5185. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail:
[email protected]. PRICE: $190.00. ISBN: 0824781694. Summary: Corticosteroids and/or sulfasalazine continue to be the cornerstones of antiinflammatory therapy for inflammatory bowel disease (IBD). Intermediate and longterm toxicity and side effects for both of these compounds have prompted the search for less toxic agents. This chapter, from a book about new medical and surgical approaches to the treatment of IBD, discusses the use of rectally instilled therapeutic agents. The rationale for the use of topical steroids is, in part, based upon the natural history of leftsided ulcerative colitis. The relatively benign nature of left-sided disease allows time for judgment in the selection of appropriate agents to suppress inflammatory activity and ameliorate symptoms. The author discusses two major classes of compounds under
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study: poorly absorbed steroids, including prenisolone-21-metasulphobenzoate, and absorbable steroids with no systemic side effects, such as beclomethasone dipropionate and tixocortol pivalate. These agents possess effective topical anti-inflammatory activity without producing the significant side effects or long-term toxicity commonly associated with absorbable systemic corticosteroids. 16 references. •
Steroid Unresponsiveness in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 133-137. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Although systemic glucocorticoid treatment is associated with a large number and sometimes severe side effects, this is still the first and most useful therapeutic tool in treating patients with both acute ulcerative colitis (UC) and Crohn's disease (CD). In these clinical situations, glucocorticoids are both rapidly acting, within 48 hours, and effective, with a response rate of about 80 percent. Unresponsiveness to steroid treatment leads to the need for therapeutic decisions including surgical resection or the use of immunosuppressive drugs. This chapter on steroid unresponsiveness is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with CD and UC, together known as inflammatory bowel disease (IBD). When a patient presents with steroid resistance, it is important to rule out false causes of refractoriness, such as bile-salt malabsorption, bacterial overgrowth, and coexistent irritable bowel syndrome. It also is important to detect the existence of viral or bacterial gastrointestinal infections that may enhance the synthesis of inflammatory mediators perpetuating the disease process. The molecular basis of genuine steroid resistance is unclear but an understanding will allow earlier diagnosis and treatment. Therapeutic alternatives to steroids should be individualized; the author outlines a personal schematic approach in a patient care algorithm. 2 figures. 12 references.
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Topically Active Steroid Preparations Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 367-371. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on topically active steroid preparations is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Glucocorticosteroids (GCS) remain the mainstay of primary medical treatment for induction of remission in moderate and severe attacks of CD. The anti-inflammatory effects of GCS in active CD are unsurpassed by any other type of drug. However, drawbacks with conventional GCS include problems with a wide array of side effects and the risk for steroid dependency in a substantial proportion of patients who initially respond favorably to the treatment. Elimination of, or at least a substantial reduction of, unwanted short-and long-term
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systemic side effects would make GCS an even more important anti-inflammatory modality for the treatment of CD. Efforts in developing superior steroids for IBD aim at obtaining increased and selective topical action, with no, or only limited, systemic impact. The author focuses on oral budesonide preparations, including the ileal release (the drug is in a capsule that does not disintegrate until it is in the intestinal location where it is designed to be of topical use) formulation of this drug. The optimal dose of oral budesonide for induction of remission in active CD is 9 milligrams per day. Budesonide appears to be particularly versatile in combination with other drugs, including metronidazole, ciprofloxacin, mesalamine, and sulfasalazine, for treatment of IBD. 1 figure. 11 references.
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CHAPTER 8. MULTIMEDIA ON STEROIDS Overview In this chapter, we show you how to keep current on multimedia sources of information on steroids. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on steroids is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “steroids” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “steroids” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on steroids: •
AIDS Risk: It's Your Choice Contact: American Institute for Teen AIDS Prevention, Teen Choice, PO Box 395, Oberlin, OH, 44074-0395, (440) 774-3353. Summary: This videorecording shows Acquired immunodeficiency syndrome (AIDS) educator Duane Crumb giving a speech at an assembly at Polytechnic High School in Fort Worth, TX. Crumb addresses their fears about Human immunodeficiency virus (HIV) infection, and stresses the need for compassion toward Persons with AIDS (PWA's). He gives the students a summary of AIDS information, starting with what the letters in AIDS stand for, and HIV as the causative agent of the disease. He presents statistics on infection and uses the iceberg analogy to show the numbers of HIV-infected persons. Crumb outlines the routes of HIV transmission, emphasizing the risks through pregnancy, IV-needle sharing, and sexual intercourse. He tells the students that it's not the drugs that transmit HIV, it's the needles, and that the danger is just as great from shooting steroids, piercing ears, or being tattooed. He mentions sterilizing needles with bleach. The students hear that abstinence from sex is the best method of HIV prevention,
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along with statistics on adolescent pregnancy and Sexually transmitted diseases (STD's). He explains condom use, emphasizing that the failure rate is about 10 percent. Crumb tells the students that HIV is not transmitted through casual contact, presenting details on families who live together but do not contract AIDS; therefore, sitting next to an infected person in class poses no danger. He urges them to be friends with PWA's. The speech concludes with a question-and-answer session, where students ask about opportunistic infections; the risks from kissing, sharing drinking glasses, mosquitoes, and swimming pools; symptoms; and treatments. •
It's Your Choice Contact: American Institute for Teen AIDS Prevention, Teen Choice, PO Box 395, Oberlin, OH, 44074-0395, (440) 774-3353. Summary: This videorecording shows Acquired immunodeficiency syndrome (AIDS) educator Duane Crumb giving a speech at an assembly at Polytechnic High School in Fort Worth, TX. Crumb addresses their fears about Human immunodeficiency virus (HIV) infection, and stresses the need for compassion toward Persons with AIDS (PWA's). He gives the students a summary of AIDS information, starting with what the letters in AIDS stand for, and HIV as the causative agent of the disease. He presents statistics on infection and uses the iceberg analogy to show the numbers of HIV-infected persons. Crumb outlines the routes of HIV transmission, emphasizing the risks through pregnancy, IV-needle sharing, and sexual intercourse. He tells the students that it's not the drugs that transmit HIV, it's the needles, and that the danger is just as great from shooting steroids, piercing ears, or being tattooed. He mentions sterilizing needles with bleach. The students hear that abstinence from sex is the best method of HIV prevention, along with statistics on adolescent pregnancy and Sexually transmitted diseases (STD's). He explains condom use, emphasizing that the failure rate is about 10 percent. Crumb tells the students that HIV is not transmitted through casual contact, presenting details on families who live together but do not contract AIDS; therefore, sitting next to an infected person in class poses no danger. He urges them to be friends with PWA's. The speech concludes with a question-and-answer session, where students ask about opportunistic infections; the risks from kissing, sharing drinking glasses, mosquitoes, and swimming pools; symptoms; and treatments.
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Pre and Post Operative Care Source: Toronto, Ontario, Canada: Medical Audio Visual Communications, Inc. 1994. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $350.00 (Canadian); contact producer for current price in American dollars. Summary: This videocassette on pre-and postoperative care is one from a series of three programs that provides information for nurses and other medical personnel who are caring for a transplant patient. The program discusses and demonstrates the preoperative preparation of the organ recipient, pathophysiology, nursing interventions, immunosuppressive medications, steroids and other medications, and side effects of the medications. The video reviews possible complications after surgery and gives the viewer information on signs and symptoms of rejection. Along with the necessary clinical information, family members and patients discuss their transplant experiences. (AA-M).
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Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “steroids” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on steroids: •
The Three A's of AIDS: Anxiety, Anger & Alienation in Young Athletes; 15th National Lesbian & Gay Health Conference & 11th Annual AIDS/HIV Forum; Houston, TX, July 20-25, 1993 Contact: Encore Cassettes, PO Box 231340, San Diego, CA, 92194, (619) 596-8402. Summary: This sound recording is of a session dealing with young athletes and their attitudes toward AIDS. The speaker, a counselor in Southern California, discusses many issues typically associated with adolescents and AIDS, such as the immortality myth. Differences arise, however, because athletes face a "double death" -- the death of their athletic career as well as their own death. They also tend to believe that because they are practicing and exercising with no problems, they could not possibly be HIV-positive and have no need to be tested in spite of risky sexual behavior or sharing needles for steroids. Coaches may complicate the problem by encouraging promiscuous behavior as part of the athletic mystique and promoting homophobic attitudes towards young gay athletes.
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AIDS in Children and Adults Contact: InfoMedix, 12800 Garden Grove Blvd, Ste F, Garden Grove, CA, 92643, (714) 530-3454. Summary: This sound recording of the American Academy of Allergy and Immunology's 45th Annual Meeting, held February 24 - March 1, 1989, in San Antonio, TX, on children and Acquired immunodeficiency syndrome (AIDS), presents a discussion of the implementation of immunotherapy for the treatment of AIDS and Human immunodeficiency virus (HIV) infection, including asymptomatic cases. It examines the therapeutic procedure and its efficacy on the immune system at the molecular level. It also discusses the late-phase responses in asthma; damage to the immune system; and the use of inhaled steroids for asthma, as well as for HIVinfected persons and children with LIP. Allergy immunization with HIV infection with different pharmacological therapy is also discussed. Changes in the Centers for Disease Control and Prevention (CDC) universal precautions are examined regarding the use of gloves for protection from HIV exposure through accidental blood spills. A placebo-controlled study which utilizes azidothymidine (AZT) for HIV-needlestick injuries is mentioned, together with a number to join the study.
Bibliography: Multimedia on Steroids The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in steroids (or synonyms). Then, in
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the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on steroids: •
Effect of contraceptive steroids on mammary tumour development in beagles [slide] Source: M.F. El Etreby; Year: 1980; Format: Slide; Oxford; New York: Pergamon, 1980
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Medical aspects of sports medicine--drugs, steroids & substance abuse in sports medicine [videorecording]: August 10-15, 1993 Source: CME Conference Video, Inc. sponsored by American College of Sports Medicine; Year: 1993; Format: Videorecording; Mt. Laurel, NJ: CME Conference Video, c1993
•
Rational use of steroids [videorecording] Source: Continuing Education in Health Sciences Univ. of California, San Francisco Medical Center with the assistance of the medical institutions of Northern California; Year: 1967; Format: Videorecording; San Francisco: Univ. of Calif., Education TV Div., [1967]
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Rational use of steroids in dermatology [videorecording] Source: presented by Department of Pediatrics, Emory Univ., School of Medicine; Year: 1981; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1981
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Steroid biosynthesis [slide] Source: by Robert L. Folk; Year: 1974; Format: Slide; Oak Brook, Ill.: Educational Products; [Walpole, Mass.: for sale by Edupac], c1974
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Steroid metabolism [slide] Source: Robert L. Folk; [produced by] Independent Study Program, College of Medicine, Ohio State University; Year: 1974; Format: Slide; Oak Lawn, Ill.: Educational Products; [Walpole, Mass.: for sale by EDUPAC], c1974
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Steroids: truths and untruths [sound recording]; glucocorticosteroids Source: Coummunications in Learning; Year: 1977; Format: Sound recording; Buffalo: Communications in Learning, 1977
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Steroids [videorecording] Source: CE, Cambridge Educational; Year: 1999; Format: Videorecording; Charleston, WV: Cambridge Educational, c1999
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Steroids [videorecording]: the hormonal time bomb Source: Visions Video Productions; Year: 1991; Format: Videorecording; [Evanston, IL]: Visions Video Production, c1991
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Steroids and immunosuppressive drugs in renal disease [motion picture] Source: Video Digest, inc; Year: 1972; Format: Motion picture; Cincinnati, Ohio: Video Digest, c1972
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CHAPTER 9. PERIODICALS AND NEWS ON STEROIDS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover steroids.
News Services and Press Releases One of the simplest ways of tracking press releases on steroids is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “steroids” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to steroids. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “steroids” (or synonyms). The following was recently listed in this archive for steroids: •
Rehab added to steroids benefits MS patients after relapse Source: Reuters Medical News Date: October 07, 2003 http://www.reutershealth.com/archive/2003/10/07/professional/links/20031007clin0 02.html
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•
Inhaled steroid use may raise cataract risk Source: Reuters Medical News Date: September 18, 2003
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Steroids for bowel disease up fracture risk Source: Reuters Health eLine Date: September 10, 2003
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Asthma, inhaled steroids do not seem to lead to varicella vaccination failure Source: Reuters Medical News Date: August 13, 2003
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Systemic corticosteroids quell pediatric asthma exacerbations Source: Reuters Medical News Date: August 11, 2003
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Corticosteroid response trials diagnostically useless for COPD patients Source: Reuters Medical News Date: August 06, 2003
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Steroid iontophoresis, topical nitric oxide relieve pain of epicondylitis Source: Reuters Medical News Date: July 30, 2003
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Montelukast has additive and steroid-sparing effects in asthmatic children Source: Reuters Medical News Date: July 25, 2003
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Steroids may reduce need for ER asthma treatment Source: Reuters Health eLine Date: July 24, 2003
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Outpatient systemic steroids may improve acute asthma care in inner-city adults Source: Reuters Medical News Date: July 24, 2003
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Inhaled steroids ameliorate nocturnal worsening of asthma Source: Reuters Medical News Date: July 10, 2003
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Inhaled steroids do not slow COPD-related lung function decline Source: Reuters Medical News Date: June 17, 2003
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Mifepristone's neuroprotective effect independent of steroid receptors Source: Reuters Medical News Date: June 06, 2003
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Trial shows safety of steroid stepdown in more severe asthma Source: Reuters Medical News Date: May 22, 2003
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Physical therapy as good as corticosteroid injection for acute shoulder pain Source: Reuters Medical News Date: May 16, 2003
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BMD declines after alendronate therapy is stopped in patients on steroids Source: Reuters Medical News Date: May 09, 2003
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Steroid pulse therapy improves Parkinson's-related malignant syndrome Source: Reuters Medical News Date: May 08, 2003
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New inhaled steroid safe and effective in patients with bronchial asthma Source: Reuters Medical News Date: April 22, 2003
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Steroid withdrawal regimen appears successful after first renal transplant Source: Reuters Medical News Date: April 03, 2003
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No benefit seen with montelukast added to inhaled steroids in mild asthma Source: Reuters Medical News Date: March 28, 2003
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Inhaled steroids may help mild asthma: study Source: Reuters Health eLine Date: March 28, 2003
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Steroids not required for Graves' patients with stable eye disease Source: Reuters Medical News Date: March 26, 2003
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Lawmakers probe steroid, weight-loss products Source: Reuters Health eLine Date: March 26, 2003
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Intrapleural steroids not effective for malignant effusions Source: Reuters Medical News Date: March 25, 2003
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Anabolic steroid use may lead to opioid abuse Source: Reuters Medical News Date: March 25, 2003
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Long-term steroids increase heart risk: study Source: Reuters Health eLine Date: March 24, 2003
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Long-term steroid use increases heart disease risk Source: Reuters Medical News Date: March 24, 2003
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For some, anabolic steroids may lead to hard drugs Source: Reuters Health eLine Date: March 24, 2003
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Inhaled steroids more effective than anti-leukotrienes in controlling asthma Source: Reuters Medical News Date: March 20, 2003
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Long-term intraarticular steroid injection safe for knee osteoarthritis Source: Reuters Medical News Date: February 28, 2003
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Inhaled steroid use not associated with bone density changes in women Source: Reuters Medical News Date: February 28, 2003
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Short courses of oral steroids safe in pediatric asthma Source: Reuters Medical News Date: February 24, 2003
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Calcium, bisphosphonates cost effective in preventing fractures in steroid-treated women Source: Reuters Medical News Date: February 10, 2003
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Short-course steroids for asthma may not harm bone Source: Reuters Health eLine Date: February 07, 2003
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Higher-dose steroids offer greater survival benefit in COPD Source: Reuters Medical News Date: February 04, 2003
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Inhaled steroids may not reduce women's bone mass Source: Reuters Health eLine Date: January 28, 2003
Periodicals and News 481
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Additional Hib immunization may benefit preterm steroid-treated infants Source: Reuters Medical News Date: January 07, 2003 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “steroids” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “steroids” (or synonyms). If you know the name of a company that is relevant to steroids, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “steroids” (or synonyms).
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “steroids” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on steroids: •
Benefits of Low-dose Corticosteroids in Rheumatoid Arthritis Source: Bulletin on the Rheumatic Diseases. 46(4):4-7; June 1997. Contact: Arthritis Foundation. 1330 West Peachtree Street; Atlanta, GA 30309. (404) 8727100. Fax (404) 872-9559. Summary: This newsletter article for health professionals considers the benefits of lowdose corticosteroids in treating rheumatoid arthritis (RA). The mechanism of action of corticosteroids is explained, and studies on the disease-modifying effects of corticosteroids are reviewed. Careful analysis of some study data suggests beneficial effects of corticosteroids in RA. However, the potential toxicity of corticosteroids has been well-documented. Common side effects include interfering with glucose tolerance, increasing lipoproteins and serum lipids, elevating blood pressure, increasing the likelihood of osteoporosis, and causing muscle weakness and myopathy. In addition, the use of alternate-day and pulse steroids is discussed. The article concludes that corticosteroids are an important therapeutic option for individuals with RA. 18 references.
Academic Periodicals covering Steroids Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to steroids. In addition to these sources, you can search for articles covering steroids that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for steroids. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with steroids. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to steroids: Aminoglutethimide •
Systemic - U.S. Brands: Cytadren http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202026.html
Anabolic Steroids •
Systemic - U.S. Brands: Anadrol-50; Deca-Durabolin; Durabolin; Durabolin-50; Hybolin Decanoate; Hybolin-Improved; Kabolin; Oxandrin; Winstrol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202035.html
Anesthetics •
Rectal - U.S. Brands: Americaine Hemorrhoidal; Fleet Relief; Nupercainal; Pontocaine Cream+; Pontocaine Ointment; ProctoFoam/non-steroid; Tronolane; Tronothane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202041.html
Anti-Inflammatory Drugs, Nonsteroidal •
Ophthalmic - U.S. Brands: Ocufen; Profenal; Voltaren Ophthalmic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202647.html
•
Systemic - U.S. Brands: Actron; Advil; Advil Caplets; Advil, Children's; Aleve; Anaprox; Anaprox DS; Ansaid; Bayer Select Ibuprofen Pain Relief Formula Caplets; Cataflam; Clinoril; Cotylbutazone; Cramp End; Daypro; Dolgesic; Dolobid; EC-Naprosyn; Excedrin IB; Excedrin IB Caple http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202743.html
Clotrimazole and Betamethasone •
Topical - U.S. Brands: Lotrisone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202156.html
Corticosteroids •
Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html
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Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html
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Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html
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Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P. HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html
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Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html
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•
Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html
Corticosteroids Glucocorticoid Effects •
Systemic - U.S. Brands: Acetocot; A-hydroCort; Amcort; A-MethaPred; Aristocort; Aristocort Forte; Aristopak; Aristospan; Articulose-50; Articulose-L.A. Celestone; Celestone Phosphate; Celestone Soluspan; Cinalone 40; Cinonide 40; Clinacort; Clinalog; Cordrol; Cortastat; Corta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202018.html
Corticosteroids Low Potency •
Topical - U.S. Brands: 9-1-1; Aclovate; Acticort 100; Aeroseb-Dex; Aeroseb-HC; Ala-Cort; Ala-Scalp HP; Allercort; Alphaderm; Bactine; Beta-HC; CaldeCORT Anti-Itch; CaldeCORT Light; Carmol-HC; Cetacort; Cloderm; Cortaid; CortDome; Cortef Feminine Itch; Corticaine; Cortifair; http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202907.html
Corticosteroids Medium to Very High Potency •
Topical - U.S. Brands: Alphatrex; Aristocort 20; Aristocort A 20; Betatrex; BetaVal; Bio-Syn; Cordran; Cordran SP; Cormax; Cutivate; Cyclocort; Delta-Tritex 20; Dermabet; Dermatop; Diprolene; Diprolene AF; Diprosone; Elocon; Florone; Florone E; Fluocet; Fluocin; Fluonid; Flu http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202016.html
Cromolyn •
Inhalation - U.S. Brands: Intal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202166.html
Docetaxel •
Systemic - U.S. Brands: Taxotere http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202920.html
Dornase Alfa •
Inhalation - U.S. Brands: Pulmozyme http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202710.html
Fludrocortisone •
Systemic - U.S. Brands: Florinef http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202244.html
Fluticasone •
Inhalation-Local - U.S. Brands: Flovent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203649.html
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Nasal - U.S. Brands: Flonase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203588.html
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Hydrocodone and Ibuprofen •
Systemic - U.S. Brands: Vicoprofen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203600.html
Ivermectin •
Systemic - U.S. Brands: Stromectol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202311.html
Ketorolac •
Ophthalmic - U.S. Brands: Acular http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202714.html
•
Systemic - U.S. Brands: Toradol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202318.html
Loteprednol •
Ophthalmic - U.S. Brands: Alrex; Lotemax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203541.html
Meloxicam •
Systemic - U.S. Brands: Mobic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500131.html
Mitotane •
Systemic - U.S. Brands: Lysodren http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202377.html
Mometasone •
Nasal - U.S. Brands: Nasonex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203589.html
Nedocromil •
Inhalation - U.S. Brands: Tilade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202681.html
Neomycin, Polymyxin B, and Hydrocortisone •
Otic - U.S. Brands: Cort-Biotic; Cortisporin; Cortomycin; Drotic; Ear-Eze; LazerSporin-C; Octicair; Octigen; Otic-Care; Otimar; Otisan; Otocidin; Otocort; Pediotic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202403.html
Nystatin and Triamcinolone •
Topical - U.S. Brands: Dermacomb; Mykacet; Mytrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202420.html
Rimexolone •
Ophthalmic - U.S. Brands: Vexol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203590.html
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Risedronate •
Systemic - U.S. Brands: Actonel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203554.html
Rofecoxib •
Systemic - U.S. Brands: Vioxx http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203782.html
Salicylates •
Systemic - U.S. Brands: Acuprin 81; Amigesic; Anacin Caplets; Anacin Maximum Strength; Anacin Tablets; Anaflex 750; Arthritis Pain Ascriptin; Arthritis Pain Formula; Arthritis Strength Bufferin; Arthropan; Aspergum; Aspirin Regimen Bayer Adult Low Dose; Aspirin Regimen Bayer R http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202515.html
Sirolimus •
Systemic - U.S. Brands: Rapamune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500028.html
Thiabendazole •
Systemic - U.S. Brands: Mintezol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202558.html
Tobramycin and Dexamethasone •
Ophthalmic - U.S. Brands: Tobradex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203776.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.
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Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to steroids by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “steroids” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for steroids: •
Troleandomycin http://www.rarediseases.org/nord/search/nodd_full?code=204
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Dehydroepiandrosterone http://www.rarediseases.org/nord/search/nodd_full?code=458
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “steroids” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “steroids” (or synonyms) into the “For these words:” box. The following is a sample result: •
Anabolic Steroids Contact: AIDS Project Los Angeles, 3550 Wilshire Blvd Ste 300, Los Angeles, CA, 900102404, (213) 201-1600, http://www.apla.org. Summary: This fact sheet compiles case studies on the effects of anabolic steroids to combat weight loss in HIV-positive persons. An HIV-positive physician details his personal plan of success which combines diet, supplements, moderate exercise, and steroids he obtains from Germany. He discusses non-steroid supplements which he considers of no benefit. Researchers may be reluctant to study steroids due to the lack of profitability and the negative stigma attached to misuse. The benefits of steroid use are described, including increase in muscle weight, in energy, in immune system function, and in sense of well-being. Long-term side effects like coronary artery disease and nonviral hepatitis appear less important since malnutrition is a common cause of death in AIDS patients. The alternative therapies discussed warrant further research, particularly due to their apparent success, their low cost, and their potential cost savings by prevention of secondary infections.
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Anabolic Steroids: A Threat to Body and Mind Contact: US Department of Health and Human Services, Public Health Service, Substance Abuse and Mental Health Service Administration, Rockville, MD, 20850. Summary: This report studies the growing nonmedical use of anabolic/androgenic steroids among adolescents and young adults. This usage is often related to sports, as athletes attempt to improve their performance by bulking up physically with the aid of the drugs. However, people also take steroids solely to improve their appearance. Based on findings from recent studies, this report looks at the side effects and other dangers connected with abusing steroids. It points out that if shared needles are used to inject the drugs, there is a danger of HIV transmission.
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The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “steroids” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 477285 1636 318 217 5 479461
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “steroids” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Steroids In the following section, we will discuss databases and references which relate to the Genome Project and steroids. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “steroids” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for steroids:
21
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23
Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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17-@beta-hydroxysteroid Dehydrogenase Vii Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606756
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17-@beta-hydroxysteroid Dehydrogenase Viii Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601417
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3-@alpha-hydroxysteroid Epimerase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606623
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3-@beta-hydroxy-delta-5-c27-steroid Oxidoreductase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607764
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Adrenal Hyperplasia, Congenital, due to Defects in Several Steroid-biosynthetic Enzymes Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?201750
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Steroid 5-alpha-reductase 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607306
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Steroidogenic Acute Regulatory Protein Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600617 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “steroids” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “steroids” (or synonyms) into the search box, and
24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on steroids can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to steroids. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to steroids. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “steroids”:
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Other guides About Your Medicines http://www.nlm.nih.gov/medlineplus/aboutyourmedicines.html Anabolic Steroids http://www.nlm.nih.gov/medlineplus/anabolicsteroids.html Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.html
Within the health topic page dedicated to steroids, the following was listed: •
General/Overviews Anabolic Steroids http://www.acsm.org/pdf/STEROIDS.pdf Hormone Abuse Source: Hormone Foundation http://www.hormone.org/learn/abuse_1.html Steroids Source: Office of National Drug Control Policy http://www.whitehousedrugpolicy.gov/drugfact/steroids/index.html
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Treatment Principles of Drug Addiction Treatment: A Research-Based Guide Source: National Institute on Drug Abuse http://www.nida.nih.gov/PODAT/PODATindex.html
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Specific Conditions/Aspects Banned Substances Enhance Athletic Performance, but at a Price Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SM00038 Mind Over Matter - The Brain's Response to Steroids Source: National Institute on Drug Abuse http://www.nida.nih.gov/MOM/ST/MOMST1.html Natural Steroids: Are They Safer? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00226 Physical and Psychological Risks of Anabolic Steroid Use Source: National Clearinghouse for Alcohol and Drug Information http://ncadi.samhsa.gov/nongovpubs/steffects/ Steroids -- Dangerous Side Effects
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Source: American Academy of Pediatrics http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZT6QV5M7C &sub_cat=405 •
Children Steroids Quest Source: National Institute on Drug Abuse http://www.sarasquest.org/Quest/Steroids/Stertest1.html
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From the National Institutes of Health Anabolic Steroid Abuse Source: National Institute on Drug Abuse http://www.nida.nih.gov/ResearchReports/Steroids/AnabolicSteroids.html Anabolic Steroids: Community Drug Alert Bulletin Source: National Institute on Drug Abuse http://www.nida.nih.gov/SteroidAlert/SteroidAlert.html
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Law and Policy Steroids Source: Drug Enforcement Administration http://www.usdoj.gov/dea/concern/steroids.html
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Organizations Drug Enforcement Administration http://www.usdoj.gov/dea/ National Clearinghouse for Alcohol and Drug Information Source: Dept. of Health and Human Services, Substance Abuse and Mental Health Services Administration http://www.health.org/ National Institute on Drug Abuse http://www.nida.nih.gov/NIDAHome.html Office of National Drug Control Policy http://www.whitehousedrugpolicy.gov/
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Research Study Provides Additional Evidence That High Steroid Doses Elicit Psychiatric Symptoms in Some Men Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_Notes/NNVol15N4/Study.html
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Statistics High School and Youth Trends Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/HSYouthtrends.html
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Teenagers Are Steroids Worth the Risk? Source: Nemours Foundation http://kidshealth.org/teen/food_fitness/sports/steroids.html Steroids: Play Safe, Play Fair Source: American Academy of Pediatrics http://www.aap.org/family/steroids.htm Teens and Steroids: Drug Use Rising Despite Dangers Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SA00076
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on steroids. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Drugs, Tattoos, Piercing, Steroids and HIV/AIDS : How to Make Them Safer. In Prison Contact: SIDA Nouveau Brunswick/AIDS New Brunswick, 65 Brunswick St, Fredericton, (506) 459-7518, http://www.aidsnb.com. Summary: This brochure informs inmates about the safe use of needles for injection drugs use, piercings, tattoos, and steroids to help to prevent the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). The brochure warns that sharing needles or other items (e.g., threads, inks, spoons) associated with these activities can transmit HIV/AIDS or hepatitis, and presents instructions concerning the sterilization of needles with bleach. It advises the readers about other liquids that they can use to clean their needle works. The brochure describes how to reduce the readers risks for HIV transmission while using needles for piercings or tattoos. Additional sources of information are provided.
•
Intramuscular Steroids and HIV/AIDS: Lift the Weight off Your Mind. Don't Share Vials and Used Needles Contact: HIV/AIDS Regional Services, PO Box 120, Kingston, (613) 545-3698, http://www1.kingston.net/~hars.
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Summary: This brochure outlines potential negative effects from anabolic steroid use, focusing on the risk of contracting HIV/AIDS through the sharing of needles. It defines HIV/AIDS, including ways in which it can and cannot be transmitted. One section discusses how steroid use can be a risk factor through the practice of flagging, followed by shared needle use, or the sharing of vials. Other arguments against steroid use are also presented, including: increased aggressiveness; disruption of normal growth and permanent infertility in adolescents; increased risk of other infectious diseases, such as hepatitis; and the particular risks for women. A final section describes and urges HIV testing. •
Do You Know. Steroids Contact: Addiction Research Foundation, 33 Russell St, Toronto, (416) 595-6000. Summary: This brochure presents basic information about anabolic steroids, a chemically manufactured version of the male sex hormone, testosterone. It looks at the following issues: possible medical uses for anabolic steroids, topics related to sports, how steroids affect persons, and steroid dangers. It points out those who inject steroids also run the risk of infection from dirty needles, and of hepatitis or Human immunodeficiency virus (HIV) infection if they share needles with others. Also, steroids affect the immune system in a similar way to HIV.
•
Steroids in the Treatment of Lupus Source: Rockville, MD: Lupus Foundation of America. 1999. 6 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. PRICE: Available as part of a package of 21 different lupus related brochures for $3.95 plus shipping and handling. Summary: This pamphlet provides people who have lupus with information on using steroids to treat the symptoms resulting from inflammation in various tissues. People should take the lowest possible effective dose of steroids and should never suddenly stop taking them after more than 4 weeks. Cortisone, which is manufactured by the body's adrenal glands and is also made synthetically, has been found to reduce inflammation. Steroids produced by the outer part of the adrenal gland are called corticosteroids. Prednisone is the synthetic corticosteroid most often used to treat lupus. The pamphlet discusses dosage, mode of administration, and common side effects, such as a change in appearance, psychological effects, and an increase in susceptibility to infections. In addition, side effects of long-term use include avascular necrosis of bone, osteoporosis, cataracts, and muscle weakness. The pamphlet also provides information on the Lupus Foundation of America. 1 table.
•
Steroids Source: Portland, OR: National Psoriasis Foundation. 1998. 12 p. Contact: Available from National Psoriasis Foundation. P.O. Box 9009, Portland, OR 97207-9009. (800) 723-9166 Ext. 12 or (503) 244-7404. Fax (503) 245-0626. E-mail:
[email protected]. Website: www.psoriasis.org. PRICE: $0.35 each plus shipping and handling; bulk orders available. Summary: This pamphlet uses a question and answer format to provide people who have psoriasis with information on treatment with topical steroids, which are an easy to use, effective way of controlling mild to moderate lesions. Steroid medications work by
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making skin cells reproduce at a slower rate and decreasing inflammation. Topical steroids come in strengths ranging from very weak to very strong. The pamphlet presents methods of using topical steroids, such as applying them directly onto lesions to form a thin layer; applying them and covering the area with airtight plastic wrap, a cellophane dressing, an occlusive waterproof dressing, or a nylon suit; and using a pulse-dosing application regimen. Other topics discussed include using topical steroids to treat scalp psoriasis, treating children, and using these medications during pregnancy and while breastfeeding. In addition, the pamphlet identifies side effects, offers practical tips on using topical steroids, discusses the internal use of steroids, and concludes with information on the National Psoriasis Foundation. 1 appendix and 1 table. •
If You Use Steroids, These [Barbells] Aren't the Only Thing Stacked Against You Source: Chicago, IL: American Academy of Orthopaedic Surgeons. 1993. 4 p. Contact: Available from American Academy of Orthopaedic Surgeons (AAOS). P.O. Box 75838, Chicago, IL 60675-5838. (800) 626-6726. Fax (for credit card or institutional purchase orders) (800) 823-8025. Web site: www.aaos.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet warns the general public about the dangers of using anabolic steroids to improve athletic performance or appearance. Anabolic steroids may cause acne or hair loss, permanently stunt growth, make tendons tear or rupture, and render the user uncontrollably aggressive and combative. Men using anabolic steroids may experience testicular shrinkage, and women using them can develop facial hair, a deeper voice, and irregular menstrual periods.
•
Facts About Dietary Supplements for the Warfighter: Herbs and Botanicals, Amino Acids, Steroids, Vitamins and Minerals Source: Abderdeen Proving Ground, MD: U.S. Army Center for Health Promotion and Preventive Medicine. 2003. [2 p.]. Contact: Available from U.S. Army Center for Health Promotion and Preventive Medicine. 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5403. (800) 2229698. PRICE: Free. Summary: This brochure, produced for the U.S. Army Center for Health Promotion and Prevention Medicine, provides information about dietary supplements, specifically herbs and botanicals, amino acids, steroids, and vitamins and minerals. It discusses what these dietary supplements are, how supplements are regulated, and the possible side effects of certain dietary supplements. The brochure offers guidelines for using dietary supplements, as well as several sources for reliable information on dietary supplements.
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “steroids” (or synonyms). The following was recently posted:
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Antenatal corticosteroids revisited: repeat courses Source: National Institute of Child Health and Human Development - Federal Government Agency [U.S.]; 2000 August 18; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2717&nbr=1943&a mp;string=steroids
•
Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants Source: American Academy of Pediatrics - Medical Specialty Society; 2002 February; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3175&nbr=2401&a mp;string=steroids
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Practice parameter: Steroids, acyclovir, and surgery for Bell’s palsy (an evidencebased review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2001 April; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2813&nbr=2039&a mp;string=steroids Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Anabolic Steroid Abuse Summary: This web site was launched as part of a public/private national multimedia public education initiative designed to alert the public to the dangers of anabolic steroids use. Source: National Institute on Drug Abuse, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5157
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Anabolic Steroids: A Threat to Mind and Body Source: National Institute on Drug Abuse, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3788
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Antenatal Corticosteroids Revisited: Repeat Courses Summary: This NIH consensus statement covers the benefits and risks of repeat courses of antenatal corticosteroids. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6338
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Tips For Teens About Steroids Summary: Steroids are used to treat certain diseases, but some people use them to enhance muscle mass and athletic performance. Source: National Clearinghouse for Alcohol and Drug Information, Center for Substance Abuse Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=939 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to steroids. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
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Associations and Steroids The following is a list of associations that provide information on and resources relating to steroids: •
Hormone Foundation Telephone: Toll-free: (800) 467-6663 Fax: (310) 941-0259 Email:
[email protected] Web Site: www.hormone.org Background: The Hormone Foundation is dedicated to serving as a resource for the public by promoting the prevention, treatment and cure of hormone-related diseases. It provides information on diseases including congenital adrenal hyperplasia, diabetes insipidus, hypoparathyroidism, hypothyroidism, polycystic ovary syndrome, and pseudohypoparathyroidism.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to steroids. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with steroids. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about steroids. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “steroids” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received
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your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “steroids”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “steroids” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “steroids” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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STEROIDS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 17-Ketosteroids: Steroids that contain a ketone group at position 17. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs.
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Cephalosporin antibiotics are derived from this genus. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually
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referred to as adolescence lie between 13 and 18 years of age. [NIH] Adolescent Behavior: Any observable response or action of an adolescent. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium
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cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [NIH] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Aldosterone Antagonists: Compounds which inhibit or antagonize the biosynthesis or actions of aldosterone. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH]
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Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Oxide: Al2O3. An oxide of aluminum, occurring in nature as various minerals such as bauxite, corundum, etc. It is used as an adsorbent, desiccating agent, and catalyst, and in the manufacture of dental cements and refractories. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH]
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Amblyopia: A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivationinduced amblopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. Strabismus and refractive errors may cause this condition. Toxic amblyopia is a disorder of the optic nerve which is associated with alcoholism, tobacco smoking, and other toxins and as an adverse effect of the use of some medications. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Neurotransmitters: Amino acids released by neurons as intercellular messengers. Among the amino acid neurotransmitters are glutamate (glutamic acid) and GABA which are, respectively, the most common excitatory and inhibitory neurotransmitters in the central nervous system. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic.
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Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU]
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Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Androstanes: The family of steroids from which the androgens are derived. [NIH] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Androstenes: Unsaturated derivatives of the steroid androstane containing at least one double bond at any site in any of the rings. [NIH] Anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin
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superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Ankle Joint: The joint that is formed by the inferior articular and malleolar articular surfaces of the tibia, the malleolar articular surface of the fibula, and the medial malleolar, lateral malleolar, and superior surfaces of the talus. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anthralin: An anti-inflammatory anthracene derivative used for the treatment of dermatoses, especially psoriasis. It may cause folliculitis. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on
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the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimony: A metallic element that has the atomic symbol Sb, atomic number 51, and atomic weight 121.75. It is used as a metal alloy and as medicinal and poisonous salts. It is toxic and an irritant to the skin and the mucous membranes. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphlogistic: An agent that counteracts inflammation and fever. [EU] Antiproliferative: Counteracting a process of proliferation. [EU]
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Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antithymocyte globulin: A protein used to reduce the risk of or to treat graft-versus-host disease. [NIH] Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aphthous Stomatitis: Inflammation of the mucous membrane of the mouth. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]
Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid
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to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arcus Senilis: A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatase inhibition: Prevention of the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibition is a type of hormone therapy used in postmenopausal women who have hormone-dependent breast cancer. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteritis: Inflammation of an artery. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU]
Dictionary 531
Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Asynchronous: Pacing mode where only one timing interval exists, that between the stimuli. While the duration of this interval may be varied, it is not modified by any sensed event once set. As no sensing occurs, the upper and lower rate intervals are the same as the pacema. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic Eczema: Generic term for acute or chronic inflammatory conditions of the skin, typically erythematous, edematous, papular, vesicular, and crusting; often accompanied by sensations of itching and burning. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH]
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Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Auditory Perception: The process whereby auditory stimuli are selected, organized and interpreted by the organism; includes speech discrimination. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Avian: A plasmodial infection in birds. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Azoospermia: Absence of spermatozoa in the semen, or failure of formation of spermatozoa. [EU]
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Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Balanitis: Inflammation of the glans penis. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Barotrauma: Injury following pressure changes; includes injury to the eustachian tube, ear drum, lung and stomach. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basilar Artery: The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by
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basic dyes. [NIH] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH]
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Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived
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constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
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Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Compounds: Inorganic or organic compounds that contain boron as an integral part of the molecule. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions),
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or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]
Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Neoplasms: Tumors or cancer of the breast. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH]
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Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calabar: The highly poisonous seed of a tropical African woody vine (Physostigma venenosum) used to produce contraction of the pupil of the eye and in tetanus and strychnine poisoning. It is the common ordeal bean employed by the natives in trials for witchcraft. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in
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T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Metabolism Disorders: Disorders in the processing of calcium in the body, including absorption, transport, storage, and utilization. [NIH] Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins. [NIH]
Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Canrenone: A synthetic pregnadiene compound with anti-aldosterone activity. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbogen: An inhalant of oxygen and carbon dioxide that increases the sensitivity of tumor cells to the effects of radiation therapy. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly-
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and heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardenolides: C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17. They are aglycone constituents of cardiac glycosides and must have at least one double bond in the molecule. the class includes cardadienolides and cardatrienolides. Members include digitoxin and digoxin and their derivatives and the strophanthins. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac Glycosides: Substances obtained from species of Digitalis, Strophanthus, and other plants that contain specific steroid glycosides or their semisynthetic derivatives and used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the Na(+)-K(+)-exchanging ATPase and they are often used in cell biological studies for that purpose. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green,
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leafy vegetables. May reduce the risk of developing cancer. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspases: A family of intracellular cysteine endopeptidases. They play a key role in inflammation and mammalian apoptosis. They are specific for aspartic acid at the P1 position. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral
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ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and
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adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrotendinous Xanthomatosis: A primary fatty degeneration of the cornea occurring physiologically as an arcus senilis. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical Ripening: A change in the cervix with respect to its readiness to relax. The cervix becomes softer, more flexible, more distensible, and shorter in the final weeks of pregnancy. Though naturally occurring during normal pregnancy, it can also be induced for certain cases of prolonged or high-risk pregnancy by administration of hormones. [NIH]
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Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [NIH] Cholenes: Unsaturated derivatives of cholane with methyl groups at C-10 and C-13 and a branched five-carbon chain at C-17. They must have at least one double bond in the ring system. [NIH] Choleretic: A choleretic agent. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially
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the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esterase: An enzyme that catalyzes the hydrolysis of cholesterol and some other sterol esters, to liberate cholesterol plus a fatty acid anion. EC 3.1.1.13. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus. [NIH]
Chorion: The outermost extraembryonic membrane. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronotherapy: The adaptation of the administration of drugs to circadian rhythms. The concept is based on the response of biological functions to time-related events, such as the
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low point in epinephrine levels between 10 p.m. and 4 a.m. or the elevated histamine levels between midnight and 4 a.m. The treatment is aimed at supporting normal rhythms or modifying therapy based on known variations in body rhythms. While chronotherapy is commonly used in cancer chemotherapy, it is not restricted to cancer therapy or to chemotherapy. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Circumcision: Excision of the prepuce or part of it. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clan: A small but distinctive community of subordinate importance, composed of densely aggregated individuals of one or a few species in climax-vegetation; frequently the result of vegetative propagation. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clenbuterol: A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH]
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Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clobetasol: Topical corticosteroid that is absorbed faster than fluocinonide. It is used in psoriasis, but may cause marked adrenocortical suppression. [NIH] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cochlear Duct: Spiral tube in the bony canal of the cochlea, lying on its outer wall between the scala vestibuli and scala tympani. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH]
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Coitus: Sexual intercourse. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Variable Immunodeficiency: Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections. [NIH] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the
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alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU]
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Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective tissue: The supporting or framework tissue of the animal body, formed of fibrous and ground substance with more or less numerous cells of various kinds. [NIH] Connective tissue: The supporting or framework tissue of the animal body, formed of fibrous and ground substance with more or less numerous cells of various kinds. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]
Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: Use of agents, devices, methods, or procedures which diminish the
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likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraceptive Agents: Chemical substances that prevent or reduce the probability of conception. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Contusion: A bruise; an injury of a part without a break in the skin. [EU] Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Copulation: Sexual contact of a male with a receptive female usually followed by emission of sperm. Limited to non-human species. For humans use coitus. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH]
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Corneal Neovascularization: New blood vessels originating from the corneal veins and extending from the limbus into the adjacent corneal stroma. These vessels may lie in the superficial and/or deep corneal stroma. Neovascularization is a sequel to numerous inflammatory diseases of the ocular anterior segment, including trachoma, viral interstitial keratitis, microbial keratoconjunctivitis, and the immune response elicited by corneal transplantation. [NIH] Corneal Stroma: The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes. [NIH] Corneal Transplantation: Partial or total replacement of the cornea from one human or animal to another. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH]
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Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] C-Peptide: A 31-amino acid peptide which connects the A and B chains of proinsulin. The exact composition of the peptide is species dependent. In beta cells proinsulin is enzymatically converted to insulin with the liberation of the C-peptide. An immunoassay has been developed for assessing pancreatic beta cell secretory function in diabetic patients in whom circulating insulin antibodies and exogenous insulin interfere with insulin immunoassay. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]
Critical Illness: A disease or state in which death is possible or imminent. [NIH] Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH] Croup: A condition characterized by resonant barking cough, hoarseness and persistant stridor and caused by allergy, foreign body, infection, or neoplasm. It occurs chiefly in infants and children. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective
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media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]
Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyanides: Inorganic salts of hydrogen cyanide containing the -CN radical. The concept also includes isocyanides. It is distinguished from nitriles, which denotes organic compounds containing the -CN radical. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein,
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cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytochrome b5: A cytochrome occurring in the endoplasmic reticulum that acts as an intermediate electron carrier in some reactions catalyzed by mixed function oxidases, e.g., fatty acid desaturation. It further activates molecular oxygen for an attack on the substrate. MW 16kDa. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daclizumab: A monoclonal antibody that is being studied for treatment of adult T-cell leukemia. Also called dacliximab. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH]
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Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dental Cements: Substances used as bonding or luting agents in restorative denistry, root canal therapy, prosthedontics, and orthodontics. [NIH] Dental Materials: Materials used in the production of dental bases, restorations, impressions, prostheses, etc. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of
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pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatologic Agents: Drugs used to treat or prevent skin disorders or for the routine care of skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Desogestrel: A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant
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and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diethylstilbestrol: DES. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH]
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Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diosgenin: (25R)-Spirost-5-en-3-beta-ol. A steroid sapogenin which is isolated from various plants. Can be converted to ecdysone, pregnenolone, and progesterone. Synonym: nitogenin. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disintegrins: A family of polypeptides purified from snake venoms, which contain the arginine-glycine-aspartic acid (RGD) sequence. The RGD tripeptide binds to integrin receptors and thus competitively inhibits normal integrin-ligand interactions. Disintegrins thus block adhesive functions and act as platelet aggregation inhibitors. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or
Dictionary 561
in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Doping: The action of administering a drug to someone before a sports event (originally to a horse before a race); the substance thus administered. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH]
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Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]
Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dydrogesterone: A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dyspnoea: Difficult or laboured breathing. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Dysuria: Painful or difficult urination. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectopic: Pertaining to or characterized by ectopia. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH]
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Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH]
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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emetic: An agent that causes vomiting. [EU] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enanthate: An oily injectable contraceptive given every 8 weeks. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into
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the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endolymphatic Duct: Duct connecting the endolymphatic sac with the membranous labyrinth. [NIH] Endolymphatic Sac: The blind pouch at the end of the endolymphatic duct. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components
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from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Enucleation: Removal of the nucleus from an eucaryiotic cell. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH]
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Epicondylitis: Inflammation of the epicondyle or of the tissues adjoining the epicondyle of the humerus. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Equalization: The reduction of frequency and/or phase distortion, or modification of gain and or phase versus frequency characteristics of a transducer, by the use of attenuation circuits whose loss or delay is a function of frequency. [NIH] Equilenin: 3-Hydroxyestra-1,3,5(10),6,8-pentaen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [NIH] Equilin: 3-Hydroxyestra-1,3,5(10)7-tetraen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring
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or atrophy. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromelalgia: Disease marked by paroxysmal, bilateral vasodilatation, particularly of the extremities, with burning pain, and increased skin temperature and redness. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Stricture: A narrowing of the esophagus often caused by acid flowing back from the stomach. This condition may require surgery. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]
Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH]
Dictionary 569
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Etomidate: Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic. [NIH]
Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excrete: To get rid of waste from the body. [NIH]
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Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]
Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]
Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expressed Sequence Tags: Sequence tags derived from cDNAs. Expressed sequence tags (ESTs) are partial DNA sequences from clones. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH]
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Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Facial: Of or pertaining to the face. [EU] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fertility Agents: Drugs used to increase fertility or to treat infertility. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and
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productivity. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Growth Retardation: The failure of a fetus to attain its expected growth potential at any gestational stage. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral,
Dictionary 573
anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. [NIH] Fluocinonide: A topical glucocorticoid used in the treatment of eczemas. [NIH] Fluocortolone: 6 alpha-Fluoro-11 beta,21-dihydroxy-16 alpha-methylpregna-1,4-diene-3,20diono. A topical glucocorticoid with anti-inflammatory activity used in the treatment of various skin disorders. It is used also as the acetate, caproate, and pivalate. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluoxymesterone: An anabolic steroid that has been used in the treatment of male hypogonadism, delayed puberty in males, and in the treatment of breast neoplasms in women. [NIH] Fluprednisolone: A synthetic glucocorticoid with anti-inflammatory properties. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH]
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Follicular Fluid: A fluid consisting of sex steroid hormones, plasma proteins, mucopolysaccharides, and electrolytes that is present in the vesicular ovarian follicle (Graafian follicle) surrounding the ovum. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized
Dictionary 575
connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
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Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestation period: The period of development of the young from the time of conception until birth. [NIH] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestrinone: A non-estrogenic contraceptive which is a weak progestin with strong antiprogesterone properties. It is effective if used once a week orally or can also be used in intravaginal devices. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in
Dictionary 577
any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a
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more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycocholic Acid: A bile salt that is usually used as the sodium salt. It is the glycine conjugate of cholic acid. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and choleretic. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Goniotomy: A surgical procedure for congenital glaucoma in which a sweeping incision is
Dictionary 579
made in the neshwork at the filtration angle by means of a knife-needle inserted through the opposite limbus and carried across the anterior chamber parallel to the iris. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasshoppers: Plant-eating orthopterans having hindlegs adapted for jumping. There are two main families: Acrididae and Romaleidae. Some of the more common genera are: Melanoplus, the most common grasshopper; Conocephalus, the eastern meadow grasshopper; and Pterophylla, the true katydid. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Cones: Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell
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survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hantavirus: A genus of the family Bunyaviridae causing Hantavirus infections, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. The genus has one recognized group (Hantaan group) consisting of several species including Dobrava-Belgrade virus, Seoul virus, Prospect Hill virus, Puumala virus, Thottapalayam virus, and Hantaan virus, the type species. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by
Dictionary 581
centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH]
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Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatoma: A liver tumor. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Hibernation: The dormant state in which some animal species pass the winter. It is characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. It is a natural physiological process in many warm-blooded animals. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of
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the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homosteroids: Steroids whose structure has been expanded by the addition of one or more carbon atoms to the ring skeleton in any of the four rings. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hyaline membrane disease: A respiratory disease of newborns, especially premature infants, in which a membrane composed of proteins and dead cells forms and lines the alveoli making gas exchange difficult or impossible. [NIH]
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Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic
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acid can result in impaired hydroxyproline formation. [NIH] Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains. [NIH] Hyperaldosteronism: Aldosteronism. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypopharynx: The portion of the pharynx between the inferior portion of the oropharynx and the larynx. [NIH] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic
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chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer
Dictionary 587
factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds,
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wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local
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infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH]
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Instar: The form of an insect during a particular stadium, i. e. any post-egg stage initiated or terminated by ecdysis. There are larval, nymphal, pupal, and adult instars; any larval stadium. [NIH] Instillation: . [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well
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as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Obstruction: Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anus. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH]
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Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of
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increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainate: Glutamate receptor. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide
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backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]
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Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Labyrinthitis: Inflammation of the inner ear. [NIH] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larva: Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leflunomide: An anticancer drug that works by inhibiting a cancer cell growth factor. Also called SU101. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended
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between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
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Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipoid: The most common nephrotic syndrome disease of childhood. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipomatosis: A disorder consisting of the accumulation of abnormal localized, or tumor-like fat in the tissues. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or
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cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term
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potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lordosis: The anterior concavity in the curvature of the lumbar and cervical spine as viewed from the side. The term usually refers to abnormally increased curvature (hollow back, saddle back, swayback). It does not include lordosis as normal mating posture in certain animals ( = posture + sex behavior, animal). [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lumpectomy: Surgery to remove the tumor and a small amount of normal tissue around it. [NIH]
Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells
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that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant meningioma: A rare, quickly growing tumor that occurs in the membranes that cover and protect the brain and spinal cord (meninges). [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malingering: Simulation of symptoms of illness or injury with intent to deceive in order to obtain a goal, e.g., a claim of physical illness to avoid jury duty. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammography: Radiographic examination of the breast. [NIH] Manic: Affected with mania. [EU]
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Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannans: Polysaccharides consisting of mannose units. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Maternal Behavior: The behavior patterns associated with or characteristic of a mother. [NIH]
Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized
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facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Meibomian: A series of simple, branched, alveolar, sebaceous glands, located in the tarso of the eyelids, whose ducts empty into the eyelid margins in line with and lateral to the lacrimal puncta. [NIH] Meibomian Glands: The sebaceous glands situated on the inner surface of the eyelids between the tarsal plates and conjunctiva. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melengestrol Acetate: A progestational hormone with reported glucocorticoid and antineoplastic activity. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Membranoproliferative: A disease that occurs primarily in children and young adults. Over time, inflammation leads to scarring in the glomeruli, causing proteinuria, hematuria, and sometimes chronic renal failure or end-stage renal disease. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menorrhagia: Excessive menstrual flow. [NIH]
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Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesoderm: The middle germ layer of the embryo. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metamorphosis: The ontogeny of insects, i. e. the series of changes undergone from egg, through larva and pupa, or through nymph, to adult. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the
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body to another. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [NIH] Methoxychlor: An insecticide. Methoxychlor has estrogenic effects in mammals, among other effects. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiological Techniques: Techniques used in microbiology. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU]
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Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mixed Function Oxidases: Catalyse the insertion of one oxygen atom of molecular oxygen into the organ substrate. Require a second substrate to donate electrons for the reduction of the second atom in the oxygen molecule to water. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Conformation: The characteristic three-dimensional shape of a molecule. [NIH]
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Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Morula: The early embryo at the developmental stage in which the blastomeres, resulting from repeated mitotic divisions of the fertilized ovum, form a compact mass. [NIH] Moths: Insects of the suborder Heterocera of the order Lepidoptera. [NIH] Motility: The ability to move spontaneously. [EU] Motor Endplate: The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief
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constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidose: Occurring in, or using multiple doses. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Fatigue: A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH]
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Mutagenic: Inducing genetic mutation. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Natural killer cells: NK cells. A type of white blood cell that contains granules with
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enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Neck Injuries: General or unspecified injuries to the neck. It includes injuries to the skin, muscles, and other soft tissues of the neck. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle Sharing: Usage of a single needle among two or more people for injecting drugs. Needle sharing is a high-risk behavior for contracting infectious disease. [NIH] Needlestick Injuries: Penetrating stab wounds caused by needles. They are of special concern to health care workers since such injuries put them at risk for developing infectious disease. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neonatologist: Doctor who specializes in treating the diseases and disorders of newborn babies. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH]
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Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]
Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH]
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Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nidation: Implantation of the conceptus in the endometrium. [EU] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-
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anginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from cyanides, which denotes inorganic salts of hydrogen cyanide. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Node-negative: Cancer that has not spread to the lymph nodes. [NIH] Nonmalignant: Not cancerous. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [NIH] Norsteroids: Steroids which have undergone contraction in ring size or reduction in side chains. [NIH] Novobiocin: An antibiotic drug used to treat infection. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH]
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Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Nymph: The immature stage in the life cycle of those orders of insects characterized by gradual metamorphosis, in which the young resemble the imago in general form of body, including compound eyes and external wings; also the 8-legged stage of mites and ticks that follows the first moult. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oestradiol: Growth hormone. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]
Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal
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organ via the vomeronasal nerve, is also included here. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Oophoritis: Inflammation of an ovary. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
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Optic cup: The white, cup-like area in the center of the optic disc. [NIH] Optic disc: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orchiectomy: The surgical removal of one or both testicles. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Organic Chemicals: A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form. [NIH] Organotin Compounds: Organic compounds which contain tin in the molecule. Used widely in industry and agriculture. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osmium Tetroxide: (T-4)-Osmium oxide (OsO4). A highly toxic and volatile oxide of osmium used in industry as an oxidizing agent. It is also used as a histological fixative and stain and as a synovectomy agent in arthritic joints. Its vapor can cause eye, skin, and lung damage. [NIH] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU]
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Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osmotic Fragility: Red blood cell sensitivity to change in osmotic pressure. When exposed to a hypotonic concentration of sodium in a solution, red cells take in more water, swell until the capacity of the cell membrane is exceeded, and burst. [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otitis Media with Effusion: Inflammation of the middle ear with a clear pale yellowcolored transudate. [NIH] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH]
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Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxandrolone: A synthetic hormone with anabolic and androgenic properties. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU]
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Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palliative therapy: Treatment given to relieve symptoms caused by advanced cancer. Palliative therapy does not alter the course of a disease but improves the quality of life. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancuronium: A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than curare but has less effect on the circulatory system and on histamine release. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness;
Dictionary 619
choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Par excellence: The petrous portion of the temporal bone, containing the inner ear and wedged in at the base of the skull between the sphenoid and occipital bones. [NIH] Paraesthesia: Morbid or perverted sensation; an abnormal sensation, as burning, prickling, formication, etc. [EU] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH]
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Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pedicle: Embryonic link between the optic vesicle or optic cup and the forebrain or diencephalon, which becomes the optic nerve. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentosan polysulfate: A drug used to relieve pain or discomfort associated with chronic inflammation of the bladder. It is also being evaluated for its protective effects on the gastrointestinal tract in people undergoing radiation therapy. [NIH] Pentostatin: A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [NIH]
Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves
Dictionary 621
peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peracetic Acid: A liquid that functions as a strong oxidizing agent. It has an acrid odor and is used as a disinfectant. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH]
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Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Periventricular Leukomalacia: Rare form of epilepsy. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Peroxisome Proliferators: A class of nongenotoxic carcinogens that induce the production of hepatic peroxisomes and induce hepatic neoplasms after long-term administration. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH]
Dictionary 623
Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [NIH] Phimosis: The inability to retract the foreskin over the glans penis due to tightness of the prepuce. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoric Acids: Inorganic derivatives of phosphoric acid (H3PO4). Inorganic salts are known as phosphates and organic esters are phosphoric acid esters. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH]
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Photoaffinity Labels: Biologically active molecules which are covalently bound to the enzymes or binding proteins normally acting on them. Binding occurs due to activation of the label by ultraviolet light. These labels are used primarily to identify binding sites on proteins. [NIH] Photochemotherapy: Therapy using oral or topical photosensitizing agents with subsequent exposure to light. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoperiod: The time period of daily exposure that an organism receives from daylight or artificial light. It is believed that photoperiodic responses may affect the control of energy balance and thermoregulation. [NIH] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other
Dictionary 625
nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to
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changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH]
Dictionary 627
Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU]
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Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Poultice: That made by mixing mustard and flour with water. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]
Pregnanes: Saturated derivatives of the steroid pregnane. The 5-beta series includes progesterone and related hormones; the 5-alpha series includes forms generally excreted in the urine. [NIH] Pregnanolone: A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties. [NIH]
Dictionary 629
Pregnenes: Unsaturated derivatives of pregnanes. [NIH] Pregnenolone: Steroid hormone. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary central nervous system lymphoma: Cancer that arises in the lymphoid tissue found in the central nervous system (CNS). The CNS includes the brain and spinal cord. [NIH]
Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Proestrus: Phase of the estrous cycle preceding estrus during which the Graafian follicle undergoes maturation. Applies to animals. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed.
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When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]
Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in
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the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatic Neoplasms: Tumors or cancer of the prostate. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH]
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Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychoneuroimmunology: The field concerned with the interrelationship between the brain, behavior and the immune system. Neuropsychologic, neuroanatomic and psychosocial studies have demonstrated their role in accentuating or diminishing immune/allergic responses. [NIH] Psychotomimetic: Psychosis miming. [NIH]
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Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Sarcoidosis: A disease of unknown etiology characterized by tuberclelike, granulomatous nodules which may affect the skin, the lungs, the lymph nodes, the bones of the distal extremities, the conjunctiva, the lacrimal gland, the retina and the uveal tract. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupa: An inactive stage between the larval and adult stages in the life cycle of insects. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU]
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Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical mastectomy: Surgery for breast cancer in which the breast, chest muscles, and all of the lymph nodes under the arm are removed. For many years, this was the operation most used, but it is used now only when the tumor has spread to the chest muscles. Also called the Halsted radical mastectomy. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]
Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a
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cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Glutamate: Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases. [NIH]
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Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH]
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Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by
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specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrobulbar: Behind the pons. [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue
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structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhythmicity: Regular periodicity. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk-Taking: Undertaking a task involving a challenge for achievement or a desirable goal in which there is a lack of certainty or a fear of failure. It may also include the exhibiting of certain behaviors whose outcomes may present a risk to the individual or to those associated with him or her. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH]
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Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scalpel: A small pointed knife with a convex edge. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schematic: Representative or schematic eye computed from the average of a large number of human eye measurements by Allvar Gullstrand. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Schwannoma: A tumor of the peripheral nervous system that begins in the nerve sheath (protective covering). It is almost always benign, but rare malignant schwannomas have been reported. [NIH] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH]
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Sebaceous gland: Gland that secretes sebum. [NIH] Seborrhea: Hypersecretion of sebum with excessive oily secretion from the sweat glands. [NIH]
Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secosteroids: Steroids in which fission of one or more ring structures and concomitant addition of a hydrogen atom at each terminal group has occurred. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH]
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Selenious Acid: A selenium compound used as a source of selenium, especially for patients that develop selenium deficiency following prolonged parenteral nutrition. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous Epithelium: Specialized epithelium lining the seminiferous tubules containing developing and mature spermatozoa and Sertoli cells. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone
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tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Behavior: Sexual activities of humans. [NIH] Sex Behavior, Animal: Sexual activities of animals. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Differentiation: Differentiation of male and female tissues and organs during embryogenesis, but after sex determination (sex determination (genetics)). [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Shoulder Pain: Unilateral or bilateral pain of the shoulder. It is often caused by physical activities such as work or sports participation, but may also be pathologic in origin. [NIH] Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH]
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Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silanes: Compounds similar to hydrocarbons in which a tetravalent silicon atom replaces the carbon atom. They are very reactive, ignite in air, and form useful derivatives. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicosis: A type of pneumoconiosis caused by inhalation of particles of silica, quartz, ganister or slate. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Sitosterols: A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]
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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [NIH] Snake Venoms: Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors. [NIH] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Acetate: The trihydrate sodium salt of acetic acid, which is used as a source of sodium ions in solutions for dialysis and as a systemic and urinary alkalizer, diuretic, and expectorant. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft Tissue Injuries: Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as "soft tissue injuries of the hand". [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Songbirds: Passeriformes of the suborder, Oscines, in which the flexor tendons of the toes are separate, and the lower syrinx has 4 to 9 pairs of tensor muscles inserted at both ends of the tracheal half rings. They include many commonly recognized birds such as crows, finches, robins, sparrows, and swallows. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH]
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Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sperm Count: A count of sperm in the ejaculum, expressed as number per milliliter. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Compression: Acute and chronic conditions characterized by external mechanical compression of the spinal cord due to extramedullary neoplasm; epidural abscess; spinal fractures; bony deformities of the vertebral bodies; and other conditions. Clinical manifestations vary with the anatomic site of the lesion and may include localized pain, weakness, sensory loss, incontinence, and impotence. [NIH] Spinal Fractures: Broken bones in the vertebral column. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal
Dictionary 647
nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sports Medicine: The field of medicine concerned with physical fitness and the diagnosis and treatment of injuries sustained in sports activities. [NIH] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Stagnation: The slowing down or stoppage of the flowing of any fluid. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stanozolol: Anabolic agent. [NIH] Staphylococcal Scalded Skin Syndrome: A disease of infants due to group 2 phage type 17 staphylococci that produce an epidermolytic exotoxin. Superficial fine vesicles and bullae form and rupture easily, resulting in loss of large sheets of epidermis. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Status Asthmaticus: A sudden intense and continuous aggravation of a state of asthma, marked by dyspnea to the point of exhaustion and collapse and not responding to the usual
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therapeutic efforts. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by
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inhibiting the initiation and elongation processes during protein synthesis. [NIH] Streptozocin: An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress urinary: Leakage of urine caused by actions--such as coughing, laughing, sneezing, running, or lifting--that place pressure on the bladder from inside the body. Stress urinary incontinence can result from either a fallen bladder or weak sphincter muscles. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Stria Vascularis: A layer of highly vascular pigmented granular cells on the outer wall of the cochlear duct. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Strophanthins: A number of different cardioactive glycosides obtained from Strophanthus species. ouabain is from S. gratus and cymarine from S. kombe. They are used like the digitalis glycosides. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU]
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Subcutaneous: Beneath the skin. [NIH] Subfornical Organ: A structure, situated close to the intraventricular foramen, which induces drinking behavior after stimulation with angiotensin II. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submucous: Occurring beneath the mucosa or a mucous membrane. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Subtrochanteric: Below a trochanter. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Supraoptic Nucleus: Hypothalamic nucleus overlying the beginning of the optic tract. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue.
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[NIH]
Surgical castration: Surgical removal of the testicles (orchiectomy) or ovaries (oophorectomy) to stop the production of sex hormones. Decreasing the levels of hormones may stop the growth of certain cancers. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of
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their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synthetic retinoid: A substance related to vitamin A that is produced in a laboratory. [NIH] Syrinx: A fistula. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talc: A native magnesium silicate. [NIH] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tamponade: The inserting of a tampon; a dressing is inserted firmly into a wound or body cavity, as the nose, uterus or vagina, principally for stopping hemorrhage. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Tellurium: Tellurium. An element that is a member of the chalcogen family. It has the atomic symbol Te, atomic number 52, and atomic weight 127.60. It has been used as a coloring agent and in the manufacture of electrical equipment. Exposure may cause nausea, vomiting, and CNS depression. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU]
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Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetravalent: Pertaining to a group of 4 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by
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the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thymus Gland: A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH]
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Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tilapia: A freshwater fish used as an experimental organism and for food. This genus of the family Cichlidae inhabits Central and South America (one species extends north into Texas), West Indies, Africa, Madagascar, Syria, and coastal India. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tin Compounds: Inorganic compounds that contain tin as an integral part of the molecule. [NIH]
Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tome: A zone produced by a number of irregular spaces contained in the outermost layer of denture of the root of a tooth. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures
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preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torpor: State of mental and motor inactivity with partial insensibility, stagnation of function, without losing consciousness. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trabecular Meshwork: A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm. [NIH] Trabeculectomy: Any surgical procedure for treatment of glaucoma by means of puncture or reshaping of the trabecular meshwork. It includes goniotomy, trabeculotomy, and laser perforation. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Trachoma: A chronic infection of the conjunctiva and cornea caused by Chlamydia trachomatis. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH]
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Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transforming Growth Factor alpha: Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to epidermal growth factor and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
Transforming Growth Factors: Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, transforming growth factor alpha and transforming growth factor beta. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Triamcinolone Acetonide: An esterified form of triamcinolone. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions. [NIH]
Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left
658 Steroids
heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trophic: Of or pertaining to nutrition. [EU] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tropoelastin: A salt-soluble precursor of elastin. Lysyl oxidase is instrumental in converting it to elastin in connective tissue. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]
Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Lysis Syndrome: A syndrome resulting from cytotoxic therapy, occurring generally in aggressive, rapidly proliferating lymphoproliferative disorders. It is characterized by combinations of hyperuricemia, lactic acidosis, hyperkalemia, hyperphosphatemia and hypocalcemia. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH]
Dictionary 659
Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultraviolet Therapy: The use of ultraviolet electromagnetic radiation in the treatment of disease, usually of the skin. This is the part of the sun's spectrum that causes sunburn and tanning. Ultraviolet A, used in PUVA, is closer to visible light and less damaging than Ultraviolet B, which is ionizing. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Uncompetitive: A type of enzyme inhibition that arises when the inhibitor cannot combine with the free enzyme, but is capable of combining only with the substrate-enzyme complex. [NIH]
Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
660 Steroids
Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamics: The mechanical laws of fluid dynamics as they apply to urine transport. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Varicella: Chicken pox. [EU] Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH]
Dictionary 661
Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]
Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH]
662 Steroids
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virilism: Development of masculine traits in the female. [NIH] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the
Dictionary 663
tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visceral fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH]
664 Steroids
White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zona Fasciculata: The wide middle zone of the adrenal cortex. This zone consists of large lipid-laden cells radially arranged in parallel cords. It converts pregnenolone to cortisol by a series of enzymatically regulated steps. A small amount of corticosterone is formed as a byproduct of cortisol synthesis. [NIH] Zona Reticularis: The inner zone of the adrenal cortex. This zone consists of an anastomosing network of cells which resemble those of the zona fasciculata except for the fact that they contain less lipid. The mitochondria are elongated and contain a mixture of
Dictionary 665
tubular and flattened cristae. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
667
INDEX 1 17-Ketosteroids, 383, 519 A Abdomen, 307, 313, 519, 536, 537, 567, 591, 595, 598, 618, 622, 638, 647, 648, 654, 660, 663 Abdominal fat, 519, 663 Abdominal Pain, 95, 305, 519, 575, 593, 659 Aberrant, 90, 519 Ablation, 95, 235, 426, 519 Abscess, 470, 519, 642, 646 Acantholysis, 519, 620 Acceptor, 519, 597, 617, 631, 650 Acetaldehyde, 519, 522 Acetone, 378, 379, 519, 594 Acetylcholine, 58, 76, 113, 127, 211, 519, 546, 612 Acidosis, 368, 519, 658 Acne, 180, 241, 276, 332, 362, 389, 506, 519, 555, 662 Acne Vulgaris, 332, 362, 389, 519 Acoustic, 18, 519, 532, 662 Acremonium, 519, 544 Acrylonitrile, 330, 520, 639 Actin, 77, 520, 608 Action Potentials, 22, 520 Activities of Daily Living, 15, 520 Acute lymphoblastic leukemia, 275, 304, 520 Acute lymphocytic leukemia, 520 Acute renal, 161, 225, 520, 581 Acyclovir, 132, 222, 507, 520, 574 Acyl, 520, 568 Adaptability, 520, 543, 544 Adaptation, 70, 301, 520, 546, 607, 625 Adduct, 157, 353, 356, 380, 520 Adenosine, 520, 539, 620, 623, 653 Adenosine Deaminase, 520, 620 Adhesives, 520 Adipocytes, 114, 520, 596 Adipose Tissue, 78, 150, 519, 520 Adjustment, 104, 520 Adolescence, 78, 256, 520 Adolescent Behavior, 102, 521 Adoptive Transfer, 112, 521 Adrenal Cortex, 22, 117, 156, 243, 521, 522, 526, 553, 568, 584, 585, 613, 629, 637, 664
Adrenal Glands, 63, 101, 117, 370, 391, 505, 521, 525 Adrenal insufficiency, 6, 101, 218, 521 Adrenal Medulla, 521, 542, 567, 612 Adrenergic, 521, 522, 561, 566, 567, 651, 659 Adverse Effect, 7, 31, 33, 46, 110, 146, 197, 521, 524, 644, 662 Aerobic, 21, 233, 521, 570, 605, 617 Aerobic Exercise, 21, 521 Aerobic Metabolism, 521, 617 Aerobic Respiration, 521, 617 Aerosol, 521, 534, 662 Afferent, 14, 26, 72, 73, 95, 521, 596, 615, 647 Affinity Chromatography, 61, 117, 521 Agar, 521, 555, 625 Age of Onset, 522, 659 Ageing, 413, 522 Aggravation, 522, 647 Aggressiveness, 80, 505, 522 Agonist, 13, 57, 72, 113, 274, 367, 425, 522, 548, 561, 566, 608, 611, 635, 652 Air Sacs, 522, 523 Airway, 24, 36, 55, 76, 133, 138, 159, 161, 170, 184, 253, 522, 538, 644, 663 Albumin, 211, 431, 522, 625 Albuterol, 55, 522 Alcohol Dehydrogenase, 241, 522 Aldehydes, 328, 400, 522 Aldosterone, 42, 47, 106, 162, 201, 229, 386, 427, 433, 522, 540, 605 Aldosterone Antagonists, 201, 386, 522 Alendronate, 479, 522 Alertness, 522, 539 Algorithms, 522, 536 Alimentary, 231, 523, 566, 619, 621 Alkaline, 29, 347, 348, 405, 410, 519, 523, 524, 540, 617, 653 Alkaline Phosphatase, 29, 405, 410, 523 Alkaloid, 523, 548, 606, 611, 649, 653 Alkylating Agents, 9, 523 Alkylation, 329, 365, 523 Alleles, 92, 523 Allergen, 55, 85, 138, 139, 333, 523, 642 Allergic Rhinitis, 80, 182, 192, 218, 248, 253, 257, 264, 276, 523, 539 Allogeneic, 170, 228, 523, 579, 581
668 Steroids
Allograft, 83, 146, 161, 523 Allylamine, 523, 524 Alopecia, 255, 256, 276, 332, 362, 430, 523, 555 Alpha Particles, 523, 634 Alternative medicine, 481, 523 Alternative Splicing, 523, 631 Aluminum, 434, 523 Aluminum Oxide, 434, 523 Alveoli, 55, 71, 523, 583, 661 Amblyopia, 148, 221, 264, 524 Amebiasis, 524, 604 Ameliorated, 38, 524 Amenorrhea, 276, 524, 527, 626 Amine, 348, 353, 370, 378, 381, 389, 404, 524, 583 Amino Acid Motifs, 524, 551 Amino Acid Neurotransmitters, 68, 108, 524 Amino Acid Sequence, 524, 526, 527, 534, 551, 576, 630, 643 Amino Acid Substitution, 109, 524 Ammonia, 348, 376, 520, 524, 578, 651, 659 Amnion, 524, 546 Amniotic Fluid, 255, 524 Amphetamine, 46, 524, 535, 558 Amplification, 73, 274, 407, 525 Ampulla, 525, 545, 565, 571 Amygdala, 65, 104, 114, 525, 533, 597, 653 Amyloid, 28, 39, 193, 525 Amyloidosis, 148, 227, 525 Anaesthesia, 129, 192, 525, 588 Anaesthetic, 337, 338, 525 Anal, 167, 448, 525, 573, 598 Analgesic, 72, 525, 559, 586, 606, 614 Analog, 32, 35, 520, 525, 573, 574, 595, 596 Analogous, 36, 73, 525, 626, 657 Anaphylactic, 28, 525 Anaphylatoxins, 525, 550 Anaphylaxis, 276, 525 Anatomical, 18, 44, 84, 93, 94, 95, 99, 525, 531, 551, 560, 587, 606, 610, 619, 640 Androgen-Binding Protein, 526, 643 Androstanes, 341, 454, 526 Androstenedione, 79, 285, 322, 327, 330, 363, 397, 526 Androstenes, 329, 371, 393, 394, 395, 526 Anecdotal report, 307, 526 Anemia, 276, 498, 526, 534, 581, 607, 653 Anesthesia, 81, 82, 110, 173, 198, 230, 259, 314, 446, 522, 526, 555, 563, 610
Anesthetics, 6, 57, 58, 82, 328, 447, 484, 526, 533, 567 Aneurysm, 526, 661 Anginal, 526, 612 Angiogenesis, 78, 119, 217, 242, 339, 340, 343, 364, 375, 526, 565, 601 Angiogenesis inhibitor, 78, 526, 565 Angiogram, 83, 526 Angiotensin converting enzyme inhibitor, 173, 526 Angiotensin-Converting Enzyme Inhibitors, 43, 526 Angiotensinogen, 42, 526, 637 Animal model, 13, 18, 28, 37, 40, 44, 92, 108, 111, 116, 118, 527 Anions, 522, 527, 592, 643 Anisotropy, 527, 573 Ankle, 37, 257, 527 Ankle Joint, 37, 527 Annealing, 527, 627 Anomalies, 227, 264, 527, 653 Anorexia, 27, 220, 527, 575 Anorexia Nervosa, 27, 220, 527 Anovulation, 90, 527, 626 Antagonism, 30, 157, 174, 429, 447, 527, 539, 653 Antecedent, 527 Anthralin, 444, 527 Antiallergic, 527, 553 Antiandrogens, 181, 527 Antibacterial, 433, 527, 646 Antibiotic, 12, 80, 312, 527, 532, 538, 568, 612, 620, 627, 646, 648, 649 Antibody therapy, 112, 309, 528 Anticholinergic, 367, 528 Anticoagulant, 528, 631 Anticonvulsant, 110, 528 Antidepressant, 115, 446, 528, 539, 573 Antidote, 528, 573 Antiepileptic, 22, 528 Antifungal, 6, 361, 528, 593, 604 Antifungal Agents, 361, 528 Antigen-Antibody Complex, 528, 549 Anti-infective, 528, 545, 584, 592 Anti-Inflammatory Agents, 325, 332, 370, 378, 379, 386, 399, 420, 528, 553 Antimetabolite, 520, 528, 538, 573 Antimicrobial, 433, 528, 547 Antimony, 360, 528 Antineoplastic, 400, 401, 523, 528, 538, 553, 555, 573, 602, 604, 620, 626, 649
Index 669
Antineoplastic Agents, 400, 401, 523, 528, 620 Antioxidant, 113, 528, 617 Antiphlogistic, 427, 528 Antiproliferative, 149, 209, 528 Antipyretic, 529, 559 Antiseptic, 519, 529, 542 Antiserum, 529, 554 Antithymocyte globulin, 248, 529 Antitumour, 369, 529 Antiviral, 23, 312, 520, 529, 538, 587, 590 Anuria, 529, 594 Anus, 525, 529, 537, 566, 591, 621 Anxiety Disorders, 27, 206, 342, 529, 619 Anxiolytic, 32, 110, 342, 529 Aorta, 529, 541, 661 Aphthous Stomatitis, 361, 529 Aplasia, 228, 529 Aplastic anemia, 204, 228, 529 Apnea, 529 Apolipoproteins, 529, 598 Apoptosis, 31, 58, 60, 62, 88, 117, 155, 183, 199, 203, 529, 542 Applicability, 425, 529 Approximate, 79, 529 Arachidonate 12-Lipoxygenase, 529, 598 Arachidonate 15-Lipoxygenase, 529, 598 Arachidonate Lipoxygenases, 530, 598 Arachidonic Acid, 11, 529, 530, 555, 563, 596, 630 Arcus Senilis, 530, 544 Arginine, 14, 311, 525, 530, 560, 612, 660 Aromatase, 32, 45, 116, 201, 248, 251, 330, 410, 530 Aromatase inhibition, 248, 530 Arrhythmia, 530, 662 Arterial, 51, 71, 136, 162, 219, 257, 523, 530, 538, 546, 552, 585, 632, 652 Arteries, 51, 119, 529, 530, 533, 536, 544, 553, 599, 604, 608, 626, 633, 654, 659 Arteriolar, 530, 537, 637 Arterioles, 530, 536, 540, 604, 661 Arteriolosclerosis, 530 Arteriosclerosis, 311, 339, 340, 343, 364, 376, 530 Arteritis, 155, 214, 530, 627 Arthroscopy, 191, 530 Articular, 37, 190, 191, 527, 530, 616, 657 Aseptic, 307, 530, 615, 648 Aspartate, 72, 126, 531, 635 Aspartic, 531, 542, 560, 565, 569 Aspartic Acid, 531, 542, 560
Aspergillosis, 171, 225, 531, 593 Aspiration, 368, 531 Assay, 12, 17, 34, 58, 109, 346, 355, 411, 421, 438, 531, 587, 634 Astringent, 531, 542 Astrocytes, 98, 107, 531, 606 Astrocytoma, 531, 576 Asymptomatic, 55, 138, 145, 475, 524, 531, 534, 582 Asynchronous, 220, 531 Ataxia, 498, 531, 584, 653 Atmospheric Pressure, 167, 531 Atopic, 83, 126, 139, 146, 158, 186, 247, 252, 531 Atopic Eczema, 126, 531 Atrial, 531, 552, 657 Atrioventricular, 531, 552 Atrium, 531, 541, 552, 653, 657, 661 Atrophy, 15, 99, 370, 497, 498, 519, 531, 568, 610 Attenuated, 46, 79, 122, 532, 560 Attenuation, 532, 567 Atypical, 184, 275, 447, 532 Auditory, 18, 26, 142, 532, 569, 601, 660 Auditory nerve, 532, 601 Auditory Perception, 18, 532 Autacoids, 532, 588 Autoimmune disease, 43, 45, 99, 106, 532, 607, 624, 625 Autoimmune Hepatitis, 235, 532 Autoimmunity, 532 Autologous, 188, 532, 581 Autologous bone marrow transplantation, 532, 581 Autonomic, 27, 519, 532, 612, 621, 647, 651 Autonomic Nervous System, 532, 621, 651 Autopsy, 86, 532 Autoradiography, 65, 103, 532 Autosuggestion, 532, 586 Avian, 26, 70, 532 Axillary, 143, 372, 393, 394, 395, 532 Axonal, 68, 75, 532, 664 Axons, 350, 532, 557, 559, 579, 591, 615, 621, 633, 638, 647 Azithromycin, 234, 532 Azoospermia, 237, 532 B Bacillus, 239, 384, 533, 538, 627, 658 Bacterial Infections, 533, 549 Bacterial Physiology, 520, 533 Bactericidal, 533, 569 Bacteriophage, 533, 625, 656
670 Steroids
Bacteriostatic, 533, 568 Bacterium, 533, 551, 581 Bacteriuria, 533, 660 Balanitis, 9, 533 Barbiturate, 533, 552 Barotrauma, 33, 533 Basal Ganglia, 65, 531, 533, 537, 575, 577, 597, 613 Basal Ganglia Diseases, 531, 533 Base, 43, 74, 93, 329, 378, 382, 402, 533, 557, 576, 593, 594, 619, 633, 652 Basement Membrane, 339, 340, 343, 364, 375, 533, 570, 595 Basilar Artery, 533, 601 Basophils, 533, 579, 596 Beclomethasone, 149, 402, 471, 534 Benign prostatic hyperplasia, 86, 323, 327, 362, 363, 407, 430, 534, 572 Benign tumor, 534, 595 Benzene, 326, 345, 349, 390, 534 Benzodiazepines, 32, 534, 573 Benzoic Acid, 326, 347, 534 Benzyl Alcohol, 352, 534 Beta-Endorphin, 97, 161, 534 Beta-pleated, 525, 534 Beta-Thalassemia, 154, 534 Bilateral, 53, 129, 140, 354, 534, 567, 568, 619, 626, 643 Bile Acids, 247, 398, 399, 534, 648, 650, 652 Bile Acids and Salts, 534 Bile Ducts, 534, 535, 574 Bile Pigments, 535, 593 Biliary, 181, 535, 545 Bilirubin, 522, 535, 574, 577, 585 Binding agent, 354, 535 Binding Sites, 81, 114, 535, 624 Bioassay, 140, 263, 535 Bioavailability, 42, 140, 535 Bioavailable, 42, 535 Biodegradation, 535 Bioengineering, 492, 535 Biogenic Amines, 453, 464, 535 Biological Factors, 74, 535 Biological response modifier, 535, 590 Biological therapy, 535, 580 Biological Transport, 535, 559 Biomarkers, 19, 535 Biopsy, 8, 48, 60, 83, 119, 221, 234, 307, 310, 313, 446, 535, 621 Biosynthesis, 40, 107, 109, 121, 122, 126, 128, 174, 196, 265, 341, 415, 453, 468, 476, 522, 530, 535, 631, 643, 658, 660
Biotechnology, 105, 120, 128, 466, 467, 481, 493, 496, 497, 498, 499, 535 Biotin, 268, 536, 614 Biotransformation, 4, 31, 536, 622 Biphasic, 292, 536 Bladder, 412, 445, 534, 536, 555, 588, 592, 607, 620, 631, 649, 659, 660 Blastocyst, 536, 550, 564, 617, 625, 658 Blastomycosis, 536, 593 Blister, 536, 620 Bloating, 536, 588, 593 Blood Cell Count, 313, 536, 581 Blood Coagulation, 536, 540, 654 Blood Glucose, 6, 8, 312, 313, 314, 536, 581, 590 Blood Platelets, 536, 643, 654 Blood pressure, 5, 8, 21, 42, 154, 259, 310, 482, 536, 541, 585, 606, 612, 633, 645 Blood-Brain Barrier, 53, 536, 596 Blot, 29, 51, 76, 119, 536, 587, 614 Blotting, Western, 537, 587 Body Composition, 24, 79, 146, 234, 239, 537 Body Fluids, 402, 535, 537, 562, 573, 613, 645, 658 Body Mass Index, 152, 196, 206, 537 Bone Density, 21, 34, 316, 441, 444, 480, 537 Bone Resorption, 11, 537 Bone scan, 225, 537, 640 Boron, 268, 405, 537, 555 Boron Compounds, 405, 537 Boron Neutron Capture Therapy, 537 Bowel Movement, 537, 559, 648 Brachiocephalic Veins, 537, 650 Brachytherapy, 537, 591, 593, 634, 664 Bradykinin, 537, 612, 625 Brain Hypoxia, 537, 538, 653 Brain Infarction, 537, 538 Brain Injuries, 69, 538 Brain Ischemia, 53, 538 Brain metastases, 81, 538 Brain Stem, 537, 538, 544, 552 Branch, 89, 121, 515, 538, 556, 563, 600, 601, 611, 614, 620, 622, 633, 646, 653 Breakdown, 538, 559, 575 Breast Neoplasms, 538, 573 Breeding, 26, 93, 357, 538 Broad-spectrum, 538, 544 Bromine, 331, 386, 397, 429, 538 Bromodeoxyuridine, 38, 538 Bronchi, 538, 539, 567, 570, 601, 653, 656
Index 671
Bronchial, 71, 157, 165, 186, 254, 273, 368, 467, 479, 538, 583, 631, 653 Bronchiectasis, 188, 215, 538 Bronchioles, 523, 538 Bronchiolitis, 80, 83, 210, 238, 538 Bronchiseptica, 538, 622 Bronchitis, 184, 277, 538, 546 Bronchoconstriction, 76, 165, 368, 538 Bronchodilator, 538, 547 Bronchopulmonary, 33, 70, 225, 314, 538 Bronchopulmonary Dysplasia, 33, 314, 538 Bronchospasm, 368, 539 Bronchus, 245, 538, 539 Buccal, 539, 599, 648 Budesonide, 4, 142, 146, 149, 166, 213, 469, 472, 539 Bulimia, 220, 539 Bullous, 231, 253, 539 Bupropion, 190, 539 Burns, 235, 396, 539 Burns, Electric, 539 Butyric Acid, 32, 346, 539 C Cachexia, 34, 539 Caffeine, 539, 633 Calabar, 373, 385, 539 Calcification, 530, 539 Calcineurin, 43, 193, 234, 539 Calcium channel blocker, 540, 662 Calcium Channels, 540 Calcium Metabolism Disorders, 400, 540 Calcium Signaling, 20, 62, 540 Callus, 540, 564 Calmodulin, 539, 540 Candidiasis, 7, 131, 212, 447, 540 Candidosis, 187, 447, 540 Canrenone, 156, 540 Capillary, 71, 143, 201, 339, 340, 343, 364, 365, 376, 537, 540, 577, 661, 662 Capsules, 434, 540, 575, 577 Carbogen, 245, 540 Carbohydrate, 40, 161, 422, 540, 553, 577, 578, 627 Carbon Dioxide, 131, 540, 541, 557, 573, 575, 625, 637, 661 Carboxy, 322, 345, 392, 541 Carboxylic Acids, 334, 369, 388, 393, 541 Carcinogen, 520, 541, 568, 604 Carcinogenesis, 80, 108, 169, 170, 229, 416, 541, 545
Carcinogenic, 412, 523, 534, 541, 589, 614, 630, 648 Carcinoma, 77, 232, 245, 323, 327, 363, 412, 541, 555 Cardenolides, 326, 541 Cardiac Glycosides, 459, 541 Cardiac Output, 119, 368, 541, 649 Cardiopulmonary, 163, 195, 223, 368, 541 Cardiopulmonary Bypass, 163, 195, 223, 541 Cardiorespiratory, 234, 521, 541 Cardiotonic, 21, 131, 143, 167, 262, 541, 560 Cardiovascular disease, 42, 119, 200, 413, 421, 422, 541 Cardiovascular System, 368, 429, 434, 438, 458, 459, 541, 569 Carotene, 541, 638 Carotenoids, 190, 451, 541 Carpal Tunnel Syndrome, 130, 277, 542 Carrier Proteins, 542, 625, 634 Case report, 137, 139, 144, 192, 198, 228, 252, 255, 542, 547 Case series, 542, 547 Caspases, 31, 60, 542 Castration, 88, 411, 426, 542 Catabolism, 426, 542 Catalytic Domain, 542 Cataract, 251, 375, 478, 542 Catechol, 542 Catecholamine, 78, 103, 542, 561 Catheterization, 542, 592 Catheters, 30, 542, 588, 591 Cations, 542, 592 Cauda Equina, 542, 640 Caudal, 198, 542, 559, 586, 613, 627 Caudate Nucleus, 45, 533, 542, 609, 613 Causal, 90, 221, 543, 591 Cause of Death, 42, 494, 543 Caveolae, 20, 543 Caveolins, 543 Cell Adhesion, 118, 439, 543, 590 Cell Adhesion Molecules, 439, 543 Cell Aggregation, 543, 617 Cell Count, 145, 543 Cell Cycle, 31, 43, 71, 155, 199, 411, 461, 543, 547, 555, 569, 661 Cell Death, 52, 60, 62, 105, 529, 543, 569, 576, 609 Cell Differentiation, 117, 543, 644 Cell Division, 412, 497, 533, 543, 556, 569, 579, 602, 603, 605, 625, 630, 641
672 Steroids
Cell Membrane Structures, 543 Cell motility, 543, 582 Cell proliferation, 50, 52, 412, 417, 530, 543, 591, 644 Cell Respiration, 521, 543, 605, 617, 637 Cell Size, 543 Cell Survival, 38, 543, 580 Cell Transplantation, 313, 314, 544 Cellobiose, 544 Cellulose, 6, 544, 574, 625 Centrifugation, 544, 581, 604 Cephalosporins, 468, 544 Ceramide, 544 Cerebellar, 67, 431, 531, 544, 636 Cerebellum, 15, 538, 544, 574, 636 Cerebral, 53, 91, 119, 129, 136, 179, 249, 531, 533, 536, 537, 538, 544, 552, 567, 569, 572, 574, 577, 584, 605, 632, 633, 646, 652, 654 Cerebral Arteries, 119, 249, 533, 544, 605 Cerebral hemispheres, 533, 537, 538, 544, 577, 652 Cerebrospinal, 28, 53, 544, 546, 584, 599, 647 Cerebrospinal fluid, 28, 53, 544, 546, 584, 599, 647 Cerebrotendinous Xanthomatosis, 544 Cerebrovascular, 53, 119, 533, 541, 544, 653 Cerebrum, 544, 624, 652, 658 Cervical, 86, 112, 144, 222, 230, 544, 599, 601 Cervical Ripening, 222, 544 Cervix, 544, 545, 637 Character, 350, 545, 557 Chemoprevention, 108, 545 Chemopreventive, 35, 545 Chemoprotective, 12, 545 Chemotactic Factors, 545, 550 Chemotaxis, 28, 545 Chenodeoxycholic Acid, 386, 545 Chickenpox, 171, 545 Chimeras, 57, 109, 112, 545 Chimeric Proteins, 63, 545 Chlorhexidine, 6, 545 Chloride Channels, 82, 545 Chlorine, 331, 386, 397, 545 Chlorophyll, 545, 574 Cholangitis, 158, 545 Cholecalciferol, 376, 398, 405, 545 Cholenes, 329, 545 Choleretic, 545, 558, 578, 598
Cholestasis, 545 Cholesterol Esterase, 64, 546 Cholesterol Esters, 64, 546, 598 Cholic Acid, 326, 373, 385, 546, 578 Choline, 112, 546 Cholinergic, 546, 606, 611 Chorioamnionitis, 181, 234, 546 Chorion, 546 Choroid, 53, 546, 638, 660 Choroid Plexus, 53, 546 Chromaffin System, 546, 565 Chromatin, 49, 529, 546, 646 Chromium, 268, 377, 546 Chromosomal, 19, 89, 92, 525, 546, 576, 638, 640 Chromosome, 40, 300, 546, 551, 580, 597, 640, 641, 659 Chronic Disease, 55, 368, 539, 546, 549 Chronic Fatigue Syndrome, 238, 278, 546 Chronic Obstructive Pulmonary Disease, 112, 137, 188, 189, 220, 251, 278, 299, 546 Chronic renal, 546, 602, 626 Chronotherapy, 174, 546 Chylomicrons, 547, 598 Ciliary, 547, 607, 643, 660 Ciliary Body, 547, 643, 660 Ciprofloxacin, 472, 547 Circadian, 96, 100, 119, 470, 546, 547 Circadian Rhythm, 96, 100, 470, 546, 547 Circulatory system, 547, 565, 618 Circumcision, 10, 547 CIS, 77, 89, 92, 128, 427, 547, 638 Cisplatin, 111, 547 Clamp, 15, 22, 44, 59, 109, 547 Clan, 79, 547 Clear cell carcinoma, 547, 558, 559 Clenbuterol, 178, 547 Clinical Medicine, 196, 547, 628 Clinical study, 34, 115, 547, 552 Clobetasol, 6, 402, 548 Clomiphene, 548 Clone, 58, 89, 92, 117, 548 Clonic, 548, 552 Cloning, 45, 61, 126, 265, 274, 448, 536, 548 Coagulation, 163, 422, 536, 548, 581, 625, 654 Coal, 444, 534, 548 Coca, 548 Cocaine, 33, 44, 46, 103, 449, 452, 548 Cochlea, 548, 589 Cochlear, 106, 445, 548, 649, 655, 662 Cochlear Diseases, 548, 655
Index 673
Cochlear Duct, 548, 649 Coenzyme, 303, 548, 573 Cofactor, 548, 611, 632, 654 Cognition, 4, 25, 37, 46, 56, 68, 72, 104, 115, 125, 202, 216, 308, 548 Coitus, 549, 552 Colitis, 7, 139, 231, 284, 445, 469, 549, 593 Collagen, 29, 133, 147, 249, 520, 533, 549, 570, 572, 575, 584, 591, 601, 626, 630 Collagen disease, 549, 584 Collagenous Colitis, 193, 549 Collapse, 368, 525, 538, 549, 644, 647 Colloidal, 522, 549, 563, 643 Colorectal, 95, 170, 193, 278, 408, 549 Colorectal Cancer, 278, 408, 549 Combination chemotherapy, 304, 549 Combination Therapy, 43, 419, 549, 568 Common Variable Immunodeficiency, 177, 549 Communicable disease, 549, 659 Complement, 55, 61, 102, 525, 549, 550, 576, 590, 625, 642 Complementary and alternative medicine, 271, 272, 296, 550 Complementary medicine, 272, 550 Complete remission, 312, 550, 636 Complete response, 7, 550 Computational Biology, 493, 496, 550 Computed tomography, 55, 537, 550, 640 Computer Simulation, 550 Computerized axial tomography, 550, 640 Computerized tomography, 313, 550 Conception, 550, 552, 572, 576, 648 Concomitant, 7, 8, 10, 15, 101, 134, 550, 641 Conduction, 22, 550, 610 Confounding, 259, 550 Confusion, 550, 659 Congestion, 283, 550, 567 Congestive heart failure, 541, 551 Conjugation, 31, 111, 116, 348, 536, 551, 650 Conjunctiva, 551, 594, 602, 633, 656, 658 Consciousness, 525, 551, 557, 561, 581, 638, 656 Consensus Sequence, 114, 433, 524, 551 Conserved Sequence, 414, 524, 551 Consolidation, 100, 104, 551 Constipation, 551, 593 Constitutional, 551, 608 Constriction, 54, 88, 119, 368, 551, 593, 640, 661, 663
Constriction, Pathologic, 551, 661 Consumption, 62, 68, 348, 551, 575, 617 Contact dermatitis, 150, 259, 551 Contamination, 229, 345, 551, 582 Contraception, 140, 150, 200, 354, 357, 434, 440, 451, 453, 454, 551, 596 Contraceptive Agents, 328, 406, 552, 558 Contractility, 86, 210, 526, 552, 563 Contraindications, ii, 552 Contralateral, 26, 552, 614, 636 Contrast Sensitivity, 552, 615 Control group, 14, 552 Controlled clinical trial, 5, 43, 552, 635 Controlled study, 33, 115, 210, 475, 552 Contusion, 113, 552 Convulsants, 82, 552 Convulsions, 528, 533, 552, 562, 611, 628 Coordination, 15, 22, 544, 552, 607 Copulation, 54, 552 Cor, 27, 30, 232, 308, 552, 553, 630 Cornea, 45, 149, 178, 186, 544, 552, 553, 594, 640, 649, 656, 665 Corneal Neovascularization, 184, 365, 553 Corneal Stroma, 530, 553 Corneal Transplantation, 553 Corneal Ulcer, 178, 553 Corneum, 553, 567 Coronary, 83, 311, 494, 541, 553, 604, 608 Coronary heart disease, 311, 541, 553 Coronary Thrombosis, 553, 604, 608 Corpus, 365, 553, 599, 609, 620, 624, 629, 642, 653 Corpus Luteum, 365, 553, 599, 629 Cortex, 69, 117, 524, 531, 544, 553, 566, 569, 572, 605, 633, 636 Cortical, 11, 35, 39, 68, 109, 125, 202, 275, 524, 553, 569, 610, 633, 641, 653 Corticotropin-Releasing Hormone, 30, 232, 308, 553 Cortisol, 4, 7, 26, 35, 87, 89, 99, 183, 228, 229, 339, 340, 342, 343, 364, 375, 402, 427, 522, 553, 664 Cortisone, 325, 359, 369, 377, 388, 505, 553, 558, 628 Cost Savings, 494, 554 C-Peptide, 311, 554 Cranial, 532, 544, 554, 569, 580, 591, 610, 615, 619, 621, 646, 658, 660, 662 Craniocerebral Trauma, 533, 554, 580, 584, 653, 655 Creatine, 133, 268, 309, 554 Creatine Kinase, 133, 554
674 Steroids
Creatinine, 554, 594 Cribriform, 554, 613 Critical Illness, 134, 554 Cross Reactions, 150, 554 Crossing-over, 554, 636 Croton Oil, 263, 554, 623 Croup, 214, 238, 554 Cryptosporidiosis, 532, 554 Crystallization, 403, 554 Cues, 26, 554 Culture Media, 356, 411, 431, 522, 554 Curare, 555, 618 Curative, 446, 555, 611, 639, 653 Curcumin, 28, 555 Curettage, 144, 555 Curette, 555 Cutaneous, 78, 134, 148, 260, 278, 305, 361, 536, 540, 551, 555, 585, 599, 624 Cyanides, 555, 612 Cyclin, 52, 555 Cyclooxygenase Inhibitors, 374, 375, 555 Cyclophosphamide, 43, 48, 147, 233, 240, 253, 310, 312, 555 Cyproterone, 555, 573 Cysteine, 288, 292, 542, 555, 565, 650 Cysteine Endopeptidases, 542, 555, 565 Cystitis, 239, 445, 555 Cytochrome b, 63, 88, 556 Cytochrome b5, 63, 88, 556 Cytogenetics, 556, 640 Cytomegalovirus, 556, 574 Cytomegalovirus Infections, 556, 574 Cytoplasm, 439, 529, 533, 540, 543, 556, 563, 566, 579, 639, 651 Cytoskeleton, 98, 556, 590 Cytotoxic, 43, 60, 69, 153, 194, 246, 412, 417, 556, 587, 634, 635, 644, 658 Cytotoxicity, 199, 275, 523, 547, 556, 594 D Daclizumab, 130, 138, 153, 311, 314, 556 Danazol, 148, 556 Data Collection, 16, 556 Databases, Bibliographic, 493, 556 Day Care, 444, 557 De novo, 235, 557 Decarboxylation, 535, 557, 583 Decidua, 557, 605, 625, 657 Defense Mechanisms, 557, 590 Degenerative, 115, 557, 582, 600, 616, 638 Dehydration, 335, 336, 344, 557 Deletion, 40, 49, 529, 557 Dementia, 28, 557, 559
Denaturation, 557, 627 Dendrites, 100, 557, 579, 610, 613, 633 Dendritic, 22, 100, 557, 602, 638 Density, 17, 21, 45, 56, 71, 87, 97, 126, 142, 153, 161, 164, 213, 216, 221, 223, 262, 264, 310, 316, 537, 544, 557, 598, 606, 614, 646 Dental Care, 241, 557 Dental Caries, 557, 573 Dental Cements, 523, 557 Dental Materials, 447, 557 Dentate Gyrus, 38, 557, 583 Dentists, 446, 558 Deoxycholic Acid, 400, 558 Deoxyribonucleic, 558, 639 Deoxyribonucleic acid, 558, 639 Depersonalization, 558, 619, 640 Depolarization, 558, 644 Depressive Disorder, 25, 99, 558, 598 Deprivation, 88, 148, 223, 405, 524, 558 Derealization, 558, 619 Dermal, 558, 597 Dermatitis, 83, 146, 158, 247, 252, 259, 278, 283, 558, 562 Dermatologic Agents, 558 Dermatology, 77, 129, 146, 147, 150, 158, 167, 170, 181, 212, 231, 252, 253, 256, 259, 476, 558 Dermatosis, 129, 558 DES, 262, 525, 558, 559 Desiccation, 45, 558 Desogestrel, 403, 558 Detoxification, 558, 577 Deuterium, 110, 558, 584 Dextroamphetamine, 525, 558 Diabetes Insipidus, 509, 559 Diabetes Mellitus, 8, 9, 273, 278, 311, 313, 314, 559, 577, 581 Diabetic Retinopathy, 167, 365, 559, 624 Diagnostic procedure, 321, 445, 481, 559 Dialyzer, 559, 581 Diaphragm, 112, 354, 559, 582 Diarrhea, 8, 305, 524, 554, 559, 593 Diastolic, 559, 585 Diclofenac, 288, 466, 559 Diclofenac Sodium, 559 Diencephalon, 559, 585, 620, 630, 652, 653 Diethylstilbestrol, 322, 327, 363, 558, 559 Diffuse Axonal Injury, 538, 559 Diffusion, 535, 559, 560, 580, 589, 592 Digestion, 57, 523, 534, 537, 559, 562, 588, 591, 598, 621, 648
Index 675
Digestive system, 318, 559, 607 Digestive tract, 560, 644 Digitalis, 541, 560, 616, 649 Digoxigenin, 58, 560 Dihydroxy, 325, 332, 344, 376, 381, 382, 397, 398, 416, 522, 560, 573 Dilatation, 526, 538, 560, 629, 661 Dilatation, Pathologic, 560, 661 Dilation, 119, 191, 537, 560, 584, 661 Dilator, 119, 560 Dilution, 251, 560, 625 Dimerization, 89, 439, 560 Dimethyl, 329, 337, 354, 403, 446, 560 Diosgenin, 326, 335, 336, 385, 560 Diploid, 560, 625 Discrimination, 18, 33, 532, 560 Disease Progression, 258, 560, 662 Disease Vectors, 560, 589 Disinfectant, 545, 560, 569, 621 Disintegrins, 118, 560 Disposition, 116, 164, 560 Dissociation, 521, 560, 592 Distal, 4, 49, 140, 350, 469, 532, 561, 563, 632, 633 Distention, 95, 561 Diuresis, 539, 561, 653 Diuretic, 387, 561, 593, 601, 645 Dizziness, 561, 618, 662 Domesticated, 18, 561 Dopamine, 21, 44, 46, 65, 91, 103, 300, 525, 539, 548, 559, 561, 596, 606, 623 Doping, 148, 170, 171, 174, 561 Dorsal, 68, 76, 561, 567, 627, 646, 647 Dorsum, 561, 575 Dose-dependent, 159, 561 Double-blinded, 33, 561 Drinking Behavior, 561, 650 Drive, ii, vi, 5, 8, 84, 90, 107, 261, 426, 443, 444, 505, 561, 592, 596 Drug Delivery Systems, 440, 561 Drug Interactions, 33, 487, 561 Drug Tolerance, 561, 655 Dry Eye Syndrome, 45, 347, 562 Duct, 77, 116, 525, 542, 545, 562, 565, 570, 618, 639, 651, 660 Duke, 44, 113, 266, 364, 562 Duodenum, 534, 562, 565, 575, 648 Dura mater, 562, 602, 618 Dydrogesterone, 360, 562 Dyes, 525, 534, 562, 650 Dynorphins, 562, 614 Dysmenorrhea, 118, 419, 562
Dyspareunia, 562, 568 Dyspepsia, 562, 588 Dysphoric, 56, 68, 558, 562 Dysplasia, 70, 235, 498, 562 Dyspnea, 55, 368, 562, 618, 647 Dyspnoea, 158, 562 Dystrophy, 303, 306, 309, 396, 497, 562 Dysuria, 9, 562 E Eating Disorders, 208, 562 Eclampsia, 562, 628 Ectopic, 106, 118, 562 Eczema, 83, 279, 562 Edema, 53, 71, 551, 559, 562, 591, 609, 628 Effector, 65, 68, 119, 332, 362, 519, 549, 562, 594, 611, 623 Effector cell, 562, 594, 611 Egg Yolk, 379, 563 Eicosanoids, 61, 427, 555, 563 Ejaculation, 563, 642 Ejection fraction, 34, 563 Elasticity, 530, 563 Elastin, 71, 549, 563, 570, 658 Elective, 48, 187, 545, 563 Electroacupuncture, 273, 563 Electrocardiogram, 305, 311, 313, 563 Electrocoagulation, 548, 563 Electrode, 109, 563 Electrolysis, 348, 527, 542, 563 Electrolyte, 347, 522, 553, 563, 573, 594, 605, 613, 628, 645 Electrons, 528, 533, 563, 592, 600, 605, 617, 634 Electrophoresis, 81, 563 Electrophysiological, 37, 39, 75, 84, 110, 237, 563 Electroplating, 542, 563, 650 Elementary Particles, 563, 600, 611, 632 Embolism, 368, 563 Embolus, 563, 588 Embryo Transfer, 85, 564 Embryogenesis, 564, 643 Embryology, 564, 611 Emetic, 554, 564 Emollient, 564, 578, 613 Emphysema, 279, 546, 564 Empirical, 64, 96, 564 Emulsion, 532, 564, 573 Enanthate, 334, 418, 564 Encapsulated, 564 Encephalitis, 199, 564 Encephalitis, Viral, 564
676 Steroids
Encephalomyelitis, 184, 564 Endocarditis, 540, 564 Endocrine Glands, 564, 565, 619 Endocrine System, 67, 325, 425, 565, 610 Endocytosis, 543, 565 Endolymphatic Duct, 565 Endolymphatic Sac, 164, 565 Endometriosis, 118, 258, 279, 556, 565, 596, 612 Endopeptidases, 555, 565, 631 Endophthalmitis, 258, 565 Endorphins, 565, 614, 630 Endoscope, 565 Endoscopic, 191, 470, 530, 565 Endostatin, 78, 565 Endothelial cell, 28, 51, 71, 78, 88, 166, 202, 218, 232, 343, 536, 565, 572, 654 Endothelium, 88, 172, 565, 566, 612, 625 Endothelium, Lymphatic, 565 Endothelium, Vascular, 565 Endothelium-derived, 566, 612 Endotoxic, 566, 597 Endotoxin, 30, 566, 658 End-stage renal, 48, 546, 566, 602, 626 Enema, 4, 566 Energy balance, 566, 596, 624 Enhancer, 391, 566, 638 Enkephalin, 72, 534, 566, 630 Enteral Nutrition, 470, 566 Enteritis, 111, 566 Enterocolitis, 566 Entorhinal Cortex, 29, 566, 583 Enucleation, 253, 566 Environmental Exposure, 566, 614 Environmental Health, 76, 492, 494, 566 Enzyme Inhibitors, 454, 566, 625 Eosinophil, 76, 238, 566 Eosinophilia, 566, 571 Eosinophilic, 167, 566, 571 Ephedrine, 178, 566 Epicondylitis, 478, 567 Epidemiological, 55, 95, 299, 422, 439, 567 Epidermal, 50, 159, 186, 232, 567, 594, 597, 602, 657 Epidermal Growth Factor, 50, 159, 232, 567, 657 Epidermis, 413, 519, 536, 553, 567, 583, 593, 594, 597, 620, 629, 633, 647 Epidural, 130, 134, 166, 168, 173, 179, 197, 206, 256, 567, 646 Epigastric, 567, 618
Epinephrine, 521, 535, 547, 561, 567, 612, 659 Epithelial Cells, 58, 224, 273, 407, 433, 567, 582, 594, 595, 605 Epithelium, 45, 58, 86, 426, 533, 565, 567, 575, 593, 642, 657, 665 Equalization, 347, 567 Equilenin, 397, 567 Equilin, 39, 127, 567 Erectile, 441, 567, 620 Erection, 567 Erythema, 227, 279, 361, 551, 567, 650 Erythema Multiforme, 361, 567 Erythema Nodosum, 227, 567 Erythrocyte Indices, 536, 568 Erythrocytes, 140, 230, 265, 526, 536, 537, 568, 636, 642 Erythromelalgia, 129, 568 Erythromycin, 433, 532, 568 Esophageal, 168, 191, 252, 568 Esophageal Stricture, 191, 568 Esophagus, 235, 559, 560, 568, 580, 601, 623, 636, 648 Esotropia, 568, 648 Essential Tremor, 498, 568 Esterification, 141, 382, 568 Estramustine, 64, 568 Estrogen Replacement Therapy, 39, 98, 568 Estrone, 97, 322, 327, 330, 363, 378, 397, 419, 429, 436, 439, 440, 568 Ethanol, 33, 40, 61, 62, 241, 300, 402, 522, 569, 571 Ether, 322, 349, 358, 360, 397, 419, 439, 569 Ethmoid, 569, 613, 619 Etomidate, 57, 569 Etoposide, 65, 569 Etretinate, 444, 569 Eukaryotic Cells, 569, 588, 615 Eustachian tube, 533, 569 Evoke, 569, 648 Evoked Potentials, 142, 569 Excipient, 333, 434, 569 Excitability, 22, 25, 75, 569, 608 Excitation, 109, 112, 569 Excitatory, 22, 26, 75, 82, 120, 524, 569, 578, 611, 635 Excitatory Amino Acids, 569, 611 Excrete, 529, 569, 594 Exercise Test, 311, 570 Exercise Tolerance, 24, 570 Exhaustion, 527, 570, 647
Index 677
Exocrine, 570, 618 Exocytosis, 570, 583, 651 Exotoxin, 570, 647 Exotropia, 570, 648 Expectorant, 570, 645 Expiration, 570, 637 Expiratory, 71, 570 Expressed Sequence Tags, 570 Extensor, 570, 632, 663 External-beam radiation, 570, 593, 634, 664 Extracellular Matrix, 108, 570, 572, 590, 601, 616 Extracellular Matrix Proteins, 570, 601 Extracellular Space, 570, 571, 604 Extracorporeal, 305, 571, 624 Extraction, 7, 156, 180, 241, 355, 571 Extrapyramidal, 561, 571 Extravasation, 95, 571, 581 F Facial, 144, 506, 571, 601, 620, 662 Fallopian Tubes, 571, 637 Family Planning, 493, 571 Family Relations, 163, 571 Fasciitis, 167, 571 Fat, 16, 113, 171, 175, 233, 235, 310, 368, 519, 520, 530, 534, 537, 539, 541, 544, 546, 552, 553, 563, 571, 594, 596, 597, 607, 639, 641, 645, 650, 654 Fatigue, 3, 21, 112, 158, 546, 571, 580, 607 Febrile, 571 Feeding Behavior, 571 Femoral, 541, 571, 582 Femoral Artery, 541, 571 Femoral Neck Fractures, 571, 582 Femur, 571, 582 Fermentation, 366, 378, 379, 383, 384, 386, 522, 571 Fertility Agents, 324, 571 Fertilizers, 571, 650 Fetal Blood, 546, 572 Fetal Growth Retardation, 572 Fetus, 53, 62, 79, 90, 116, 299, 306, 410, 546, 572, 573, 624, 629, 659, 660 Fibrin, 536, 572, 625, 654, 655 Fibrinogen, 572, 625, 654 Fibroblast Growth Factor, 217, 572 Fibroblasts, 114, 217, 571, 572, 590 Fibroid, 572, 595 Fibronectin, 572 Fibrosarcoma, 571, 572
Fibrosis, 159, 215, 225, 236, 239, 310, 368, 498, 523, 572, 640 Fibula, 527, 572, 627 Filtration, 71, 380, 572, 579, 594 Finasteride, 407, 430, 572 Fissure, 557, 572 Fistula, 572, 575, 652 Fixation, 572, 642 Flatus, 573, 575 Flexor, 570, 573, 597, 645 Fluid Therapy, 573, 613 Flumazenil, 33, 573 Fluocinonide, 6, 379, 548, 573 Fluocortolone, 379, 573 Fluorescence, 58, 61, 109, 417, 420, 573 Fluorescence Polarization, 420, 573 Fluorine, 331, 379, 573 Fluorouracil, 573, 596 Fluoxetine, 69, 124, 573 Fluoxymesterone, 200, 573 Fluprednisolone, 379, 573 Flushing, 345, 573 Flutamide, 42, 45, 573 Foetoplacental, 573, 613 Fold, 51, 109, 356, 380, 437, 438, 572, 573, 603, 629 Follicles, 50, 573, 574, 589 Follicular Fluid, 200, 220, 574 Follicular Phase, 574 Folliculitis, 527, 574 Foramen, 574, 601, 622, 650 Forearm, 536, 571, 574, 601 Fossa, 544, 574 Fourth Ventricle, 546, 574, 653 Frail Elderly, 16, 574 Frontal Lobe, 25, 574 Fructose, 574, 578, 592 Fungi, 379, 401, 456, 528, 531, 551, 565, 574, 591, 604, 664 Fungicides, Industrial, 528, 574 Fungistatic, 534, 574 Fungus, 383, 540, 544, 574 G Gait, 16, 574 Gallbladder, 519, 534, 535, 559, 574 Gallstones, 534, 545, 574 Gamma Rays, 574, 607, 634 Ganciclovir, 312, 574 Ganglia, 65, 519, 533, 574, 610, 621, 647, 651 Ganglion, 575, 615, 638, 662, 665 Gap Junctions, 575, 651
678 Steroids
Gas exchange, 34, 71, 575, 583, 637, 661 Gasoline, 534, 575 Gastric, 365, 567, 575, 580, 583, 584, 621 Gastric Juices, 575, 621 Gastric Mucosa, 575, 621 Gastrin, 575, 583 Gastroduodenal, 8, 575 Gastroenteritis, 538, 575 Gastrointestinal tract, 569, 572, 575, 595, 596, 620, 643, 648, 658 Gastrostomy, 566, 575 Gelatin, 555, 575, 578, 654 Gels, 361, 575 Genetic Code, 576, 612 Genetic Engineering, 536, 548, 576 Genetic Markers, 88, 576 Genetic Techniques, 576 Genetic testing, 576, 627 Genetics, 21, 52, 60, 92, 220, 453, 520, 551, 556, 576, 622, 643 Genital, 547, 576, 592, 660 Genitourinary, 576, 660 Genomics, 410, 576 Genotype, 42, 576, 623 Germ Cells, 48, 432, 576, 602, 614, 617, 645, 646, 653 Gestation, 72, 77, 90, 137, 154, 317, 358, 576, 621, 625, 628 Gestation period, 358, 576 Gestational, 572, 576 Gestrinone, 148, 576 Giant Cells, 576, 640 Giardiasis, 576, 604 Ginseng, 290, 293, 576 Glioblastoma, 46, 576 Glomerular, 5, 43, 48, 577, 592, 594, 601, 636 Glomerular Filtration Rate, 43, 577, 594, 601 Glomeruli, 60, 577, 602, 613 Glomerulonephritis, 60, 191, 211, 309, 312, 577, 586 Glomerulosclerosis, 5, 43, 136, 173, 253, 307, 309, 310, 577 Glomerulus, 577, 609 Glottis, 577, 582, 622 Glucose Intolerance, 559, 577 Glucose tolerance, 8, 482, 577 Glucose Tolerance Test, 577 Glucuronic Acid, 577, 581, 660 Glucuronides, 195, 298, 577
Glutamate, 22, 37, 54, 68, 82, 109, 120, 300, 524, 578, 593, 603, 623, 635 Glutamic Acid, 524, 578, 630 Glutamine, 309, 431, 578 Glutathione Peroxidase, 578, 642 Glycerol, 41, 79, 539, 578, 623 Glycerophospholipids, 578, 623 Glycine, 126, 534, 545, 546, 558, 560, 578, 598, 643, 649 Glycocholic Acid, 373, 385, 578 Glycogen, 111, 578, 607 Glycols, 578, 584 Glycoprotein, 77, 93, 116, 145, 203, 274, 410, 572, 576, 578, 595, 643, 654, 658 Glycoside, 263, 578, 616 Gonad, 77, 87, 89, 578 Gonadorelin, 578, 596 Gonadotropic, 90, 578 Gonadotropin, 44, 50, 84, 91, 154, 156, 177, 208, 210, 217, 220, 465, 578, 596 Goniotomy, 578, 656 Governing Board, 579, 628 Grade, 304, 579 Grading, 235, 579 Graft, 83, 177, 235, 240, 246, 304, 308, 309, 315, 317, 365, 529, 579, 583, 587, 608, 632 Graft Rejection, 308, 365, 579, 587 Graft Survival, 83, 579 Grafting, 579, 588 Graft-versus-host disease, 235, 309, 529, 579, 608, 632 Gram-negative, 233, 433, 538, 566, 579, 638 Gram-Negative Bacteria, 233, 566, 579, 638 Granule, 15, 38, 431, 557, 579, 626, 639 Granulocytes, 187, 579, 596, 608, 644, 664 Granuloma, 253, 579 Granulosa Cells, 77, 217, 298, 346, 579, 589, 599 Grasshoppers, 273, 579 Gravis, 127, 242, 579 Growth, 16, 19, 26, 29, 39, 50, 51, 74, 77, 86, 88, 92, 93, 98, 101, 118, 121, 124, 134, 138, 141, 147, 152, 159, 162, 166, 173, 177, 178, 183, 184, 186, 205, 217, 222, 224, 231, 232, 238, 247, 248, 300, 308, 325, 332, 341, 355, 362, 364, 400, 401, 405, 408, 411, 412, 414, 419, 422, 425, 426, 427, 431, 440, 441, 453, 457, 459, 470, 497, 505, 506, 520, 522, 525, 526, 527, 528, 529, 533, 534, 536, 543, 554, 565, 567, 571, 572, 574, 579, 580, 582, 585, 590, 594, 595, 600, 609, 610, 613,
Index 679
614, 615, 625, 627, 641, 651, 654, 655, 657, 658, 659, 661, 662 Growth Cones, 98, 579 Growth factors, 19, 29, 50, 51, 118, 159, 411, 431, 579 Growth Inhibitors, 412, 580 Guanylate Cyclase, 71, 580, 612 H Habitual, 545, 580 Haemodialysis, 225, 580 Hair follicles, 574, 580, 663 Half-Life, 31, 580 Hantavirus, 23, 580 Haploid, 432, 580, 625 Haptens, 521, 580, 634 Headache, 168, 278, 284, 539, 580, 584, 629 Health Behavior, 248, 580 Health Services, 56, 580 Health Status, 6, 312, 580 Heart attack, 213, 541, 580 Heart failure, 34, 526, 566, 580 Heartburn, 580, 588 Hematocrit, 355, 536, 568, 580 Hematoma, 194, 581 Hematopoietic Stem Cell Transplantation, 246, 581 Hematopoietic Stem Cells, 581 Hematuria, 10, 581, 602 Heme, 535, 555, 556, 581, 608 Hemiparesis, 538, 581 Hemodialysis, 15, 559, 581, 594 Hemodynamics, 48, 119, 581 Hemoglobin, 526, 534, 536, 568, 581, 596, 653 Hemoglobinuria, 497, 581 Hemolytic, 571, 581, 653 Hemorrhage, 53, 194, 339, 340, 343, 364, 376, 554, 563, 580, 581, 633, 649, 652, 663 Hemostasis, 422, 581, 590, 643 Heparin, 149, 163, 231, 339, 340, 343, 364, 365, 375, 581 Hepatic, 5, 122, 178, 194, 204, 226, 522, 577, 581, 598, 606, 622 Hepatic Encephalopathy, 5, 581 Hepatitis, 4, 147, 161, 168, 178, 191, 195, 240, 244, 247, 274, 280, 494, 504, 505, 582 Hepatitis A, 494, 582 Hepatitis C, 178, 244, 582 Hepatocyte, 51, 545, 582 Hepatocyte Growth Factor, 51, 582 Hepatoma, 116, 582 Hepatomegaly, 229, 582
Hepatotoxicity, 255, 582 Hepatovirus, 582 Hereditary, 582, 610, 625, 638, 653 Heredity, 519, 575, 576, 582 Herpes, 46, 179, 447, 520, 582 Herpes Zoster, 582 Heterodimer, 64, 582 Heterogeneity, 82, 202, 521, 582 Heterotrophic, 574, 582 Heterotropia, 582, 648 Hibernation, 13, 582 Hiccup, 249, 582 Hip Fractures, 571, 582 Hippocampus, 18, 22, 25, 38, 72, 98, 100, 114, 126, 176, 557, 582, 597, 633, 650 Hirsutism, 175, 180, 241, 323, 327, 332, 355, 362, 363, 407, 555, 583, 585 Histamine, 238, 334, 525, 535, 547, 583, 618 Histamine Release, 525, 583, 618 Histidine, 583 Histology, 8, 45, 53, 583, 619 Hoarseness, 259, 554, 583 Homeostasis, 67, 165, 176, 417, 420, 583 Homogeneous, 20, 530, 583 Homologous, 36, 99, 433, 523, 554, 583, 641, 642, 651, 653 Homosteroids, 347, 583 Hormonal therapy, 74, 227, 264, 583 Hormone Replacement Therapy, 76, 96, 120, 140, 186, 440, 583 Hormone therapy, 91, 97, 530, 583 Horny layer, 567, 583 Humoral, 21, 579, 583 Humour, 251, 583 Hyaline membrane disease, 368, 583 Hybrid, 12, 60, 183, 406, 548, 584, 614 Hybridization, 51, 97, 584, 614 Hybridomas, 584, 590 Hydrocephalus, 584, 591, 593 Hydrochloric Acid, 381, 428, 584 Hydrocortisone, 359, 377, 380, 388, 389, 469, 486, 584 Hydrogen Cyanide, 555, 584, 612 Hydrogen Peroxide, 349, 382, 578, 584, 597 Hydrophobic, 427, 578, 584, 597 Hydroxides, 584 Hydroxyl Radical, 91, 584 Hydroxylation, 63, 142, 322, 327, 330, 343, 359, 363, 366, 383, 584, 658 Hydroxylysine, 549, 584 Hydroxyproline, 549, 584
680 Steroids
Hydroxysteroids, 383, 585 Hyperaldosteronism, 183, 585 Hyperalgesia, 95, 585 Hyperandrogenism, 90, 585 Hyperbilirubinemia, 585, 593 Hypercalcemia, 405, 585 Hypercholesterolemia, 61, 280, 316, 585 Hyperglycemia, 8, 585 Hyperplasia, 90, 109, 127, 128, 178, 235, 237, 355, 408, 497, 509, 585, 597 Hypersecretion, 90, 100, 585, 641 Hypersensitivity, 277, 523, 525, 566, 585, 596, 639, 642 Hypertrichosis, 583, 585 Hypertrophy, 198, 332, 362, 408, 534, 552, 585, 658 Hyperuricemia, 585, 658 Hypesthesia, 585, 610 Hypnotic, 32, 100, 110, 533, 569, 585, 628 Hypogammaglobulinemia, 549, 585 Hypogonadism, 32, 59, 112, 249, 428, 573, 585 Hypopharynx, 131, 585 Hypophysis, 585, 642 Hypotension, 552, 585 Hypothyroidism, 162, 509, 586 Hypovolemia, 68, 586 Hypoxemia, 586 Hypoxia, 55, 368, 586 I Iatrogenic, 222, 368, 586 Ibuprofen, 31, 194, 291, 484, 486, 586 Id, 266, 275, 372, 393, 394, 395, 502, 504, 507, 508, 514, 516, 586 Idiopathic, 5, 10, 59, 111, 224, 361, 586, 640 Ileal, 61, 472, 586 Ileum, 586 Imaging procedures, 586, 656 Imidazole, 536, 569, 583, 586, 604 Immune Complex Diseases, 528, 586, 625 Immune function, 60, 312, 429, 586, 587, 657 Immune Sera, 586 Immunity, 176, 413, 586, 587, 657 Immunization, 475, 481, 521, 586, 587, 629, 642 Immunoassay, 345, 346, 461, 554, 587 Immunoblotting, 11, 587 Immunocompromised, 587 Immunodeficiency, 145, 237, 473, 474, 475, 497, 504, 505, 549, 585, 587
Immunodeficiency syndrome, 473, 474, 475, 549, 587 Immunofluorescence, 150, 587 Immunogenic, 412, 587, 597, 634 Immunoglobulin, 177, 185, 411, 412, 527, 587, 606 Immunohistochemistry, 48, 53, 91, 587 Immunologic, 108, 111, 391, 453, 521, 545, 586, 587, 635, 654 Immunophilin, 539, 587 Immunosuppressant, 523, 573, 587 Immunosuppressive Agents, 5, 6, 60, 83, 111, 160, 236, 252, 587 Immunosuppressive therapy, 111, 205, 587 Immunotherapy, 475, 521, 535, 587 Immunotoxins, 412, 587, 634 Impairment, 25, 45, 100, 115, 152, 531, 545, 587, 591, 603 Implant radiation, 587, 591, 593, 634, 664 Impotence, 408, 567, 588, 646 In situ, 11, 30, 38, 45, 46, 51, 70, 91, 93, 97, 103, 414, 436, 440, 588 In Situ Hybridization, 11, 38, 45, 70, 91, 103, 588 Incision, 144, 578, 588, 592, 595 Incontinence, 233, 255, 566, 584, 588, 646, 649 Incubated, 436, 437, 588 Incubation, 36, 379, 588, 622 Incubation period, 588, 622 Indicative, 100, 422, 427, 447, 588, 620, 660 Indigestion, 6, 588 Indomethacin, 31, 291, 588 Induction therapy, 172, 228, 588 Infancy, 588, 639 Infant Mortality, 316, 588 Infantile, 198, 263, 588 Infarction, 91, 537, 584, 588, 626, 637 Infertility, 84, 118, 129, 307, 453, 505, 571, 589 Infiltration, 577, 589, 665 Inflammatory bowel disease, 4, 7, 111, 182, 209, 305, 421, 445, 469, 470, 471, 589 Informed Consent, 314, 589 Infusion, 28, 32, 41, 246, 313, 314, 589, 604, 657 Ingestion, 577, 589, 604, 626, 653 Inhalation, 34, 55, 164, 192, 368, 463, 484, 485, 486, 521, 582, 589, 626, 644 Inhibin, 59, 157, 220, 589 Initiation, 42, 197, 232, 589, 630, 649, 656
Index 681
Initiator, 324, 325, 589 Inlay, 589, 638 Inner ear, 106, 548, 589, 595, 619 Innervation, 14, 26, 45, 589, 601 Inoperable, 251, 589 Inorganic, 537, 547, 555, 584, 589, 607, 612, 623, 655 Inotropic, 82, 561, 589 Inpatients, 85, 589 Insecticides, 401, 589, 622, 664 Insight, 12, 14, 24, 36, 38, 45, 48, 55, 60, 62, 63, 71, 93, 103, 111, 201, 589 Insomnia, 96, 100, 589, 629 Instar, 273, 590 Instillation, 446, 590 Insulator, 590, 607 Insulin-dependent diabetes mellitus, 219, 590 Insulin-like, 173, 178, 183, 217, 222, 590 Integrins, 590 Intensive Care, 129, 139, 192, 590 Interferon, 78, 147, 191, 195, 590, 600 Interferon-alpha, 195, 590 Interleukin-1, 27, 176, 224, 250, 590 Interleukin-2, 190, 195, 590 Interleukin-6, 28, 29, 224, 225, 590 Interleukins, 587, 590 Intermittent, 115, 307, 415, 562, 573, 591 Internal Medicine, 7, 29, 71, 210, 251, 255, 257, 565, 591 Internal radiation, 591, 593, 634, 664 Interneurons, 44, 591 Interpersonal Relations, 115, 591 Interstitial, 79, 218, 225, 445, 537, 553, 571, 591, 593, 609, 636, 664 Interstitial Collagenase, 218, 591 Intervention Studies, 17, 591 Intervertebral, 591, 599, 634, 640 Intervertebral Disk Displacement, 591, 599, 634, 640 Intestinal, 61, 111, 251, 301, 312, 398, 472, 541, 545, 554, 558, 566, 577, 591, 594, 600, 663 Intestinal Flora, 111, 591 Intestinal Obstruction, 251, 591 Intestine, 469, 534, 537, 549, 566, 591, 595 Intoxication, 591, 664 Intracellular Membranes, 591, 602 Intracranial Hypertension, 580, 584, 591, 655 Intramuscular, 130, 352, 408, 504, 591, 619, 657
Intramuscular injection, 408, 591 Intraocular, 192, 310, 339, 342, 374, 375, 565, 591, 613 Intraocular pressure, 192, 339, 342, 374, 375, 591, 613 Intrathecal, 27, 54, 73, 591 Intravenous, 7, 33, 48, 130, 157, 178, 184, 192, 201, 214, 391, 589, 591, 604, 619 Intravesical, 446, 592 Intrinsic, 73, 521, 533, 592 Intubation, 198, 259, 542, 592 Inulin, 577, 592 Invasive, 6, 19, 68, 118, 171, 407, 586, 592, 600 Invertebrates, 560, 592 Involuntary, 533, 568, 592, 608, 636, 645, 646, 655 Involution, 339, 340, 343, 364, 376, 592 Iodine, 331, 386, 391, 397, 419, 592 Ion Channels, 22, 110, 417, 531, 592, 611, 635, 651 Ion Exchange, 544, 592, 593 Ion Transport, 592, 605 Ionization, 143, 155, 167, 592, 593 Ionizing, 523, 566, 592, 601, 634, 659 Ions, 398, 533, 540, 545, 560, 563, 584, 592, 606, 645 Iontophoresis, 478, 592 Ipsilateral, 26, 593, 636 Iris, 552, 579, 593, 633, 660 Irradiation, 163, 360, 391, 537, 593, 604, 664 Irritable Bowel Syndrome, 471, 593 Ischemia, 53, 91, 531, 538, 593, 611, 637 Islet, 311, 313, 314, 593 Isoenzyme, 554, 593 Isopropyl, 331, 345, 393, 402, 593 Isosorbide, 403, 593 Isozymes, 407, 593 Itraconazole, 121, 225, 593 J Jaundice, 158, 585, 593 Jejunostomy, 566, 593 K Kainate, 560, 593, 635 Kb, 492, 593, 594 Keratin, 593, 594, 641 Keratinocyte growth factor, 315, 594 Keratinocytes, 594 Keratitis, 553, 594 Keratoconjunctivitis, 347, 553, 594, 643 Keratoconjunctivitis Sicca, 347, 594, 643
682 Steroids
Ketone Bodies, 519, 594 Kidney Disease, 9, 15, 307, 309, 311, 312, 313, 314, 318, 445, 492, 498, 594 Kidney Failure, 566, 577, 594, 601 Kidney Failure, Acute, 594 Kidney Failure, Chronic, 594 Kidney Transplantation, 6, 152, 230, 256, 264, 594 Killer Cells, 594 Kilobase, 145, 594 Kinetic, 69, 274, 468, 592, 595 L Labile, 18, 31, 549, 595 Labyrinth, 548, 565, 589, 595, 642, 662 Labyrinthitis, 224, 595 Lacrimal, 45, 594, 595, 602, 633, 643 Lacrimal gland, 45, 595, 633 Lactation, 595, 613, 618, 630 Laminin, 169, 533, 570, 595 Lamivudine, 195, 595 Laparotomy, 595 Large Intestine, 549, 559, 560, 591, 595, 636, 644 Larva, 105, 595, 603 Laryngeal, 163, 595 Larynx, 577, 585, 595, 649, 656, 660 Laser therapy, 227, 595 Latency, 595 Latent, 595, 628 Lavage, 71, 595 Laxative, 522, 545, 595, 645 Lectin, 595, 602 Leflunomide, 444, 595 Leiomyoma, 74, 203, 572, 595, 645 Lens, 58, 542, 595 Leprosy, 148, 213, 596 Leptin, 79, 113, 146, 152, 175, 176, 195, 196, 206, 232, 596 Lesion, 5, 26, 98, 230, 255, 536, 579, 596, 598, 646, 659 Lethal, 60, 109, 116, 533, 596 Lethargy, 408, 584, 586, 596 Leucine, 41, 534, 596, 621 Leucocyte, 368, 566, 596, 600 Leukapheresis, 305, 596 Leukemia, 89, 275, 304, 309, 497, 556, 596, 620 Leukocytes, 31, 187, 305, 368, 533, 536, 537, 545, 579, 588, 590, 596, 658 Leukoencephalopathy, 171, 225, 596 Leukoplakia, 214, 596 Leukotrienes, 334, 480, 530, 563, 596
Leuprolide, 249, 596 Levamisole, 9, 596 Levodopa, 596, 641 Levonorgestrel, 403, 596, 612 Libido, 25, 66, 107, 408, 441, 526, 596 Library Services, 514, 596 Lichen Planus, 6, 361, 447, 569, 597 Lidocaine, 534, 597 Life cycle, 536, 574, 595, 597, 613, 633 Ligament, 597, 631, 647 Ligands, 12, 22, 27, 57, 61, 86, 97, 122, 143, 203, 262, 425, 427, 543, 590, 597 Ligation, 53, 597 Limbic, 65, 525, 597 Limbic System, 525, 597 Linear Models, 17, 597 Linkage, 31, 129, 544, 576, 597 Lipid A, 422, 597 Lipid Bilayers, 597 Lipid Peroxidation, 53, 396, 597, 617 Lipoid, 90, 109, 128, 307, 597 Lipolysis, 78, 597 Lipomatosis, 168, 199, 597 Lipophilic, 82, 427, 597 Lipopolysaccharide, 579, 597 Lipoprotein, 98, 126, 196, 316, 579, 597, 599 Liposomes, 230, 265, 598 Lipoxygenase, 11, 530, 596, 598 Lithium, 302, 376, 391, 430, 598 Lithocholic Acid, 400, 598 Liver Cirrhosis, 598 Liver Neoplasms, 598, 662 Liver scan, 598, 640 Liver Transplantation, 161, 172, 200, 228, 231, 235, 236, 240, 247, 598 Lobe, 598, 630, 663 Locomotion, 44, 598, 625 Locomotor, 65, 103, 300, 598 Longitudinal study, 102, 196, 216, 598 Long-Term Potentiation, 75, 598 Loop, 78, 599 Lordosis, 96, 599 Low Back Pain, 166, 281, 599 Low-density lipoprotein, 396, 598, 599 Lucida, 595, 599 Luciferase, 49, 77, 599 Lumbar, 73, 112, 129, 173, 196, 542, 591, 599, 647 Lumbar puncture, 129, 599, 647 Lumpectomy, 407, 599 Lung Transplantation, 152, 599
Index 683
Lupus, 50, 240, 281, 283, 369, 421, 452, 502, 505, 599, 652 Luteal Phase, 51, 168, 232, 265, 599, 605 Lutein Cells, 599, 630 Lycopene, 599 Lymph, 71, 139, 532, 544, 547, 565, 583, 599, 600, 601, 612, 633, 634, 640, 650 Lymph node, 139, 532, 544, 599, 600, 601, 612, 633, 634, 640 Lymphatic, 565, 589, 599, 603, 645, 647, 654 Lymphatic system, 599, 645, 647, 654 Lymphoblastic, 304, 600 Lymphoblasts, 520, 600 Lymphocyte, 30, 159, 185, 197, 528, 594, 600, 601 Lymphoid, 52, 60, 527, 596, 600, 629, 654 Lymphoma, 132, 140, 171, 179, 274, 275, 281, 304, 305, 309, 310, 497, 600, 624 Lymphopenia, 31, 600 Lymphoproliferative, 52, 600, 620, 658 Lysine, 431, 584, 600 M Macrophage, 190, 590, 600 Macula, 600 Macula Lutea, 600 Macular Degeneration, 375, 600 Magnetic Resonance Imaging, 313, 600, 640 Magnetic Resonance Spectroscopy, 68, 600 Maintenance therapy, 7, 306, 308, 600 Malabsorption, 471, 497, 600 Malaise, 600 Malignant, 19, 46, 48, 52, 81, 108, 169, 400, 401, 412, 479, 497, 528, 530, 571, 576, 600, 607, 609, 616, 634, 640, 652 Malignant meningioma, 46, 600 Malignant tumor, 400, 401, 412, 600, 607, 616 Malingering, 305, 600 Malnutrition, 494, 522, 531, 539, 600, 607 Mammary, 123, 156, 229, 476, 600, 635, 652 Mammography, 17, 600 Manic, 598, 600 Manifest, 42, 532, 601, 648 Man-made, 542, 601 Mannans, 574, 601 Mannitol, 53, 601 Mastectomy, 601, 634 Mastication, 198, 601, 658 Mastocytosis, 231, 601
Maternal Behavior, 222, 601 Matrix metalloproteinase, 51, 118, 145, 250, 601 Meat, 174, 601 Meatus, 9, 601, 660 Mechanical ventilation, 70, 538, 601 Medial, 65, 350, 527, 530, 569, 570, 601, 614, 646 Median Nerve, 542, 601 Mediastinum, 601, 654 Mediator, 16, 55, 71, 106, 238, 404, 430, 590, 601, 643 Medical Records, 305, 601, 638 Medical Staff, 561, 601 MEDLINE, 6, 493, 496, 498, 602 Medroxyprogesterone, 76, 343, 602 Medroxyprogesterone Acetate, 76, 343, 602 Meibomian, 45, 240, 602 Meibomian Glands, 45, 602 Meiosis, 71, 432, 602, 651, 653, 659 Melanin, 593, 602, 623, 659 Melanocytes, 602 Melanoma, 81, 213, 497, 537, 602 Melengestrol Acetate, 351, 602 Membrane Glycoproteins, 540, 545, 602 Membrane Proteins, 543, 598, 602 Membranoproliferative, 211, 602 Menarche, 602 Meninges, 544, 554, 562, 600, 602 Meningioma, 602 Meningitis, 162, 277, 281, 593, 602 Menorrhagia, 74, 602 Menstruation, 51, 54, 118, 420, 446, 524, 557, 562, 574, 599, 602, 603, 614, 629 Mental Disorders, 319, 342, 603, 629, 632 Mental Health, iv, 10, 245, 319, 492, 494, 495, 503, 603, 629, 633 Mental Retardation, 101, 499, 603 Mentors, 69, 603 Mercaptopurine, 139, 470, 603 Mercury, 360, 603 Mesenchymal, 272, 567, 603 Mesenteric, 603, 627 Mesoderm, 603, 658 Mesolimbic, 46, 603 Meta-Analysis, 4, 154, 161, 603 Metabolic disorder, 559, 603 Metabolite, 11, 41, 142, 536, 560, 568, 603, 624, 629, 635 Metabotropic, 603, 635 Metamorphosis, 105, 401, 603, 613
684 Steroids
Metaphase, 71, 603, 653, 659 Metastasis, 139, 365, 543, 601, 603 Metastatic, 229, 425, 603, 641 Methanol, 201, 326, 349, 419, 428, 429, 604 Methionine, 534, 560, 604, 630, 650 Methoxsalen, 604, 624 Methoxychlor, 604 Methyltestosterone, 200, 604 Metronidazole, 472, 604 Micelle, 428, 604 Miconazole, 6, 604 Microbe, 604, 656 Microbiological Techniques, 359, 604 Microbiology, 99, 383, 461, 520, 532, 533, 604 Microcirculation, 598, 604, 625 Microdialysis, 37, 78, 91, 103, 604 Microorganism, 343, 366, 367, 374, 379, 384, 548, 604, 620, 663 Micro-organism, 557, 580, 604 Microscopy, 22, 106, 124, 225, 417, 533, 604 Microsomal, 58, 604 Middle Cerebral Artery, 91, 109, 605 Mifepristone, 133, 292, 478, 605 Migration, 58, 76, 368, 605 Milliliter, 537, 605, 646 Mineralization, 29, 605 Mineralocorticoid, 106, 127, 330, 426, 438, 605 Mitochondria, 60, 90, 109, 127, 605, 615, 664 Mitochondrial Swelling, 605, 609 Mitosis, 370, 529, 605 Mitotic, 569, 605, 606 Mixed Function Oxidases, 556, 605 Mobility, 605 Mobilization, 71, 398, 540, 605 Modeling, 16, 51, 57, 69, 605 Modification, 75, 104, 122, 324, 353, 357, 567, 576, 605, 633, 664 Modulator, 27, 33, 39, 54, 86, 605 Molecular Conformation, 64, 605 Molecular Structure, 39, 64, 423, 455, 606, 658 Monitor, 35, 74, 97, 233, 252, 307, 312, 313, 346, 421, 554, 606, 612 Monoamine, 65, 91, 103, 525, 559, 606, 641, 659 Monoamine Oxidase, 525, 559, 606, 641, 659 Monoclonal, 108, 112, 146, 195, 317, 556, 584, 587, 593, 606, 634, 664
Monoclonal antibodies, 146, 556, 587, 606 Monocyte, 148, 416, 606 Mononuclear, 187, 571, 579, 606, 658 Monotherapy, 606 Mood Disorders, 68, 176, 606 Morphine, 53, 73, 95, 606, 608, 614 Morphogenesis, 274, 606 Morphological, 26, 39, 70, 75, 93, 522, 564, 574, 602, 606 Morphology, 26, 36, 90, 94, 107, 113, 118, 542, 606 Morula, 536, 606 Moths, 606 Motility, 588, 606, 643 Motor Endplate, 112, 606 Mucins, 606, 639 Mucociliary, 607, 644 Mucosa, 361, 566, 575, 599, 607, 608, 630, 648, 649, 650 Mucositis, 607, 654 Mucus, 368, 411, 412, 570, 607, 659 Multicenter study, 151, 607 Multidose, 162, 607 Multidrug resistance, 274, 607 Multiple Myeloma, 308, 309, 607 Multiple Organ Failure, 607 Multiple sclerosis, 99, 129, 199, 230, 607, 615 Muscle Fatigue, 112, 607 Muscle Fibers, 202, 607, 608 Muscle Relaxation, 607, 610 Muscular Atrophy, 497, 607 Muscular Dystrophies, 562, 607 Musculoskeletal System, 607, 615 Mutagen, 607 Mutagenesis, 60, 182, 607 Mutagenic, 417, 523, 608 Myasthenia, 127, 242, 254, 608 Mycophenolate mofetil, 130, 138, 142, 152, 153, 177, 190, 195, 205, 608 Mydriatic, 560, 608 Myelin, 607, 608, 642 Myeloid Cells, 31, 608 Myeloma, 308, 608 Myocardial infarction, 171, 205, 396, 553, 604, 608 Myocardium, 163, 604, 608 Myoglobin, 608 Myometrium, 149, 169, 177, 608 Myopathy, 131, 152, 226, 482, 608 Myosin, 539, 608 Myotonic Dystrophy, 497, 608
Index 685
N Naive, 37, 306, 309, 315, 608 Naloxone, 534, 608 Narcolepsy, 559, 566, 608 Narcosis, 582, 608 Narcotic, 73, 519, 606, 608 Nasal Cavity, 608, 619, 663 Nasal Septum, 608, 663 Nasogastric, 566, 608 Nasopharynx, 365, 608 Natriuresis, 526, 608 Natural killer cells, 160, 608 Nausea, 575, 588, 609, 619, 629, 652, 659 NCI, 1, 34, 251, 309, 310, 318, 491, 547, 609 Neck Injuries, 446, 609 Necrosis, 307, 365, 505, 529, 537, 553, 565, 571, 576, 588, 604, 608, 609, 637, 638, 640, 643 Needle Sharing, 473, 474, 609 Needlestick Injuries, 475, 609 Neonatal, 136, 142, 152, 177, 184, 186, 189, 206, 315, 316, 588, 609 Neonatal period, 142, 609 Neonatologist, 221, 609 Neoplasia, 64, 462, 497, 569, 609 Neoplasm, 308, 554, 609, 646, 659 Neoplastic, 412, 584, 600, 609, 657 Neostriatum, 542, 609 Nephritis, 60, 225, 239, 609 Nephron, 5, 183, 577, 609 Nephropathy, 9, 148, 226, 236, 240, 594, 609 Nephrosis, 307, 609 Nephrotic, 5, 8, 9, 10, 48, 185, 211, 309, 597, 609 Nephrotic Syndrome, 8, 9, 10, 48, 185, 309, 597, 609 Nerve Endings, 610, 612 Nerve Growth Factor, 37, 610 Neural Pathways, 84, 610 Neuritis, 148, 610, 615, 662 Neuroanatomy, 36, 597, 610 Neurobehavioral Manifestations, 538, 559, 610 Neuroblastoma, 230, 610 Neurodegenerative Diseases, 120, 533, 610 Neuroendocrinology, 68, 102, 105, 157, 456, 610 Neurologic, 538, 577, 584, 610 Neuromuscular, 112, 204, 303, 306, 309, 519, 610, 618, 627 Neuromuscular Blockade, 204, 610
Neuromuscular Junction, 112, 519, 610 Neuropathy, 201, 611, 640, 664 Neuropeptide, 30, 54, 65, 68, 116, 553, 611 Neuropharmacology, 69, 164, 198, 208, 249, 265, 611 Neuroprotective Agents, 109, 611 Neurosciences, 92, 207, 244, 456, 611 Neurosecretory Systems, 565, 611 Neurotoxic, 28, 611 Neurotoxicity, 28, 611 Neurotransmitters, 84, 451, 524, 569, 611 Neutralization, 112, 611 Neutrons, 523, 537, 593, 611, 634 Neutropenia, 416, 611 Neutrophil, 95, 416, 611 Niacin, 611, 658 Nickel, 254, 400, 611 Nicotine, 446, 611 Nidation, 564, 611 Nifedipine, 142, 611 Nitric Oxide, 54, 70, 71, 111, 161, 169, 367, 368, 456, 478, 612 Nitriles, 555, 612 Nitrogen, 347, 432, 523, 524, 526, 555, 568, 570, 573, 578, 584, 594, 612, 615, 658 Nociceptors, 95, 612 Node-negative, 19, 612 Nonmalignant, 365, 612 Norepinephrine, 21, 65, 103, 126, 521, 561, 566, 612 Norgestrel, 596, 612 Norsteroids, 330, 397, 419, 612 Novobiocin, 433, 612 Nuclear Family, 571, 612 Nuclear Medicine, 12, 55, 164, 233, 612 Nuclear Proteins, 612 Nucleic acid, 19, 416, 425, 426, 435, 438, 576, 584, 588, 612, 613, 614, 633, 639, 663, 664 Nucleic Acid Hybridization, 584, 613 Nucleoproteins, 612, 613 Nucleus, 26, 45, 65, 68, 93, 94, 103, 104, 333, 335, 336, 367, 371, 374, 396, 398, 399, 411, 436, 437, 438, 439, 529, 532, 533, 546, 555, 556, 558, 563, 566, 569, 574, 591, 602, 606, 611, 612, 613, 630, 632, 648, 650, 653, 662 Nucleus Accumbens, 45, 103, 613 Nutritional Support, 220, 575, 613 Nymph, 603, 613 O Observational study, 74, 613
686 Steroids
Occult, 152, 613 Ocular, 45, 213, 254, 263, 339, 340, 342, 347, 364, 375, 553, 568, 570, 613 Ocular Hypertension, 339, 340, 342, 364, 613 Odour, 372, 393, 394, 395, 530, 613 Oestradiol, 414, 437, 438, 613 Oestrogen, 154, 157, 414, 429, 437, 438, 613 Ointments, 83, 354, 361, 402, 613, 619 Olfactory Bulb, 350, 613, 663 Oligomenorrhea, 614, 626 Oligonucleotide Probes, 614 Oliguria, 594, 601, 614 Oncogene, 497, 582, 614 Oncogenic, 590, 614 On-line, 156, 517, 614 Oocytes, 59, 71, 109, 121, 157, 173, 432, 614 Oophorectomy, 614, 651 Oophoritis, 307, 614 Opacity, 542, 557, 614 Operon, 614, 630, 637 Ophthalmic, 340, 342, 364, 375, 376, 484, 486, 487, 614 Ophthalmologic, 364, 562, 614 Ophthalmology, 184, 203, 213, 214, 218, 246, 253, 254, 257, 258, 573, 614 Opioid Peptides, 97, 562, 565, 614 Opium, 606, 614 Opportunistic Infections, 474, 614 Optic Chiasm, 586, 614, 615, 629, 650 Optic cup, 615, 620 Optic disc, 615 Optic Disk, 559, 600, 615 Optic Nerve, 375, 524, 614, 615, 618, 620, 638, 640 Optic Neuritis, 221, 264, 615 Oral Health, 447, 615 Orbit, 615 Orbital, 148, 246, 615 Orchiectomy, 322, 327, 363, 615, 651 Organ Culture, 11, 299, 615, 655 Organelles, 544, 556, 602, 615 Organic Chemicals, 431, 615 Organotin Compounds, 400, 401, 615 Oropharynx, 585, 615 Orthopaedic, 258, 506, 615 Osmium Tetroxide, 381, 615 Osmolarity, 601, 615 Osmosis, 616 Osmotic, 53, 140, 522, 593, 605, 616, 643 Osmotic Fragility, 140, 616 Ossification, 616, 639
Osteoarthritis, 191, 281, 369, 427, 480, 616 Osteoblasts, 29, 32, 224, 616 Osteocalcin, 29, 616 Osteoclasts, 11, 616 Osteocytes, 29, 616 Osteogenic sarcoma, 616 Osteonecrosis, 241, 616 Osteosarcoma, 71, 616 Otitis, 80, 215, 243, 616 Otitis Media, 80, 215, 243, 616 Otitis Media with Effusion, 215, 243, 616 Ouabain, 58, 616, 649 Outpatient, 80, 314, 478, 616 Ovarian epithelial cancer, 309, 617 Ovarian Follicle, 84, 553, 574, 579, 617 Ovariectomy, 37, 46, 617 Ovary, 48, 274, 346, 412, 414, 526, 553, 568, 578, 613, 614, 617, 626, 649 Overdose, 552, 617 Ovulation, 85, 212, 307, 357, 432, 434, 527, 548, 562, 574, 579, 599, 612, 617 Ovum, 173, 432, 553, 557, 574, 576, 597, 606, 617, 629, 630, 658, 664, 665 Ovum Implantation, 617, 658 Oxandrolone, 34, 302, 617 Oxidants, 431, 617 Oxidation-Reduction, 536, 617 Oxidative metabolism, 521, 596, 617 Oxidative Stress, 19, 39, 61, 617 Oxides, 326, 617 Oxygen Consumption, 570, 617, 637 Oxygenation, 586, 617 Oxygenator, 541, 618 Oxytocin, 65, 217, 263, 618 P Pacemaker, 150, 618 Pachymeningitis, 602, 618 Pain Threshold, 54, 618 Palate, 608, 618, 648 Palladium, 329, 618 Palliative, 30, 250, 251, 555, 613, 618, 653 Palliative therapy, 30, 618 Palsy, 142, 222, 277, 507, 618, 646 Pamidronate, 316, 618 Pancreas Transplant, 130, 190, 195, 618 Pancreas Transplantation, 190, 195, 618 Pancreatic, 497, 554, 618 Pancreatic cancer, 497, 618 Pancuronium, 237, 618 Panic, 342, 618 Panic Disorder, 342, 618 Par excellence, 31, 619
Index 687
Paraesthesia, 337, 338, 619 Paraffin, 402, 619 Paralysis, 204, 237, 519, 555, 568, 581, 619, 646 Paranasal Sinuses, 619, 644 Parasite, 619, 657 Parasitic, 274, 554, 619 Parathyroid, 29, 35, 619, 639, 653 Parathyroid Glands, 619, 639 Parathyroid hormone, 29, 35, 619 Parenchyma, 47, 619 Parenteral, 7, 215, 619, 642 Parenteral Nutrition, 619, 642 Paresis, 610, 619 Paresthesias, 610, 619 Parotid, 620, 640 Paroxysmal, 497, 568, 620, 622, 664 Partial remission, 620, 636 Particle, 257, 380, 601, 604, 620, 646, 656, 663 Parturition, 54, 85, 207, 218, 263, 316, 620, 630 Patch, 15, 22, 391, 408, 427, 596, 620, 656 Pathogen, 415, 588, 620 Pathogenesis, 45, 61, 70, 78, 79, 111, 113, 332, 362, 445, 620 Pathologic, 445, 519, 529, 535, 540, 553, 585, 620, 632, 637, 643 Pathologic Processes, 529, 620 Pathologies, 61, 365, 620 Pathophysiology, 8, 25, 48, 55, 59, 64, 68, 78, 79, 118, 474, 620 Patient Education, 504, 512, 514, 517, 620 Patient Selection, 193, 620 Pedicle, 226, 620 Pelvic, 118, 565, 620, 631 Pemphigus, 361, 519, 620 Penicillin, 12, 431, 527, 620 Penis, 9, 79, 116, 533, 563, 620, 623, 629, 637 Pentosan polysulfate, 446, 620 Pentostatin, 304, 620 Pepsin, 620, 621 Pepsin A, 620, 621 Peptic, 8, 64, 282, 621 Peptic Ulcer, 8, 64, 282, 621 Peracetic Acid, 326, 349, 621 Perception, 18, 26, 94, 304, 558, 621, 640 Percutaneous, 427, 457, 621, 623 Perforation, 45, 574, 621, 656 Perfusion, 15, 53, 586, 621 Pericarditis, 157, 282, 621
Pericardium, 621, 652 Perimenopausal, 56, 96, 621 Perinatal, 107, 130, 181, 204, 248, 368, 588, 621 Perineal, 445, 621 Perineum, 621 Periodicity, 621, 639 Peripheral blood, 27, 30, 372, 393, 394, 395, 581, 590, 621, 624 Peripheral Nerves, 596, 621, 647 Peripheral Nervous System, 174, 610, 618, 621, 640, 650 Peripheral stem cells, 579, 621 Peritoneal, 118, 258, 622 Peritoneal Cavity, 118, 622 Peritoneum, 622, 638 Perivascular, 51, 622 Periventricular Leukomalacia, 136, 622 Peroxide, 622 Peroxisome Proliferators, 80, 622 Pertussis, 234, 282, 622, 664 Pesticides, 535, 589, 622 Petroleum, 575, 619, 622 PH, 127, 161, 171, 183, 186, 334, 433, 537, 622 Phagocyte, 617, 622 Phagocytosis, 28, 148, 622 Pharmaceutical Preparations, 336, 341, 345, 410, 544, 569, 575, 622, 630 Pharmacodynamics, 260, 622 Pharmacogenetics, 622 Pharmacokinetic, 623 Pharmacologic, 86, 110, 112, 526, 532, 554, 580, 623, 656 Pharyngitis, 130, 623 Pharynx, 585, 608, 615, 623, 660 Phenobarbital, 116, 623 Phenotype, 13, 29, 36, 42, 52, 60, 111, 623, 657 Phenyl, 323, 331, 334, 369, 396, 623 Phenylacetate, 334, 623 Phenylalanine, 621, 623, 659 Pheromone, 329, 349, 358, 371, 393, 394, 395, 623 Phimosis, 9, 199, 254, 623 Phonophoresis, 593, 623 Phorbol, 623 Phorbol Esters, 623 Phosphates, 623 Phosphodiesterase, 367, 623 Phospholipases, 623, 644 Phospholipids, 571, 598, 623
688 Steroids
Phosphoric Acids, 334, 623 Phosphorous, 428, 623 Phosphorus, 397, 405, 540, 615, 619, 623 Phosphorylated, 52, 87, 548, 623 Phosphorylation, 52, 63, 87, 623 Photoaffinity Labels, 57, 624 Photochemotherapy, 148, 624 Photocoagulation, 548, 624 Photodynamic therapy, 12, 235, 624 Photoperiod, 26, 624 Photopheresis, 305, 624 Photosensitizing Agents, 624 Phototherapy, 148, 444, 624 Physical Examination, 305, 311, 313, 446, 624 Physical Fitness, 40, 624, 647 Pigment, 213, 535, 599, 602, 608, 624 Pilot study, 8, 34, 50, 55, 104, 147, 160, 230, 264, 303, 306, 624 Pineal Body, 624 Pineal gland, 100, 624 Pituitary Gland, 412, 553, 572, 578, 624, 630 Placenta, 79, 109, 116, 299, 346, 410, 530, 568, 572, 573, 624, 629, 659 Plana, 625, 643 Plant Growth Regulators, 580, 625 Plaque, 28, 545, 625 Plasma cells, 527, 607, 608, 625 Plasma Exchange, 195, 235, 252, 257, 625 Plasma protein, 410, 522, 565, 574, 625, 643 Plasma Volume, 605, 625 Plasmapheresis, 48, 147, 625 Plasmids, 424, 425, 625 Plasmin, 625, 655, 660 Plasminogen, 210, 228, 343, 625, 655, 660 Plasminogen Activators, 228, 625 Plasticity, 26, 38, 75, 92, 98, 120, 176, 221, 264, 625 Platelet Activation, 368, 626, 644 Platelet Aggregation, 525, 560, 612, 626, 654 Platelet Aggregation Inhibitors, 560, 626 Platelets, 193, 529, 612, 626, 654 Platinum, 111, 329, 547, 599, 618, 626 Pleomorphic, 613, 626 Pneumoconiosis, 626, 644 Podophyllotoxin, 569, 626 Poisoning, 273, 539, 575, 591, 603, 609, 626 Pollen, 186, 626 Polyarteritis Nodosa, 195, 312, 586, 626 Polyarthritis, 594, 626, 643
Polycystic, 48, 67, 84, 87, 89, 90, 165, 181, 185, 498, 509, 585, 626 Polycystic Ovary Syndrome, 87, 165, 181, 509, 585, 626 Polymerase, 433, 626, 627, 630, 637 Polymerase Chain Reaction, 433, 627 Polymers, 357, 627, 632 Polymorphic, 557, 627 Polymorphism, 42, 153, 627 Polymyalgia Rheumatica, 155, 627 Polymyxin, 433, 486, 627 Polyp, 137, 627 Polypeptide, 456, 524, 549, 551, 567, 572, 584, 608, 620, 625, 627, 630, 653, 665 Polyposis, 144, 204, 549, 627 Polysaccharide, 528, 544, 627, 632, 660 Popliteal, 250, 627 Portal Vein, 311, 627 Posterior, 525, 531, 533, 544, 546, 561, 593, 615, 618, 624, 627, 640, 646 Postnatal, 15, 44, 46, 70, 79, 88, 91, 101, 112, 151, 200, 221, 248, 262, 263, 507, 627, 648 Postoperative, 218, 252, 257, 258, 474, 607, 627 Postsynaptic, 15, 59, 76, 82, 606, 627, 644, 651 Post-synaptic, 44, 72, 627 Post-translational, 87, 90, 526, 627, 643 Post-traumatic, 113, 538, 627 Potassium, 21, 84, 161, 269, 345, 392, 429, 446, 522, 605, 628 Potassium hydroxide, 429, 628 Potentiate, 104, 109, 628 Potentiation, 68, 82, 116, 599, 628, 644 Poultice, 427, 628 Practice Guidelines, 495, 506, 628 Precancerous, 545, 628 Precipitation, 348, 628 Preclinical, 69, 628 Predictive factor, 10, 628 Predisposition, 42, 628 Prednisolone, 4, 31, 106, 125, 308, 359, 377, 388, 469, 628 Prednisone, 83, 106, 307, 310, 312, 316, 377, 388, 421, 469, 505, 628 Preeclampsia, 410, 628 Pre-Eclampsia, 118, 628 Pregnancy Maintenance, 628 Pregnanes, 335, 336, 344, 371, 397, 628, 629 Pregnanolone, 33, 109, 207, 628 Pregnenes, 333, 371, 390, 629
Index 689
Premenopausal, 34, 42, 74, 133, 142, 152, 153, 317, 440, 629 Premenstrual, 56, 68, 115, 155, 197, 208, 223, 629 Premenstrual Syndrome, 155, 629 Prenatal, 90, 161, 165, 235, 564, 629 Preoptic Area, 66, 107, 629 Prepuce, 547, 623, 629 Presynaptic, 72, 606, 610, 629, 651 Prevalence, 8, 23, 55, 223, 228, 250, 300, 629 Prickle, 519, 594, 629 Primary central nervous system lymphoma, 310, 629 Primary Prevention, 16, 629 Probe, 25, 58, 63, 98, 479, 604, 614, 629 Proctosigmoiditis, 469, 629 Prodrug, 31, 629, 635 Proestrus, 629 Progeny, 551, 629 Progression, 5, 43, 313, 314, 425, 445, 527, 629, 641 Progressive, 5, 48, 225, 304, 368, 530, 543, 546, 553, 557, 561, 568, 579, 592, 594, 607, 608, 609, 610, 616, 626, 629, 636, 659 Progressive disease, 304, 629 Proinsulin, 210, 554, 629, 633 Projection, 557, 591, 612, 613, 615, 630, 633, 636 Prolactin, 75, 113, 630 Proline, 549, 584, 630 Promoter, 49, 76, 77, 225, 438, 439, 630 Promotor, 630, 638 Prone, 9, 40, 630 Pro-Opiomelanocortin, 565, 614, 630 Prophase, 71, 432, 614, 630, 651, 653, 659 Prophylaxis, 7, 8, 132, 188, 368, 396, 569, 630, 660 Propylene Glycol, 402, 630 Prosencephalon, 559, 630, 652 Prospective Studies, 630 Prospective study, 251, 253, 598, 630 Prostaglandin, 64, 107, 144, 217, 218, 420, 526, 555, 626, 630, 631, 654 Prostaglandin-Endoperoxide Synthase, 555, 631 Prostaglandins A, 588, 630, 631 Prostaglandins F, 605, 631 Prostate gland, 88, 332, 362, 631 Prostatic Hyperplasia, 631 Prostatic Neoplasms, 568, 631 Protease, 57, 70, 549, 631, 655
Protease Inhibitors, 631 Protein Binding, 49, 631 Protein C, 522, 524, 529, 533, 593, 597, 616, 631, 659 Protein Isoforms, 523, 631 Protein Kinases, 39, 632 Protein S, 12, 19, 20, 59, 63, 423, 467, 498, 536, 551, 568, 576, 616, 632, 639, 649 Proteinuria, 5, 43, 310, 577, 602, 607, 609, 628, 632 Proteoglycans, 533, 570, 632 Proteolytic, 19, 549, 572, 625, 632, 655, 660 Protocol, 5, 21, 32, 34, 134, 234, 632 Protons, 523, 584, 592, 600, 632, 634 Protozoa, 551, 604, 632 Proximal, 49, 75, 226, 469, 561, 608, 627, 629, 632, 642 Pruritic, 562, 597, 632 Psoralen, 444, 632 Psoriasis, 31, 170, 282, 365, 369, 444, 505, 527, 548, 569, 624, 632 Psychiatric, 107, 108, 208, 226, 310, 342, 446, 503, 603, 632, 644 Psychic, 596, 632, 641 Psychogenic, 632 Psychomotor, 44, 632 Psychoneuroimmunology, 28, 632 Psychotomimetic, 525, 559, 632 Public Health, 32, 55, 132, 223, 250, 401, 494, 495, 633 Public Policy, 493, 633 Publishing, 6, 121, 350, 351, 445, 633 Pulmonary Artery, 536, 633, 661 Pulmonary Circulation, 70, 633 Pulmonary Edema, 368, 545, 594, 633 Pulmonary hypertension, 368, 552, 633 Pulmonary Sarcoidosis, 210, 633 Pulse, 44, 58, 84, 106, 155, 227, 229, 253, 310, 479, 482, 506, 606, 633 Pupa, 603, 633 Pupil, 539, 552, 560, 608, 615, 633 Purified Insulins, 630, 633 Purines, 633, 643 Purpura, 235, 252, 633 Purulent, 519, 565, 633, 660 Pustular, 444, 519, 633 Pyramidal Cells, 558, 633 Q Quality of Life, 17, 21, 24, 51, 100, 104, 115, 244, 310, 314, 445, 618, 633 Quaternary, 273, 347, 618, 633
690 Steroids
R Race, 10, 102, 522, 561, 596, 605, 612, 634 Radiation therapy, 81, 229, 310, 540, 570, 591, 593, 620, 634, 664 Radical mastectomy, 407, 634 Radiculopathy, 634, 640 Radioactivity, 354, 634 Radioimmunoassay, 237, 355, 457, 634 Radioimmunotherapy, 634, 635 Radioisotope, 614, 634, 656 Radiolabeled, 57, 58, 537, 593, 634, 664 Radiological, 355, 621, 634 Radiology, 55, 168, 190, 198, 314, 612, 634 Radiotherapy, 229, 245, 252, 537, 593, 634, 664 Raloxifene, 34, 635, 641 Ramipril, 226, 635 Randomized clinical trial, 24, 130, 635 Randomized Controlled Trials, 80, 469, 635 Reabsorption, 635 Reaction Time, 377, 635 Reactivation, 274, 635 Reactive Oxygen Species, 396, 635 Reagent, 81, 329, 353, 377, 382, 390, 397, 430, 545, 584, 599, 635 Receptivity, 66, 103, 635 Receptors, Glutamate, 635 Receptors, Serotonin, 636, 643 Recombinant, 15, 24, 40, 57, 77, 190, 200, 202, 203, 315, 435, 636, 661 Recombination, 551, 576, 636 Reconstitution, 45, 636 Recovery of Function, 113, 636 Rectum, 469, 529, 537, 549, 559, 560, 573, 575, 588, 589, 595, 629, 631, 636, 644 Recurrence, 161, 240, 247, 312, 545, 547, 621, 636 Red blood cells, 305, 568, 581, 636 Red Nucleus, 531, 636 Reflex, 95, 118, 134, 249, 636 Reflux, 390, 636 Refraction, 527, 636, 646 Refractive Errors, 524, 636 Refractory, 229, 304, 308, 315, 421, 469, 563, 636 Regeneration, 38, 353, 572, 636 Relapse, 4, 7, 9, 10, 43, 85, 185, 310, 426, 446, 477, 636 Relaxant, 54, 636 Remission, 5, 7, 9, 10, 43, 48, 104, 305, 307, 310, 312, 445, 446, 469, 471, 600, 636
Remission Induction, 104, 636 Renal failure, 43, 636 Renin, 42, 68, 526, 637 Renin-Angiotensin System, 526, 637 Reperfusion, 53, 62, 637 Reperfusion Injury, 637 Repressor, 90, 614, 637 Reproductive cells, 576, 637 Reproductive system, 89, 434, 631, 637 Research Design, 637 Resection, 48, 139, 198, 226, 301, 471, 637 Resorption, 584, 616, 635, 637 Respiration, 368, 529, 541, 552, 555, 606, 637, 638 Respirator, 601, 637, 661 Respiratory distress syndrome, 137, 316, 368, 396, 538, 637 Respiratory failure, 71, 637, 661 Respiratory Physiology, 139, 146, 165, 179, 189, 204, 210, 259, 637, 661 Respiratory syncytial virus, 242, 637 Response Elements, 81, 426, 427, 637 Response rate, 471, 638 Restoration, 635, 636, 637, 638, 664 Resuscitation, 236, 638 Retina, 546, 547, 559, 596, 600, 614, 615, 633, 638, 639, 643 Retinal, 559, 614, 615, 638, 663 Retinal Ganglion Cells, 615, 638 Retinoblastoma, 497, 638 Retinoid, 569, 638 Retinopathy, 8, 559, 638 Retrobulbar, 615, 638 Retrograde, 592, 638 Retroperitoneal, 236, 521, 638, 663 Retrospective, 5, 10, 51, 236, 638 Retrospective study, 10, 638 Retrovirus, 638 Rhabdomyolysis, 168, 169, 638 Rhamnose, 616, 638 Rheumatism, 224, 586, 638, 639 Rhinitis, 466, 538, 566, 639 Rhythmicity, 96, 639 Ribonuclease, 11, 639 Ribonucleic acid, 156, 639 Ribose, 520, 639, 654 Ribosome, 639, 657 Rickets, 371, 639, 663 Rigidity, 625, 639 Risk factor, 10, 19, 32, 97, 100, 141, 144, 212, 237, 333, 446, 505, 630, 639 Risk-Taking, 101, 639
Index 691
Rod, 533, 547, 639 Rosiglitazone, 639 Rubber, 520, 639 S Salicylate, 91, 639 Saline, 625, 639 Saliva, 34, 372, 393, 394, 395, 461, 639 Salivary, 17, 34, 106, 241, 556, 559, 618, 639, 643, 645, 650, 664 Salivary glands, 106, 556, 559, 639, 643, 645 Saponin, 272, 639 Sarcoidosis, 189, 283, 640 Satellite, 453, 455, 640 Scalpel, 205, 640 Scans, 21, 640 Scatter, 52, 640 Schematic, 471, 640 Schizoid, 640, 664 Schizophrenia, 108, 120, 640, 664 Schizotypal Personality Disorder, 558, 640, 664 Schwannoma, 223, 640 Sciatica, 166, 640 Sclera, 530, 546, 551, 640 Scleroderma, 283, 530, 571, 640 Sclerosis, 48, 281, 498, 530, 549, 607, 640 Scrotum, 640, 653, 660 Sebaceous, 602, 640, 641, 662, 663 Sebaceous gland, 602, 641, 662, 663 Seborrhea, 332, 362, 641 Sebum, 413, 519, 640, 641 Second Messenger Systems, 611, 635, 641 Secondary tumor, 603, 641 Secosteroids, 341, 641 Secretory, 411, 412, 554, 641, 651 Sedative, 33, 100, 110, 533, 573, 628, 641 Sedatives, Barbiturate, 641 Sedentary, 112, 641 Sediment, 641, 660 Segmental, 5, 43, 48, 136, 173, 307, 309, 310, 577, 641, 646 Segmentation, 641 Segregation, 533, 636, 641 Seizures, 81, 104, 108, 577, 620, 641 Selective estrogen receptor modulator, 635, 641, 652 Selegiline, 158, 641 Selenious Acid, 390, 642 Selenium, 269, 328, 345, 390, 391, 431, 642 Self Administration, 62, 642 Self Care, 520, 642
Sella, 561, 624, 642 Semen, 160, 248, 532, 563, 631, 642 Semicircular canal, 589, 642 Seminal vesicles, 642, 660 Seminiferous Epithelium, 642 Seminiferous tubule, 526, 589, 642, 646 Semisynthetic, 541, 569, 587, 642 Senile, 616, 642 Sensibility, 525, 585, 642 Sensitization, 46, 62, 84, 103, 169, 333, 440, 642 Sensory loss, 634, 642, 646, 653 Sepsis, 28, 126, 236, 244, 265, 368, 642 Septal, 597, 642 Septic, 224, 243, 264, 339, 340, 343, 364, 376, 530, 642 Septum, 66, 642 Septum Pellucidum, 642 Sequencing, 627, 642 Sequester, 642, 651 Serine, 77, 87, 565, 643, 655 Serologic, 587, 643 Serous, 140, 565, 643 Serrata, 286, 547, 643 Serrated, 643 Sertraline, 115, 643 Serum Albumin, 417, 634, 643 Sex Behavior, 599, 643 Sex Behavior, Animal, 599, 643 Sex Characteristics, 520, 526, 613, 633, 643, 653 Sex Determination, 36, 498, 643 Sex Differentiation, 116, 643 Sex Hormone-Binding Globulin, 144, 643 Sharpness, 643, 663 Shoulder Pain, 479, 643 Sicca, 347, 643 Side effect, 4, 5, 6, 9, 16, 21, 60, 82, 111, 180, 185, 250, 271, 305, 307, 308, 310, 311, 312, 322, 327, 337, 338, 363, 370, 392, 402, 421, 422, 427, 469, 470, 471, 474, 482, 483, 488, 494, 505, 506, 521, 535, 555, 585, 644, 656, 664 Sigmoid, 469, 629, 644 Sigmoid Colon, 469, 629, 644 Signal Transduction, 20, 23, 68, 78, 107, 539, 543, 644 Signs and Symptoms, 474, 626, 636, 644 Silanes, 322, 644 Silicon, 644 Silicosis, 225, 644 Sinusitis, 80, 223, 283, 312, 644
692 Steroids
Sitosterols, 384, 644 Skeletal, 32, 34, 79, 124, 259, 526, 547, 554, 555, 607, 638, 644, 646 Skeleton, 32, 35, 265, 323, 373, 385, 390, 396, 419, 432, 520, 571, 583, 585, 593, 630, 644 Skull, 554, 615, 619, 644, 652 Sleep apnea, 100, 205, 644, 649 Sleep Deprivation, 187, 644 Small intestine, 61, 534, 545, 547, 562, 566, 576, 583, 586, 591, 608, 644 Smooth Muscle Tumor, 74, 572, 645 Snake Venoms, 560, 645 Sneezing, 622, 645, 649 Social Behavior, 24, 79, 645, 663 Social Environment, 633, 645 Sodium Acetate, 349, 429, 645 Soft tissue, 446, 537, 571, 572, 609, 644, 645 Soft Tissue Injuries, 446, 645 Solid tumor, 526, 565, 645 Solvent, 241, 326, 347, 348, 354, 355, 356, 360, 362, 377, 380, 381, 386, 390, 430, 519, 534, 569, 578, 604, 616, 630, 645 Soma, 22, 70, 633, 645 Somatic, 22, 95, 520, 564, 583, 597, 602, 605, 621, 645, 652, 660 Somatic cells, 602, 605, 645 Songbirds, 18, 26, 67, 92, 102, 645 Sorbitol, 601, 645 Sound wave, 550, 646 Soybean Oil, 380, 646 Spasm, 582, 646, 653 Spasmodic, 539, 622, 646 Spastic, 593, 646 Specialist, 464, 509, 560, 646 Specificity, 25, 47, 61, 64, 81, 107, 120, 241, 355, 521, 530, 540, 565, 646 Spectrometer, 11, 646 Spectrum, 59, 368, 371, 469, 555, 646, 659 Sperm, 60, 131, 160, 273, 433, 526, 546, 552, 626, 637, 642, 646, 653, 661 Sperm Count, 60, 646 Spermatogenesis, 408, 441, 646 Spermatozoa, 432, 532, 642, 646, 660 Sphenoid, 619, 642, 646 Sphincter, 595, 646, 649 Spinal Cord Compression, 229, 646 Spinal Fractures, 646 Spinal Nerve Roots, 634, 640, 646 Spinal Nerves, 621, 647 Spinal tap, 599, 647 Spinous, 567, 594, 647
Spleen, 525, 556, 599, 600, 640, 647 Splenectomy, 177, 219, 647 Splenic Vein, 627, 647 Spondylitis, 175, 647 Sporadic, 610, 638, 647 Sports Medicine, 134, 135, 140, 141, 225, 226, 234, 249, 259, 476, 512, 647 Sprains and Strains, 283, 599, 647 Sputum, 24, 161, 647 Squamous, 235, 647 Stabilizer, 306, 367, 647 Staging, 640, 647 Stagnation, 647, 656 Standard therapy, 624, 647 Stanozolol, 294, 341, 647 Staphylococcal Scalded Skin Syndrome, 231, 647 Statistically significant, 7, 647 Status Asthmaticus, 131, 237, 368, 647 Steady state, 648 Steel, 547, 648 Stem cell transplantation, 188, 228, 581, 648 Stem Cells, 108, 581, 621, 648, 659 Stent, 252, 648 Sterile, 530, 619, 648, 658 Sterility, 129, 145, 160, 161, 165, 173, 175, 224, 236, 555, 589, 648 Sterilization, 48, 504, 648 Steroid therapy, 3, 4, 5, 10, 48, 104, 126, 304, 307, 308, 309, 317, 325, 375, 421, 453, 467, 648 Stimulant, 524, 539, 558, 583, 648 Stimulus, 33, 54, 73, 524, 552, 561, 562, 563, 569, 589, 592, 595, 619, 635, 636, 648, 654 Stomatitis, 361, 648 Stool, 588, 593, 595, 648, 652 Strabismus, 203, 213, 218, 257, 524, 648 Strand, 626, 648 Streptomycin, 254, 431, 648 Streptozocin, 649 Stress urinary, 233, 255, 649 Stria, 65, 106, 649 Stria Vascularis, 106, 649 Striatum, 609, 613, 649 Stricture, 235, 649 Stridor, 554, 649, 653 Stroke, 91, 108, 120, 263, 319, 339, 340, 343, 364, 376, 396, 492, 541, 611, 649 Stroke Volume, 541, 649 Stroma, 86, 553, 593, 619, 649 Stromal, 29, 32, 51, 108, 114, 224, 565, 649
Index 693
Stromal Cells, 51, 108, 224, 649 Strophanthins, 541, 649 Structure-Activity Relationship, 82, 194, 229, 649 Strychnine, 539, 649 Stupor, 596, 608, 649 Subacute, 54, 69, 589, 644, 649 Subclinical, 55, 588, 641, 649 Subcutaneous, 78, 175, 352, 520, 562, 595, 619, 650, 663 Subfornical Organ, 68, 650 Subiculum, 583, 650 Submaxillary, 567, 650 Submucous, 198, 650 Subspecies, 646, 650 Substance P, 568, 603, 636, 641, 648, 650 Substrate, 40, 52, 63, 95, 162, 378, 379, 542, 555, 556, 566, 605, 650, 659 Substrate Specificity, 650 Subtrochanteric, 582, 650 Suction, 572, 650 Sulfotransferases, 650 Sulfur, 325, 328, 329, 570, 595, 604, 615, 650 Sulfuric acid, 650 Sunburn, 283, 650, 659 Superior vena cava, 245, 537, 650 Superoxide, 650 Supplementation, 6, 114, 422, 429, 650 Suppressive, 31, 49, 110, 650 Suprachiasmatic Nucleus, 100, 650 Supraoptic Nucleus, 263, 650 Surfactant, 71, 163, 184, 193, 201, 212, 650 Surgical castration, 411, 651 Survival Rate, 407, 651 Sweat, 641, 651 Sweat Glands, 641, 651 Sympathetic Nervous System, 526, 532, 651 Sympathomimetic, 524, 559, 561, 567, 612, 651, 659 Symphysis, 631, 651 Symptomatic, 55, 74, 115, 125, 168, 315, 421, 651 Synapses, 75, 598, 611, 613, 651 Synapsis, 651 Synaptic, 27, 38, 75, 82, 84, 98, 108, 112, 120, 350, 598, 606, 611, 635, 644, 651 Synaptic Transmission, 82, 112, 611, 635, 651 Synaptic Vesicles, 120, 651
Synergistic, 31, 43, 47, 104, 438, 620, 630, 652, 655 Synovial, 443, 652 Synthetic retinoid, 444, 652 Syrinx, 102, 645, 652 Systemic disease, 46, 652 Systemic lupus erythematosus, 60, 99, 153, 216, 223, 549, 586, 652 Systolic, 585, 652 T Talc, 652 Talus, 527, 652 Tamoxifen, 17, 34, 42, 76, 108, 247, 408, 641, 652 Tamponade, 368, 652 Taurine, 534, 545, 546, 558, 598, 652 Telangiectasia, 498, 652 Telencephalon, 94, 533, 630, 652 Tellurium, 391, 652 Telomerase, 247, 652 Temporal, 25, 63, 92, 97, 103, 155, 221, 445, 525, 583, 600, 601, 619, 627, 652 Temporal Lobe, 25, 525, 652 Tenesmus, 469, 652 Teratogenic, 523, 569, 653 Terminalis, 65, 652, 653 Testicles, 615, 640, 651, 653, 661 Testicular, 31, 59, 90, 107, 111, 157, 300, 309, 411, 465, 506, 530, 653 Testis, 48, 77, 86, 526, 568, 613, 653 Tetanus, 539, 653 Tetany, 619, 653 Tetravalent, 644, 653 Thalamic, 531, 653 Thalamic Diseases, 531, 653 Thalassemia, 534, 653 Theophylline, 149, 633, 653 Therapeutics, 12, 19, 88, 108, 131, 136, 140, 231, 272, 467, 488, 606, 653 Thermal, 54, 371, 527, 537, 560, 611, 627, 653 Thermoregulation, 36, 624, 653 Third Ventricle, 586, 624, 653 Thoracic, 152, 179, 223, 231, 559, 601, 654, 664 Thorax, 149, 161, 171, 186, 188, 213, 225, 230, 235, 246, 519, 599, 650, 654, 660 Threonine, 87, 643, 654 Threshold, 18, 97, 569, 585, 654 Thrombin, 572, 626, 631, 654 Thrombocytes, 626, 654 Thrombocytopenia, 172, 416, 654
694 Steroids
Thromboembolism, 368, 654 Thrombolytic, 625, 654 Thrombomodulin, 631, 654 Thromboses, 257, 654 Thrombosis, 219, 228, 422, 590, 632, 649, 654 Thromboxanes, 530, 555, 563, 654 Thrombus, 205, 553, 588, 626, 654, 661 Thymidine, 38, 58, 232, 538, 654 Thymidine Phosphorylase, 232, 654 Thymidylate Synthase, 247, 654 Thymus, 31, 401, 587, 599, 600, 654 Thymus Gland, 401, 654 Thyroid Gland, 391, 619, 654, 655 Thyroid Hormones, 273, 302, 453, 458, 464, 655, 659 Thyrotropin, 586, 655 Thyroxine, 423, 522, 623, 655 Tic, 65, 655 Tilapia, 220, 655 Tin, 400, 401, 542, 615, 626, 655 Tin Compounds, 401, 655 Tinnitus, 304, 616, 655, 662 Tissue Culture, 22, 108, 262, 431, 655 Tissue Plasminogen Activator, 210, 655 Tolerance, 54, 73, 520, 577, 655 Tome, 287, 295, 655 Tomography, 18, 125, 202, 600, 655 Tonic, 541, 552, 655 Tooth Preparation, 520, 655 Torpor, 13, 656 Torsion, 588, 656 Toxaemia, 628, 656 Toxic, iv, 356, 361, 370, 396, 401, 470, 523, 524, 528, 534, 541, 545, 551, 555, 556, 560, 564, 566, 570, 584, 586, 587, 604, 611, 615, 626, 628, 642, 645, 656, 664 Toxicokinetics, 656 Toxicology, 83, 146, 217, 262, 455, 494, 656 Toxins, 38, 524, 528, 540, 564, 577, 587, 588, 606, 634, 645, 656 Toxoplasmosis, 532, 656 Trabecular Meshwork, 656 Trabeculectomy, 186, 656 Trace element, 537, 546, 573, 611, 644, 655, 656 Tracer, 41, 79, 656 Trachea, 538, 539, 570, 595, 601, 623, 649, 654, 655, 656 Trachoma, 553, 656 Traction, 547, 656 Transcriptase, 595, 638, 652, 656, 664
Transcription Factors, 49, 62, 80, 89, 114, 194, 416, 423, 426, 439, 638, 656 Transdermal, 166, 391, 403, 418, 440, 656 Transduction, 20, 37, 78, 434, 540, 644, 656 Transfection, 49, 55, 536, 657 Transfer Factor, 587, 657 Transforming Growth Factor alpha, 657 Transforming Growth Factor beta, 657 Transforming Growth Factors, 50, 657 Transfusion, 235, 582, 657 Translation, 23, 80, 568, 657 Translational, 32, 90, 657 Translocation, 89, 439, 568, 657 Transmitter, 37, 120, 519, 531, 561, 569, 592, 601, 612, 651, 657, 659 Trauma, 108, 113, 198, 339, 340, 343, 364, 376, 446, 538, 609, 611, 636, 657 Treatment Failure, 304, 657 Triamcinolone Acetonide, 192, 402, 657 Trichomoniasis, 604, 657 Tricuspid Atresia, 552, 657 Tricyclic, 82, 658 Trigeminal, 37, 658 Trophic, 658 Trophoblast, 116, 118, 536, 658 Tropism, 658 Tropoelastin, 71, 658 Tryptophan, 76, 549, 643, 658 Tryptophan Hydroxylase, 76, 658 Tubercle, 613, 658 Tuberculin, 311, 658 Tuberculosis, 227, 254, 551, 599, 658 Tuberous Sclerosis, 174, 498, 658 Tumor Lysis Syndrome, 132, 658 Tumor marker, 535, 658 Tumor Necrosis Factor, 24, 224, 470, 658 Tumor suppressor gene, 658 Tumor-derived, 657, 658 Tumour, 166, 414, 476, 529, 575, 659 Type 2 diabetes, 79, 659 Tyramine, 535, 606, 659 Tyrosine, 20, 93, 434, 561, 659 U Ulcer, 365, 621, 659 Ulceration, 8, 45, 659 Ulcerative colitis, 4, 7, 31, 149, 155, 171, 214, 227, 365, 445, 469, 470, 471, 589, 659 Ultraviolet Therapy, 444, 659 Umbilical Arteries, 659 Umbilical Cord, 196, 546, 659 Umbilical cord blood, 196, 659 Uncompetitive, 241, 659
Index 695
Unconscious, 526, 557, 586, 659 Univalent, 584, 617, 659 Universal Precautions, 475, 659 Urea, 594, 651, 659 Uremia, 183, 594, 636, 659 Urethra, 9, 534, 620, 631, 659, 660 Uridine Diphosphate, 577, 660 Uridine Diphosphate Glucuronic Acid, 577, 660 Urinalysis, 148, 660 Urinary Plasminogen Activator, 655, 660 Urodynamics, 233, 446, 660 Urogenital, 79, 576, 660 Urologist, 107, 660 Uterine Contraction, 618, 660 Uvea, 565, 660 V Vaccination, 478, 660 Vaccine, 632, 658, 660 Vagina, 77, 79, 540, 545, 558, 559, 603, 637, 652, 660 Vaginal, 284, 354, 660 Vaginitis, 284, 540, 660 Vagus Nerve, 76, 660 Varicella, 132, 157, 478, 660 Vas Deferens, 116, 660 Vascular endothelial growth factor, 51, 71, 258, 660 Vascular Resistance, 71, 119, 661 Vasculitis, 205, 312, 626, 661 Vasectomy, 354, 661 Vasoactive, 661 Vasoconstriction, 368, 567, 661 Vasodilatation, 172, 568, 661 Vasodilation, 119, 526, 661 Vasodilator, 71, 119, 230, 537, 561, 583, 611, 661 Vasomotor, 568, 661 VE, 99, 304, 661 Vector, 46, 656, 661 Vegetative, 308, 547, 559, 661 Vein, 305, 311, 312, 316, 337, 338, 526, 591, 612, 620, 627, 640, 647, 650, 659, 661 Vena, 661 Venous, 129, 314, 536, 538, 632, 657, 661 Venous blood, 536, 538, 661 Venous Thrombosis, 129, 661 Ventilation, 33, 55, 184, 569, 661 Ventilator, 33, 130, 178, 230, 315, 601, 637, 661 Ventral, 407, 585, 613, 646, 647, 661
Ventricle, 368, 525, 531, 543, 552, 583, 613, 633, 652, 657, 661 Ventricular, 34, 134, 194, 552, 563, 584, 658, 661 Ventricular Dysfunction, 563, 661 Venules, 536, 540, 565, 604, 662 Verapamil, 148, 662 Vertebrae, 591, 646, 647, 662 Vertebral, 533, 625, 646, 662 Vertigo, 616, 662 Vesicular, 65, 91, 113, 531, 574, 579, 582, 604, 662 Vestibular, 223, 444, 445, 662 Vestibule, 548, 589, 642, 662 Vestibulocochlear Nerve, 532, 655, 662 Vestibulocochlear Nerve Diseases, 655, 662 Veterinary Medicine, 263, 493, 662 Villous, 546, 662 Vinyl Chloride, 662 Viral, 23, 24, 46, 55, 189, 274, 439, 471, 553, 564, 576, 614, 638, 656, 662, 663, 664 Viral Load, 662 Viral vector, 46, 662 Virilism, 323, 327, 355, 363, 585, 662 Virilization, 77, 441, 662 Virulence, 532, 656, 662 Virus Replication, 23, 663 Viscera, 645, 663 Visceral, 73, 95, 429, 532, 597, 622, 660, 663 Visceral Afferents, 532, 660, 663 Visceral fat, 429, 663 Viscosity, 402, 663 Visual Acuity, 45, 552, 663 Visual Cortex, 524, 663 Vitamin D, 29, 41, 259, 262, 267, 371, 376, 377, 398, 423, 466, 639, 663 Vitiligo, 632, 663 Vitreous Hemorrhage, 559, 663 Vitro, 27, 28, 29, 33, 50, 55, 60, 61, 63, 70, 71, 98, 99, 108, 109, 116, 117, 119, 145, 148, 149, 154, 157, 163, 173, 177, 183, 213, 217, 224, 259, 263, 273, 275, 299, 301, 302, 391, 404, 411, 421, 458, 543, 564, 581, 588, 627, 652, 655, 663 Vivo, 27, 28, 29, 30, 49, 55, 58, 60, 68, 76, 77, 84, 88, 98, 104, 108, 109, 116, 117, 118, 123, 124, 145, 185, 299, 301, 367, 391, 405, 412, 417, 425, 434, 458, 581, 588, 604, 617, 652, 654, 663 Voltage-gated, 22, 663 Vomeronasal Organ, 350, 614, 663
696 Steroids
Vulgaris, 390, 519, 663 W War, 580, 663 Weight Gain, 6, 78, 113, 663 Wheezing, 160, 368, 663 White blood cell, 305, 520, 527, 588, 596, 599, 600, 606, 607, 608, 611, 625, 664 Whooping Cough, 284, 622, 664 Windpipe, 539, 623, 654, 664 Womb, 637, 660, 664 Wound Healing, 245, 270, 543, 572, 590, 601, 664 X Xenobiotics, 80, 116, 131, 664 Xenograft, 108, 527, 664
Xerostomia, 594, 664 X-ray, 63, 64, 310, 311, 313, 314, 526, 537, 550, 573, 574, 593, 601, 607, 612, 634, 640, 647, 664 X-ray therapy, 593, 664 Y Yeasts, 540, 574, 591, 623, 664 Z Zalcitabine, 595, 664 Zona Fasciculata, 87, 117, 664 Zona Reticularis, 87, 117, 664 Zoster, 179, 665 Zygote, 550, 551, 665 Zymogen, 631, 665
Index 697
698 Steroids
Index 699
700 Steroids
