LOVASTATIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
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 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Lovastatin: 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: 0-597-84486-0 1. Lovastatin-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 lovastatin. 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 LOVASTATIN ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lovastatin...................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 18 The National Library of Medicine: PubMed ................................................................................ 19 CHAPTER 2. NUTRITION AND LOVASTATIN ................................................................................... 47 Overview...................................................................................................................................... 47 Finding Nutrition Studies on Lovastatin .................................................................................... 47 Federal Resources on Nutrition ................................................................................................... 49 Additional Web Resources ........................................................................................................... 49 CHAPTER 3. CLINICAL TRIALS AND LOVASTATIN.......................................................................... 53 Overview...................................................................................................................................... 53 Recent Trials on Lovastatin ......................................................................................................... 53 Keeping Current on Clinical Trials ............................................................................................. 55 CHAPTER 4. PATENTS ON LOVASTATIN .......................................................................................... 57 Overview...................................................................................................................................... 57 Patents on Lovastatin .................................................................................................................. 57 Patent Applications on Lovastatin............................................................................................... 76 Keeping Current .......................................................................................................................... 89 CHAPTER 5. PERIODICALS AND NEWS ON LOVASTATIN ................................................................ 91 Overview...................................................................................................................................... 91 News Services and Press Releases................................................................................................ 91 Academic Periodicals covering Lovastatin................................................................................... 94 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 97 Overview...................................................................................................................................... 97 U.S. Pharmacopeia....................................................................................................................... 97 Commercial Databases ................................................................................................................. 98 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 101 Overview.................................................................................................................................... 101 NIH Guidelines.......................................................................................................................... 101 NIH Databases........................................................................................................................... 103 Other Commercial Databases..................................................................................................... 105 APPENDIX B. PATIENT RESOURCES ............................................................................................... 107 Overview.................................................................................................................................... 107 Patient Guideline Sources.......................................................................................................... 107 Finding Associations.................................................................................................................. 111 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 113 Overview.................................................................................................................................... 113 Preparation................................................................................................................................. 113 Finding a Local Medical Library................................................................................................ 113 Medical Libraries in the U.S. and Canada ................................................................................. 113 ONLINE GLOSSARIES................................................................................................................ 119 Online Dictionary Directories ................................................................................................... 119 LOVASTATIN DICTIONARY.................................................................................................... 121 INDEX .............................................................................................................................................. 175
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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 lovastatin 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 lovastatin, 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 lovastatin, 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 lovastatin. 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 lovastatin, 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 lovastatin. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON LOVASTATIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lovastatin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and lovastatin, 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 “lovastatin” (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: •
Why is Cholesterol So Important? Source: Diabetes Self-Management. 11(3): 48, 50-53. May-June 1994. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: In this article, the author provides basic information about cholesterol for people with diabetes. Topics include the differences between saturated and unsaturated fat, the causes of elevated fat and cholesterol levels in the blood, the metabolism of cholesterol, how atherosclerosis develops, where dietary fats and cholesterol come from, and how to lower high cholesterol levels. The author concludes with a review of the cholesterol-lowering medications that are currently available, including colestipol, probucol, lovastatin, pravastatin, and simvastatin, nicotinic acid, and gemfibrozil.
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Decreased Prevalence of Alzheimer Disease Associated With 3- Hydroxy-3Methyglutaryl Coenzyme A Reductase Inhibitors Source: Archives of Neurology. 57: 1439-1443. October 2000. Summary: This article examines the effects of statins on the prevalence of Alzheimer's disease (AD). Statins are a class of medications which reduce the level of plasma cholesterol by inhibiting the enzyme 3- hydroxy-3-methylglutaryl coenzyme A reductase. Data were obtained from the records of three hospitals for the period October 1996 through August 1998. The prevalence of probable AD was determined for three groups of patients over age 60 years: the entire population, patients receiving statins, and patients receiving medications other than statins that are used to treat hypertension or cardiovascular disease. The prevalence of AD in the group taking lovastatin or pravastatin was 60 percent to 73 percent lower than in the total population or in the group taking other medications commonly used in the treatment of hypertension or cardiovascular disease. Although causative mechanisms cannot be inferred, results indicate that the use of statins is associated with a lower prevalence of AD. 1 figure, 1 table, 17 references.
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Hyperlipidemia Therapy in Diabetes Source: Diabetes Educator. 18(2): 105-106, 108-109. March-April 1992. Summary: This article reviews the importance of maintaining control of serum lipid levels in people with diabetes to reduce risks for coronary artery disease. Topics include lipid metabolism; lipid handling in diabetes; and therapy for hyperlipidemia, including diet, exercise, and drug agents such as bile acid sequestrants, niacin, gemfibrozil, and clofibrate, lovastatin, thyroxine, and probucol. The author focuses on the importance of patient education for better patient compliance and better control of both diabetes and lipids. 2 tables. 1 reference.
Federally Funded Research on Lovastatin The U.S. Government supports a variety of research studies relating to lovastatin. 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. 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 lovastatin. 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 lovastatin. The following is typical of the type of information found when searching the CRISP database for lovastatin:
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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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Project Title: CALGB INSTITUTIONAL GRANT Principal Investigator & Institution: Clamon, Gerald H.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-APR-1988; Project End 31-MAR-2009 Summary: (provided by applicant): The University of Iowa has been a member of CALGB since 1986. Accrual at the main member hospital is approximately 100 patients per year and approximately 20 more patients are accrued at two affiliates. Over the past 5 years, we have authored or co-chaired studies in non-small cell lung cancer, in chemoprevention of lung cancer, in experimental therapeutics for 506U78, and for omega-3 fatty acids in cancer cachexia. Administratively, Dr. Gerald Clamon has been vice chair of the Membership Committee and Dr. Raymond Hohl has been vice chair of the Institutional Performance Evaluation Committee (IPEC). In addition, Dr. Clamon is on the Respiratory Committee and is the liaison to the Cancer Control and Health Outcomes Committee, Dr. Hohl is on the Leukemia Committee and is the liaison to the Pharmacology and Experimental Therapeutics (PET) Committee, Dr. Brian Link is on the Lymphoma Committee, and Dr. Badrinath Konety is on the GU Committee. Dr. Nancy Rosenthal is reviewing slides for the Hematopathology Committee for a lymphoma trial, Dr. Shivanand Patel reviews cytogenetics for the Leukemia Committee, and Dr. Michael Vannier is serving on a new committee to evaluate new technologies in the imaging of tumors. New translational research at the University of Iowa has lead to the development of two new promising anti-cancer therapies. The HU 1D10 antibody developed in the laboratory of Dr. George Weiner at the University of Iowa has completed Phase I trials at the University of Iowa and demonstrated activity against lymphoma. The CpG oligodeoxynucleotide developed at the University of Iowa in the lab or Dr. Arthur Krieg is now completing Phase I trials at the University of Iowa. A pilot study of Pneumovax plus GM-CSF is being completed at the University of Iowa. This should lead to a phase III trial within CALGB and potentially improve success with vaccinations of the immune suppressed cancer patient. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CASE CONTROL STUDY OF STATIN USE AND LARGE BOWEL CANCER Principal Investigator & Institution: Coogan, Patrica F.; Epidemiology and Biostatistics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 18-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract): Cancer of the large bowel is a leading cause of cancer morbidity and mortality in the United States. Our previous epidemiologic studies played a key role in documenting an inverse association between the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) and the incidence of large bowel cancer. Those studies were inspired by laboratory data suggesting that NSAIDs may reduce colon carcinogenesis. Now a growing body of laboratory data indicates that the commonly used, relatively new class of cholesterollowering drugs, the "statins" may have a similar chemopreventive potential: statins inhibit the growth of colon cancer cells in vitro and in vivo. There is also some evidence that statins may enhance the chemopreventive effect of NSAIDS. The statins (e.g., lovastatin, simvastatin) were first marketed in 1987, and are now among the most commonly prescribed drugs in the United States. At this time there is little epidemiologic data concerning their potential protective effect against large bowel cancer. Two randomized trials of statin use as preventives of coronary heart disease had
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nonsignificant deficits of large bowel cancer in the treated groups. We propose to conduct a population-based case-control study in Massachusetts of the relation of statin use to the risk of large bowel cancer. We will identify 2050 incident cases aged 50-74 through participating hospitals and 2050 age, sex, and precinct matched community controls from Massachusetts town lists. Cases and controls will be interviewed to obtain information on demographic factors, risk factors for large bowel cancer, detailed histories of statin and NSAID use, and data useful for addressing potential biases. The study is large enough to assess the influence of characteristics of statin use (timing, duration, dose) on the risk of large bowel cancer and to assess consistency of findings across subgroups of age, sex, and cancer site. The joint effect of statins and NSAIDs will also be assessed. The proposed study will provide informative epidemiologic data on a potential chemopreventive of large bowel cancer. Because the incidence of the disease and prevalence of statin use by U.S. men and women are high, an inverse association would be of considerable public health importance. Moreover, it would shed light on a mechanism of colon carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL CYCLE BLOCK BY HMG CO-A REDUCTASE INHIBITORS Principal Investigator & Institution: Ukomadu, Chinweike; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This application is intended to provide outstanding mentorship and a supportive laboratory environment to foster the development of Chinweike Ukomadu, M.D., Ph.D., towards a career as an independent scientist. The candidate has completed graduate studies and published several papers in the field of ion channel physiology. Following clinical training in internal medicine and gastroenterology he returned to the laboratory to study mechanisms of cell cycle regulation. The proposed research will be carried out in the laboratory of Anindya Dutta, M.D., Ph.D., an internationally recognized investigator in the area of cell cycle regulation. Dr. Dutta's record in mentoring numerous junior scientists as they transitioned to careers as principal investigators provides an ideal setting for implementation of the goals of this proposal. Dr. Dutta's laboratory has extensive expertise in cell biological, biochemical, and genetic methodologies related to cell cycle studies. Seminars, conferences, and collegial interactions within the Departments of Pathology and Internal Medicine at Brigham and Women's Hospital will offer additional opportunity for scientific and career development. This proposal outlines detailed studies aimed at further understanding the regulation of cyclin dependent kinase 2 (Cdk2), a key enzyme required for progression through the cell cycle. The studies will be carried out using established cancer cell lines. In preliminary studies, mevastatin, a cholesterol lowering agent, inhibited Cdk2 by preventing activating phosphorylation. The specific aims are: 1) to determine the molecular mechanism by which mevastatin inhibits the activation of Cdk2; 2) to show that cyclin H:cdk7, which has been felt to be essential for activation of Cdk2, is not required in some cancer cell lines; and 3) to elucidate the events underlying the inability of p21 to inhibit Cdk2 in some cancer cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMOPREVENTION IN AN INDUCIBLE MOUSE MELANOMA MODEL Principal Investigator & Institution: Spanjaard, Remco A.; Associate Professor; Otolaryn & Head & Neck Surgery; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The number of cases of malignant cutaneous melanoma has been rising at an alarming rate over the last decades, at about 4% per year, and it has been estimated that up to 1 in 80 Americans will develop melanoma. Despite years of research, there are no viable treatment modalities for advanced melanoma, and mortality rates remain exceptionally high. This saddening fact emphasizes the urgent need for new effective drugs, not only to treat existing tumors, but also to inhibit occurrence of second primary cancers after convential treatment modalities, or prevent further transformation of premalignant cells in high-risk patients. This application aims to address these issues by assessing the chemopreventive activity of a promising selection of drugs in a novel, inducible murine melanoma model. This uniquely suitable model is the only one to allow synchronization of the onset of development of cutaneous melanoma on a genetic background, which accurately mimics that of human disease. By adding doxycyclin (Dox) to the drinking water, expression of H-RASV12G is induced in melanocytes on a p16INK4A-ARF null background. This cooperativity then results in development of largely non-metastatic, cutaneous melanomas in 25% of mice with an average latency of 60 26 days. The mouse model itself has already been thoroughly analyzed in terms of tumor pathology, which closely resembles that of human disease, and the essential role for H-Ras in maintaining tumor growth. However, these mice have never been used to develop new chemoprevention protocols. We will test the efficacy of the following drugs: suberohydroxamic acid (SHA), celecoxib, retinoic acid (RA) and lovastatin. These drugs were selected because they i) are non-toxic (except for RA, but 13-cisRA provides a less toxic clinical alternative), ii) are widely used already, iii) affect different biochemical pathways, iv) have shown promise as chemopreventive agents in other studies, and v) have shown potential to enhance each other's activity when combined. Our working hypothesis is that these drugs will inhibit tumor growth to some degree, but that the combination of at least some of these drugs will inhibit proliferation of premalignant melanoma cells to a much larger extent than any drug alone can achieve, without significantly increasing toxicity. We propose to induce 4-week old animals drugs, and determine chemopreventive antitumor efficacy by monitoring size, number and location of skin tumors. Specific Aim I proposes to establish an optimal chemoprevention drug protocol to suppress tumor development. Specific Aim II proposes to establish expression of key cell cycle regulatory genes in control, drug-responsive and nonresponsive transgenic tumors to determine whether expression is associated with tumor growth and responsiveness to therapy. The results of these experiments in this inducible melanoma model will allow us to assess whether our protocol should be considered for use in phase I trials in high risk patients, which is the long term goal of this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMOPREVENTION IN MICE AFTER TOBACCO SMOKE EXPOSURE Principal Investigator & Institution: Witschi, Hanspeter R.; Professor, Associate Director; None; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): In former smokers, "suppressing" chemopreventive agents, i.e. agents which have chemopreventive activity when given after the carcinogen, would appear to most useful. We have established that strain A mice exposed for five months to tobacco smoke and then kept for another four months in air develop significantly more lung tumors than do animals kept in air. We further have shown that a diet containing a mixture of myoinositol (10 g/kg diet) and dexamethasone (0.5 mg/kg diet) successfully prevents lung tumor development in mice exposed to tobacco smoke. The chemopreventive regimen is even effective when the animals are fed the myoinositol-dexamethasone diet once they have been removed from the smoke atmosphere. Thus we have an animal model that mimics "former smokers" and where other suppressing chemopreventive agents or treatment modes may be evaluated. Since myoinositol is a food constituent with no known toxicity, it will be explored whether myoinositol alone, fed in the diet, will give chemoprevention to mice that have "quit" smoking. In a second series of experiments we will examine whether the topical administration to the tissues of the respiratory tract of other suppressing agents (budesonide- epigallocatechin gallate (EGCG), isotretinoin, or lovastatin) may increase their efficacy while at the same time reducing their potential systemic toxicity in mice previously exposed to tobacco smoke. Eventually, these preclinical studies in an animal model of "former smokers" will help to evaluate the potential usefulness and also possible dosage regimens of chemopreventive agents characterized by their suppressing action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHINESE RED YEAST RICE COMPARISON TO LOVASTATIN Principal Investigator & Institution: Heber, David; Professor/Chief; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: This project will evaluate the effect, on cholesterol biosynthesis and atherosclerotic lesion formation, of a mixture of monacolins isolated from a yeast fermented rice compared to Lovastatin. This will be accomplished by measuring upregulation of HMG-COA gene transcription in HEPG2 cell constructs containing a luciferase reporter gene. A second end point will be the formation of atherosclerotic lesions and measuring blood cholesterol levels in ApoE knockout mice. The final study will assay the bioavailability of the mixture of monacolins from red yeast rice and of pure Lovastatin in human volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL TRIALS COMPONENT Principal Investigator & Institution: Aranow, Cynthia; Albert Einstein College of Med Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Dr. Cynthia Aranow will direct the clinical trials initiative in the Center. Investigators in the divisions of Rheumatology, Endocrinology, Gastroenterology and Hematology will participate in performing clinical trials in autoimmune disease. There is a General Clinical Research Center (GCRC) to support these studies. The GCRC includes an administrative, nursing and biostatistical infrastructure, as well as a laboratory for several standard procedures. Two clinical trials are proposed: one to explore the use of statins in rheumatoid arthritis and a second to test whether DNase I reduces chromatin and DNA reactivity in systemic lupus. The reagents needed for these
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trials are readily available. The clinical trials initiative will be guided by an internal advisory committee consisting of clinical and translational researchers, most of whom are also practicing clinicians. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTINUOUS DOT IMAGING OF HEMODYNAMICS DURING STROKE Principal Investigator & Institution: Culver, Joseph P.; Instructor - Assistant Physicist; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 03-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Continuous DOT Imaging of Hemodynamics During Stroke" is submitted in response to the NINDS program announcement for Mentored Quantitative Research Career Awards (K25). The candidate seeks to gain training in the neurobiology of Stroke and to advance the methods of Diffuse Optical Tomography (DOT) for application in stroke physiology. Stroke is both caused by, and induces deranged hemodynamics. It is therefore not surprising that the hemodynamic status of ischemic tissue contains vital and abundant information about microvasculature integrity, deficient cerebral metabolism, and abnormal neuronal activity. Diffuse optical imaging of the brain is an attractive approach for evaluating stroke physiology. The method provides complementary hemodynamic and metabolic imaging contrasts to those of Magnetic Resonance Imaging (MRI) with a unique potential for continuous non-invasive bedside imaging in humans. However quantitative spatial-temporal, comparative studies with established medical imaging techniques are lacking. In addition, experience with diffuse optical signatures of stroke pathophysiology is limited, and mostly involves non-imaging measures. The goal of this work is to establish new DOT hemodynamic and metabolic methodologies through concurrent DOT-N4RI animal (rat) studies, and apply the methods to examine the spatial-temporal evolution of reperfusion and hemorrhagic transformation with thrombolytics. The new DOT techniques are based on NEU guided Monte-Carlo diffuse light modeling, and hybrid time resolved and continuous-wave light measurements. Methods for quantifying and imaging cerebral blood volume (CBV), cerebral blood flow (CBF), and indexes of cerebral oxygen metabolism (CMRO) will be validated through global and focal programmed modulations of cerebral vasculature and physiology. Subsequent studies will explore DOT markers relevant to focal ischemia, thrombolytics, and hemorrhage due to reperfusion. Through the training that this award provides the applicant will gain sufficient background in the neuroscience and cerebral ischemia to lead cross-disciplinary research projects that aim to further the knowledge of stroke physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COSTIMULATORY BLOCKADE AND STATINS FOR MURINE SLE Principal Investigator & Institution: Davidson, Anne; Associate Professor; Albert Einstein College of Med Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Statins, inhibitors of HMG CoA reductase, a key enzyme in the cholesterol synthetic pathway, effectively prevent both primary and secondary coronary vascular disease. The beneficial effect of the statins is not all due to their cholesterol lowering function. Recently multiple immunosuppressive effects of statins have been demonstrated both in models of inflammation and of vascular injury. Most of these
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effects are due to decreased synthesis of mevalonate-derived intermediates that are required for full activation of small GTP binding proteins such as Rho and Ras. Thus there has been increasing interest in possible clinical utility of statins for autoimmune diseases. Our laboratory is interested in developing therapeutic combination regimens of drugs that act on different pathways of immune activation and target organ damage. We have previously focused on the mechanism of action of biologic agents that inhibit costimulatory pathways of B and T cell activation. In this proposal we will ask whether treatment with statins will synergize with costimulatory blockade for the treatment of two different manifestations of SLE; inflammatory renal disease and non-inflammatory vasculopathy. The initiation of both these SLE manifestations is immune mediated but the tissue response to autoantibody-mediated damage is different in each case. Both however may be susceptible to the beneficial effects of statins. In aim 1 we will determine the effect of statins in SLE nephritis. We will ask whether statins will synergize with CTLA4Ig in prevention of SLE nephritis and whether they will help maintain remission of nephritis after treatment with a short course of CTLA4Ig and cyclophosphamide. Effects of therapy on immunologic parameters and effector responses in the kidney will be evaluated by a series of assays that are well established in the laboratory. In aim 2 we will utilize a murine model of vasculopathy induced by anti-phospholipid antibodies and ask whether statins, with or without CTLA4Ig, will prevent disease intitiation or progression. In aim 3 we will determine whether monocytes and dendritic cells from patients with inactive SLE are susceptible to the known immunoregulatory effects of statins and determine which statin is most potent. These studies will gather information that may support a clinical trial of statins in SLE patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINES IN GLIAL CELLS AND EAE BRAIN Principal Investigator & Institution: Singh, Inderjit; Scientific Director; Pediatrics; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: The presence of proinflammatory cytokines and induction of inducible nitric oxide synthase (iNOS) in brain lesions of patients with multiple sclerosis (MS) provided evidence that NO/ONOO' along with free radicals of oxygen (02-) play an important role in the pathophysiology of MS. Studies from our laboratory have shown that cAMP inhibitors of protein phosphatases 1/2 A regulate the production of NO and induction of iNOS in astrocytes and macrophages by different mechanisms. NO alters the cellular redox by altering the expression of antioxidant enzymes. We have also shown that antioxidants (N-acetyl cysteine) and mevalonate inhibitors (lovastatin and sodium phenylacetate) block the induction of proinflammatory cytokines and that of iNOS and the production of NO in activated cultured astrocytes, macrophages and microglia. The objective of this proposal is to decipher the mechanism of the induction or regulation of iNOS in astrocytes and macrophages by PKA and protein phosphatases 1/2 A and the role of iNOS in the disease process of experimental allergic encephalitis (EAE), an animal model of MS. Achievement of these goals will be facilitated by understanding the molecular mechanism of activation of NFkB in the differential induction of iNOS by PKA and protein phosphatases 1/2 A in astrocytes and macrophages. Studies are proposed to identify the protein phosphatase (protein phosphatase I or protein phosphatase 2A) that is responsible for the induction of proinflammatory cytokines NFkB and activation of iNOS in astrocytes and macrophages. The possible role of NO/ONOO' in the pathophysiology of EAE will be investigated by using mice models
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which lack iNOS (iNOS knock out) and those which express increased levels of iNOS. We also propose to test the possible therapeutic effect of antioxidants drugs (Nacetylcysteine) and mevalonate inhibitors (lovastatin and sodium phenylacetate) in halting/slowing the progression of the disease process in EAE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF STATINS ON HIV-1 BIOLOGY Principal Investigator & Institution: Fletcher, Craig A.; Comparative Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Dr. Craig Fletcher, a veterinarian, is in a structured postdoctoral fellowship program in Laboratory Animal Medicine and will continue to expand upon his scientific skills through unique integration of clinical training in comparative medicine and formal doctoral training. The purpose of this Mentored Clinical Scientist Development Award is to support a research program in cellular immunology and retroviral pathogenesis, which will culminate in both the Ph.D. degree and the opportunity for continued research experience. Dr. Fletcher's long-term goal is to become a principal investigator employing animal models to investigate the pathogenesis and therapy of HIV. The principal investigator's scientific training will be conducted in the Leukocyte Immunochemistry Laboratory at Johns Hopkins University, under the guidance of the sponsor Dr. James E. K. Hildreth. The candidate's training plan includes laboratory and didactic training in contemporary molecular techniques and research methods, applied to an animal model of AIDS. Preliminary work conducted by the principal investigator in the Hildreth's laboratory suggests that statins (lovastatin) inhibit HIV-1 and SIV infection and replication in vitro. The study design is aimed at understanding the mechanisms by which integrins and lipid rafts play a role in HIV and SIV biology in vitro. The three specific aims to be addressed are: (1) to determine if statins affect lipid raft formation thus alter the incorporation of integrins (and other cellular proteins) into HIV-1 virions; (2) to determine the impact of statin modulation of integrin and chemokine receptor function on HIV budding, entry, and virus-induced chemotaxis in vitro; (3) to determine if statins inhibit the spread of HIV and SIV in PBMC cultures by inducing apoptosis. Statins are among the most powerful cholesterol lowering drugs available and are widely prescribed around the world. Dyslipidemia and hypercholesteremia are prevalent conditions in patients with HIV infection on anti-retroviral therapy. In addition to this drug family's effect on cholesterol synthesis, investigators have recently found that statins directly inhibit the major a2 integrin, LFA-1. Given this dual effect of statins and the important role of LFA-1 and lipid rafts in the biology of HIV-1, these compounds represent a potentially important therapeutic and investigative tool for AIDS. The Department of Comparative Medicine of the Johns Hopkins University provides an ideal setting for training veterinarianscientists and maximizes the potential for the principal investigator to establish a strong research foundation and develop into an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF SBE ON MALE MONKEYS Principal Investigator & Institution: Adams, Michael R.; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002
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Summary: (Adapted from Applicant's Abstract) There is no means of coronary heart disease prevention for men that combines the qualities of safety, effectiveness, wide acceptability and low cost. While the "statin" group of compounds, e.g., lovastatin, pravastatin, is effective in preventing coronary events, there are issues regarding side effects, compliance and cost that limit their use. Soy phytoestrogens may represent an alternative to pharmacologic means of coronary heart disease prevention. There is limited evidence indicating that soy consumption inhibits atherogenesis and has favorable effects on coronary vascular reactivity while having favorable or neutral effects on other organ systems. The major objective of Project 2 is to assess the usefulness of soy phytoestrogens in primary cardioprotection of adult male monkeys. The study will address directly whether long-term soy consumption is without adverse effects on the reproductive system, cognition, social or sexual behavior and function and determine if it has favorable effects on the prostate gland. Ninety cynomolgus monkeys will be randomized to three treatment groups: 1) placebo atherogenic diet (n=30), 2) low phytoestrogen atherogenic diet (58 mg/1800 Cal) (n=30) and 3) high phytoestrogen atherogenic diet (120 mg/1800 Cal) (n=30). Diets are identical in atherogenicity and nutritional content; they differ only in phytoestrogen content. During a 36 month treatment period, assessments will be made of plasma lipoproteins, blood pressure, arterial vasomotor function, sociosexual function, testicular endocrine and spermatogenic function, and cognitive function. Postmortem assessments will be made of atherosclerosis extent and arterial expression of estrogen receptors (alpha and beta). In addition, immunohistochemical and histomorphometric markers of prostatic hyperplasia and neoplasia will be studied as will histomorphometric markers of mammary gland hyperplasia and neoplasia. Spermatogenesis will also be assessed. Finally, assessments will be made of behavior-relevant immunohistochemical markers of estrogenic stimulation in the central nervous system. Since the body of data that exists currently regarding the effects of soy on the cardiovascular, reproductive, and central nervous systems is quite limited, this study represents a necessary step in elucidating the potential for a favorable public health impact of widespread soy consumption by men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLOBOID CELL LEUKODYSTROPHY Principal Investigator & Institution: Singh, Avtar K.; Pathology and Lab Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 12-APR-2001; Project End 31-MAR-2006 Summary: (Verbatim from the Applicant's Abstract) Globoid cell leukocystorophy (Krabbe's Disease) is an autosomal metqabolic disordear of beta-galactocerebrosidase deficiency with progressive pathognomonic accumulation of psychosine (galactosylsphingosine) which subsequently becomes a neuroinflammatory disease resulting in demyelination, olidogendrocyte loss and death. The objectives of the proposed studies are to elucidate the possible role of psychosine in neuroinflammatory response and in the mechanism of oligodendrocyte loss by using twitcher mice, a murine model of globoid cell leukodystrophy (GLD). Studies from our laboratory have demonstrated the psychosine potentiates the cytokine-induced induction of iNOS and also the psychosine when incubated with C6 glial cells in culture, induces apoptotic cell loss. Achievement of these goals will be facilitated by understanding the molecular mechanism of induction of inducible nitric oxide synthase (iNOS) and inflammatory cytokines (e.g. TNFalpha and IL-6) and psychosine-induced apoptotic loss of oligodendrocytes. Studies are also proposed to investigate the psychosine-induced
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electrophysiological alterations in brain cells/brain slices form twitcher mice. We also propose to test the efficacy of antioxidants (N-acetyl cysteine, alpha-lipoic acid) and the compounds that are known to block the induction of inflammatory cytokines (lovastatin, sodium phenylacetate) for halting/delaying the disease process in twitcher mice. The proposed studies will provide a better understanding of the disease process in GLD/twitcher mice and the demonstration of beneficial effects of the drugs in twitcher mice) may help in the identification of an ideal candidate drug for subsequent use in clinical trials involving GLD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HMG COA REDUCTASE AND COX2 INHIBITORS IN COLON CANCER Principal Investigator & Institution: Rao, Chinthalapally V.; Associate Chief/ Professor; Institute for Cancer Prevention 1 Dana Rd Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The overall objective of this proposal is to determine the chemopreventive efficacy of a combination of lovastatin (3-hydroxy-3methylglutaryl CoA reductase (HMG-R) inhibitor and celecoxib (COX-2-selective inhibitor) against colon cancer and to gain an understanding of the mechanism(s) of tumor inhibition by these agents. Colorectal cancer is one of the most common human malignancies in the United States, anticipated to account for 137,000 new cases and about 56,000 deaths in the year 2001. Developing chemopreventive agent(s) that aim to suppress tumor cell growth, but not normal cell growth, by targeting specific genes/factors that are responsible for tumor growth provides a rational approach. Our studies and those of others indicate that COX-2 and HMG-R activities were upregulated several-fold in colon tumors compared to normal mucosa and, importantly, the metabolites/molecules derived from these enzymes play a pivotal role in modulation of apoptosis and proliferation. Recent evidence from clinical trials, and in vivo and in vitro laboratory studies suggest that application of a combination of HMG-R inhibitors (cholesterol-lowering drugs) and COX-inhibitors (nonsteroidal antiinflammatory drugs) produces synergistic colon cancer-inhibiting effects. Thus, it is important to systematically develop HMG-R inhibitors and their combination with COX-2 inhibitors for colon cancer prevention and delineate the specific mechanisms that lead to modulation of apoptosis and proliferation by these agents. Specifically, we will examine 1) the chemopreventive efficacy of lovastatin on azoxymethane (AOM)induced colon carcinogenesis in rats (maximum tolerated dose selection; dose-response effects; and effectiveness during promotion/progression stages, 2) study the synergistic effects of lovastatin and celecoxib on AOM-induced colon carcinogenesis and assess effectiveness of these agents in combination on the promotion/progression stages, and 3) elucidate mechanisms by determining the effect(s) of lovastatin with or without combination of celecoxib on HMG-CoA reductase, FPTase, GGPTase, p53, p21CIP/WAF1, caspase-3 &- 6, Bax, Bcl-2, Fas and lamin B, COX-2, PPAR-y, p53, and prostaglandins levels. Finally, we will study the effects of these agents on cell proliferation, and apoptosis during different stages of colon carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LOVASTATIN THERAPY FOR ADRENOLEUKODYSTROPHY Principal Investigator & Institution: Pai, Shashidhar G.; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425
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Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA CHEMOPREVENTION Principal Investigator & Institution: Dellavalle, Robert P.; Dermatology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The incidence of cutaneous malignant melanoma is rising faster than any other cancer in the US. 1 in 74 Americans will develop melanoma, more than 45,000 cases will be diagnosed, and more than 7,500 Americans will die from melanoma this year. Effective prevention of melanoma will not only save lives, but will also decrease the estimated one billion dollars spent annually treating melanoma in the US. There is currently no recognized chemoprevention for melanoma. Two large, randomized, placebo-controlled clinical trials, the VA-HIT Study utilizing gemfibrozil, and the AFCAPS Study utilizing lovastatin, have each reported an association of lipidlowering medication therapy with statistically significant lower melanoma incidence rates. Lovastatin inhibits melanoma cell growth in tissue culture, and mice Jed lovastatin develop lower lung metastases following tail vein injection with mouse B16 melanoma cells. More recently low concentrations of atorvastatin have been reported to specifically induce apoptosis and inhibit migration of human A375 melanoma cells but not cultured melanocytes. To investigate the unconventional hypothesis that lipidlowering medications might prevent melanoma, a case-control study will be conducted utilizing Veterans Administration (VA) databases to answer the following question: Do persons who have developed cutaneous malignant melanoma have a history of less lipid-lowering medication exposure than persons who are spared the disease? The answer to this question will help determine whether more expensive and labor intensive randomized prospective clinical trials of potentially teratogenic lipid-lowering medications should be initiated in persons at high risk of developing melanoma. Robert Dellavalle, MD, Ph.D., is an Assistant Professor of Dermatology at the University of Colorado Health Sciences Center and a staff dermatologist at the Denver VA medical center He is committed to a career in academic dermatology and public health. His current career goals are completing a Masters of Science in Public Health and becoming an independent researcher in skin cancer prevention and control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MECHANISM OF HMG COA REDUCTASE Principal Investigator & Institution: Stauffacher, Cynthia V.; Professor; Biological Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-MAR-2004 Summary: Our laboratory is pursuing a multi-faceted research projects to understand the molecular mechanism of the enzyme 3-hydroxyl-3- methylglutaryl co-enzyme A (HMG-CoA) reductase by a combination of biophysical and X-ray crystallographic methods. From the 2.8A structure of the Pseudomonas mevalonii enzyme and a number of binary and ternary complexes with substrates, we have outlined a catalytic mechanism which we believe applies to all members of this class of enzymes. We now propose to investigate the mechanistic proposal with a combination of crystallographic and kinetic measures, with the goal of trapping structurally significant intermediates in the catalytic reaction, and will extend these studies to the HMG-CoA reductases of a
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number of different species. We will also begin to investigate the structural basis of the modulation of activity in HMG-CoA reductase by reversible phosphorylation in the mammalian enzymes, while attempting to crystallize one of the mammalian reductases. Finally, we intend to begin investigations of species specific differences in the active sites of HMG-CoA reductases from bacteria, archeabacter and eukaryotes which may lead to the development of species-selective inhibitors for this enzyme. The specific aims of this proposal are to: 1) Complete the crystallographic studies of the enzyme-substrate complexes involved in the molecular mechanism of Pseudomonas mevalonii HMG-CoA reductase. 2) Use steady-state and fast reaction kinetics with possible suicide inhibitors to identify and characterize intermediates produced during the Pseudomonas HMGCoA reductase reaction which can be examined by X- ray crystallographic techniques, and to extend these studies to the Sulfolobus and Syrian hamster enzymes. 3) Investigate the basis of phosphorylation control of HMG-CoA reductase with X-ray crystallographic studies of an engineered Pseudomonas enzyme. 4) Express, purify, characterize and crystallize representative HMG-CoA reductases from the Class I and Class II enzymes in order to examine how the observed differences in their biological and biochemical properties are expressed in their structures. 5) Use the crystallographic structures for these enzymes to identify differences that could be exploited to design species/specific inhibitors for HMG-CoA reductase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL OSTEOINDUCTIVE PROTEIN SYNTHESIZING IMPLANT SYSTEM Principal Investigator & Institution: Whang, Kyumin; Assistant Professor; Restorative Dentistry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant) Therapies to aid healing of bone wounds and defects are major needs. Recently, small molecules that can induce expression of the bone morphogenetic protein (BMP)-2 gene in osteoblasts and bone marrow (BM) cells have been identified, such as the statins (e.g. lovastatin, simvastatin). However, their use in bone formation is limited due to a lack of suitable delivery vehicles. The long-range goal of this work is to develop optimized delivery devices for tissue engineering. The objective for this application is to determine the effect of different strategies for delivering statins from resorbable polymer scaffolds on bone regeneration in vitro and in vivo: diffusion-controlled delivery of statins, the slow degradation-controlled delivery of OG-PLG, and the continued in vivo stimulation of seeded BM cells to produce native BMP-2 using a novel Osteoinductive Protein Synthesizing Implant System (OPSIS). We have developed the strategy of an OPSIS to combat the problem of poor delivery. This system consists of OG-PLG fabricated into a three-dimensional scaffold using the emulsion freeze-drying (EFD) process, and seeded with BM cells. OGPLG is synthesized by grafting simvastatin to the end of biodegradable poly[lactide-coglycolide] (PLG) polymers. Preliminary in vitro studies showed that constant delivery of small amounts of lovastatin (2.5 ug/day) from EFD scaffolds enhanced the efficacy of the drug to form new bone by approximately two orders of magnitude over local subcutaneous injections. However, no bone was found inside the scaffolds because lovastatin is not chemotactic and bone cells were not recruited into the scaffold, and localized cytotoxicity was observed at high doses. Thus, the concept of the OPSIS was developed to continually stimulate BM cells seeded in OG-PLG scaffolds to synthesize native BMP-2 in vivo and stimulate both seeded BM cells and surrounding host cells to
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form bone. OG-PLG synthesis was confirmed using contact angle measurements, Attenuated Total Reflectance-FTIR and UV-Vis spectroscopy. The hypothesis to be tested is that osteoinduction is enhanced by slow degradation-controlled release of OGPLG for interaction with seeded BM cells to induce synthesis of BMP-2 in the OPSIS. Two specific aims are proposed: 1) to determine the effects of binding statin onto PLG on osteoinduction in vitro and 2) to determine the effects of binding statin onto PLG and BM cell transnlantation on osteoinduction in vivo. Results will bridge the gap between basic research and clinical application because statins are as potent as the most powerful bone growth factors not yet FDA approved for clinical use and substantially (16,000fold) cheaper to synthesize, and with an optimized delivery system even large, critical or nonunion defects will be treated effectively and efficiently. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPEN LABEL TRIAL OF NICOSTATIN (NIACIN /LOVASTATIN) Principal Investigator & Institution: Crouse, John R.; Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REACTIVE NITROGEN & CEREBRAL ISCHEMIC INJURY Principal Investigator & Institution: Khan, Mush; Pediatrics; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 15-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) Acute ischemic stroke is a major cause of disability especially among the elderly and is the third leading cause of death. Reactive nitrogen species (NO and ONOO') are being increasingly implicated in the pathophysiology of cerebral ischemia-reperfusion injury. Since inducible nitric oxide synthase (iNOS) is a high output enzyme and it is active for days when induced, we hypothesized that NO produced by iNOS is an important factor in the pathophysiology of cerebral ischemia-reperfusion injury. We have identified a number of compounds (Nacetylcysteine, lovastatin, mevastatin and sodium phenylacetic acid) which will inhibit the induction of iNOS and proinflammatory cytokines in brain cells in culture. The proposed studies will test the therapeutic potential of these drugs against cerebral ischemia-reperfusion injury. The first and second specific aims are designed to investigate whether N-acetylcysteine, alpha-lipoic acid and/or lovastatin will block/down regulated the induction of proinflammatory cytokines and iNOS in brain exposed to ischemia/reperfusion injury. The third specific aims is designed to investigate whether N-acetylcysteine or lipoic acid and/or lovastatin will block/down regulate the induction of delayed cell loss by apoptosis in brain exposed to ischemia/reperfusion injury. From these studies we will seek to answer the following questions: 1) Does treatment with the drugs prevent the neuronal injury given prior to the onset of ischemia? 2) Does treatment with the drugs prevent the neuronal injury by altering the course of the disease when given after the ischemic insult. These are relatively nontoxic compounds and are presently being prescribed for human consumption in other diseases. Therefore, demonstration of beneficial effects of these drugs in an animal model of cerebral ischemia-reperfusion injury will help identify the ideal candidates for subsequent use in clinical trials involving cerebral ischemia and stroke.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SHEAR STRESS ACTIVTION OF ENDOTHELIAL MEMBRANE FUNCTION Principal Investigator & Institution: Frangos, John A.; Principal Scientist; Bioengineering; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 30-JUN-2002 Summary: The overall goal of our research is to determine the molecular basis of mechanochemical signal transduction in endothelial cells. We have established that temporal gradients in shear stress and steady shear stress represent two distinct mechanical signals that are transduced by two different signaling pathways. The temporal gradient in shear stress has been shown to be a potent stimulator of mitogenic and pro-atherogenic signal and gene expression, and is mediated by the Gq heterotrimeric G protein. In contrast, steady shear stress appears to dose-dependently stimulate anti-atherogenic signals such as prostacyclin and nitric oxide. We hypothesize that mechanoreception of these two mechanical signals occurs at different spatial locations on the cell: temporal gradients in shear stress are perceived at the cell-cell junctions and steady shear is sensed over the luminal membrane. It is the objective of this proposal to elucidate the molecular events that lead to mechanoreception and mechanochemical transduction. Our first two specific aims are to elucidate the molecular associations and sequence of signaling events of Gq and endothelial nitric oxide synthase activation that occur at the cell-cell junctions as endothelial cells are subjected to temporal gradients in shear stress. The third specific aim is to investigate the spatial and temporal pattern of shear stress- induced changes in membrane microviscosity. To accomplish this, we will develop a technique to image membrane microenvironmental changes realtime in endothelial cells subjected to both temporal gradients in shear and steady shear stress. The fourth specific aim will determine if spatial gradients in shear stress do in fact stimulate a proatherogenic phenotype in human endothelial cells. This investigation will test a comprehensive hypothesis on the mechanism of mechanochemical transduction in endothelial cells. If successful, it will provide a fundamental understanding of how the endothelium senses hemodynamic forces in both normal physiology and in vascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIMVASTATIN APOB TURNOVER IN DIABETES Principal Investigator & Institution: Ginsberg, Henry N.; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIAL OF LOVASTATIN TO SLOW RATE OF PROGRESSION OF AD Principal Investigator & Institution: Sano, Mary; Professor of Neuropsychology; Columbia University New York, Ny 10017 Timing: Fiscal Year 2002 Summary: There is growing evidence from clinical, epidemiological and laboratory studies that cholesterol may play a role in the pathogenesis of Alzheimer's disease (AD).
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Based on this evidence we propose to conduct a double blind parallel group, placebocontrolled trial of lovastatin, a hydroxymethyul-glutaryl-(HMGA) CoA-reductase inhibitor that lowers plasma cholesterol and lipoprotein levels, in patients with AD. Patients will be assigned in a 1:1 ratio to receive drug (lovastatin dose: 40 mg/day) or identical placebo. Study duration will be 1 year followed by a 3-month washout period. The primary outcome measure will include ADCS-CGIC, Dependence Scale, MMSE, and Quality of Life-AD, ADCS pharmacoeconomic assessment, ADCS-ADL and the Neuropsychiatric Inventory. Apo E genotype will be done on all subjects. Biomarkers to assess the relationship between treatment response and, amyloid metabolism and inflammation will e assayed on a subst (N=100) of subjects. We will store samples for possible analysis of other, yet to be identified inflammatory and oxidative stress markers for the brain. To power the trial to detect a 33% difference. ADAScog decline (80% power, alpha=0.05, dropout estimate 20%), we will enroll a total of 300 subjects. 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 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 “lovastatin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for lovastatin in the PubMed Central database: •
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovastatin and simvastatin inhibit in vitro development of Plasmodium falciparum and Babesia divergens in human erythrocytes. by Grellier P, Valentin A, Millerioux V, Schrevel J, Rigomier D.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188165
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Antiviral Activity of Lovastatin against Respiratory Syncytial Virus In Vivo and In Vitro. by Gower TL, Graham BS.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90448
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Effects of lovastatin (mevinolin) on sterol levels and on activity of azoles in Saccharomyces cerevisiae. by Lorenz RT, Parks LW.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171901
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Lovastatin Biosynthesis by Aspergillus terreus in a Chemically Defined Medium. by Hajjaj H, Niederberger P, Duboc P.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92912
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
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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Lovastatin, an inhibitor of cholesterol synthesis, induces hydroxymethylglutarylcoenzyme A reductase directly on membranes of expanded smooth endoplasmic reticulum in rat hepatocytes. by Singer II, Scott S, Kazazis DM, Huff JW.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281730
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Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. by Rao S, Porter DC, Chen X, Herliczek T, Lowe M, Keyomarsi K.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22141
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Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. by Urbina JA, Lazardi K, Marchan E, Visbal G, Aguirre T, Piras MM, Piras R, Maldonado RA, Payares G, de Souza W.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187710
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Redistribution of the CDK inhibitor p27 between different cyclin.CDK complexes in the mouse fibroblast cell cycle and in cells arrested with lovastatin or ultraviolet irradiation. by Poon RY, Toyoshima H, Hunter T.; 1995 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301277
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 lovastatin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “lovastatin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for lovastatin (hyperlinks lead to article summaries): •
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A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients. Author(s): Hanes DS, Nicholson PG, Raval DD, Hooper FL, Behrens MT, Weir MR. Source: American Journal of Therapeutics. 1997 February-March; 4(2-3): 85-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10423597
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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A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extended-release and lovastatin. Author(s): Hunninghake DB, McGovern ME, Koren M, Brazg R, Murdock D, Weiss S, Pearson T. Source: Clin Cardiol. 2003 March; 26(3): 112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685616
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A multiple-dose pharmacodynamic, safety, and pharmacokinetic comparison of extended- and immediate-release formulations of lovastatin. Author(s): Davidson MH, Lukacsko P, Sun JX, Phillips G, Walters E, Sterman A, Niecestro R, Friedhoff L. Source: Clinical Therapeutics. 2002 January; 24(1): 112-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11833826
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A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme. Author(s): Larner J, Jane J, Laws E, Packer R, Myers C, Shaffrey M. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1998 December; 21(6): 579-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9856659
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A randomized, double-blind comparison of cerivastatin and lovastatin for treatment of primary hypercholesterolemia. Author(s): Yu WC, Chen CH, Tsao HM, Ding YA. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 June; 65(6): 260-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201566
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Action of an HMG CoA reductase inhibitor, lovastatin, on apoptosis of untransformed and ts-SV40 transformed human smooth muscle cells derived from saphenous vein. Author(s): Unlu S, Clunn G, Schachter M, Demoliou-Mason C, Hughes AD. Source: Journal of Cardiovascular Pharmacology. 2001 August; 38(2): 161-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11483865
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Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensinconverting enzyme inhibitors (enalapril or lisinopril). Author(s): Sposito AC, Mansur AP, Coelho OR, Nicolau JC, Ramires JA. Source: The American Journal of Cardiology. 1999 May 15; 83(10): 1497-9, A8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10335771
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Advicor (niacin extended-release and lovastatin tablets). Author(s): Scarpa WJ Jr. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2002 March-April; 4(2): 146. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927800
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Aggressive lipid lowering in postcoronary angioplasty patients with elevated cholesterol (the Lovastatin Restenosis Trial). Author(s): Boccuzzi SJ, Weintraub WS, Kosinski AS, Roehm JB, Klein JL. Source: The American Journal of Cardiology. 1998 March 1; 81(5): 632-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9514463
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Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin. Author(s): Downs JR, Clearfield M, Tyroler HA, Whitney EJ, Kruyer W, Langendorfer A, Zagrebelsky V, Weis S, Shapiro DR, Beere PA, Gotto AM. Source: The American Journal of Cardiology. 2001 May 1; 87(9): 1074-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11348605
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Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women. Author(s): Clearfield M, Downs JR, Weis S, Whitney EJ, Kruyer W, Shapiro DR, Stein EA, Langendorfer A, Beere PA, Gotto AM. Source: Journal of Women's Health & Gender-Based Medicine. 2001 December; 10(10): 971-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788107
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Allocation of resources between smoking cessation methods and lovastatin treatment of hypercholesterolaemia: based on cost effectiveness and the social welfare function. Author(s): Plans-Rubio P. Source: Pharmacoeconomics. 2004; 22(1): 55-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720082
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Antiatherosclerotic and antiatherogenic effects of a calcium antagonist plus statin combination: amlodipine and lovastatin. Author(s): Orekhov AN, Tertov VV, Sobenin IA, Akhmedzhanov NM, Pivovarova EM. Source: International Journal of Cardiology. 1997 December 31; 62 Suppl 2: S67-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9488197
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Lovastatin
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Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlidemia. Author(s): Zambrana JL, Lopez-Miranda J, Blanco A, Arizon JM, Jansen S, Paniagua JA, Jimenez-Pereperez JA, Concha M, Perez-Jimenez F. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1998 December; 17(12): 1213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9883763
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Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells. Author(s): Xia Z, Tan MM, Wong WW, Dimitroulakos J, Minden MD, Penn LZ. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 September; 15(9): 1398-407. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11516100
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By the way, doctor. I have high cholesterol, and have been taking Mevacor (lovastatin) for two years. Recently, I was switched to Pravachol (pravastatin) because my insurance company would no longer pay for Mevacor. Is it as good? Author(s): Nicholson CR. Source: Harvard Women's Health Watch. 1999 June; 6(10): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233830
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By the way, doctor. My brother takes Mevacor and has been told to take the drug at bedtime. But when I started on Lipitor, my doctor said to take the medication at any time of the day. Why the difference? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2001 August; 26(10): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11546623
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Cell-cycle gene expression in lovastatin-induced medulloblastoma apoptosis. Author(s): Wang W, Macaulay RJ. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 November; 30(4): 349-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672267
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Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin. Author(s): Wong WW, Tan MM, Xia Z, Dimitroulakos J, Minden MD, Penn LZ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 July; 7(7): 2067-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448925
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Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Author(s): Pincus J. Source: The American Journal of Cardiology. 1998 August 1; 82(3): 406-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9708683
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Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Author(s): Jones P, Kafonek S, Laurora I, Hunninghake D. Source: The American Journal of Cardiology. 1998 March 1; 81(5): 582-7. Erratum In: Am J Cardiol 1998 July 1; 82(1): 128. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9514454
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Comparative efficacy and tolerability of low-dose pravastatin versus lovastatin in patients with hypercholesterolemia. Author(s): Strauss WE, Lapsley D, Gaziano JM. Source: American Heart Journal. 1999 March; 137(3): 458-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10047626
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Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Author(s): Gentile S, Turco S, Guarino G, Sasso CF, Amodio M, Magliano P, Salvatore T, Corigliano G, Agrusta M, De Simone G, Gaeta I, Oliviero B, Torella R. Source: Diabetes, Obesity & Metabolism. 2000 December; 2(6): 355-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225965
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Comparative pharmacokinetics of lovastatin extended-release tablets and lovastatin immediate-release tablets in humans. Author(s): Sun JX, Niecestro R, Phillips G, Shen J, Lukacsko P, Friedhoff L. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 198-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831543
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Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. Author(s): Crespo N, Illnait J, Mas R, Fernandez L, Fernandez J, Castano G. Source: Int J Clin Pharmacol Res. 1999; 19(4): 117-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10939029
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Lovastatin
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Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Author(s): Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Benet LZ, Sewing KF, Christians U. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1999 February; 27(2): 173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929499
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Comparison of effect of intensive lipid lowering with atorvastatin to less intensive lowering with lovastatin on C-reactive protein in patients with stable angina pectoris and inducible myocardial ischemia. Author(s): Kinlay S, Timms T, Clark M, Karam C, Bilodeau T, Ridker PM, Rifai N, Carlson W, Lloyd-Jones DM, Johnstone M, Rubenstein J, Alexander S, Orav J, Stone PH; Vascular Basis Study Group. Source: The American Journal of Cardiology. 2002 May 15; 89(10): 1205-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008177
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Comparison of LDL trap assay to other tests of antioxidant capacity; effect of vitamin E and lovastatin treatment. Author(s): Malminiemi K, Palomaki A, Malminiemi O. Source: Free Radical Research. 2000 November; 33(5): 581-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11200090
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Comparison of the effects of pravastatin and lovastatin on sleep disturbance in hypercholesterolemic subjects. Author(s): Ehrenberg BL, Lamon-Fava S, Corbett KE, McNamara JR, Dallal GE, Schaefer EJ. Source: Sleep. 1999 February 1; 22(1): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9989373
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Comparison of the efficacy and safety of fenofibrate and lovastatin in patients with primary type IIa or IIb hyperlipidaemia. Author(s): Gholami K, Tavakoli N, Maleki M, Shafiee A. Source: Journal of Clinical Pharmacy and Therapeutics. 1998 June; 23(3): 213-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9831973
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Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Author(s): Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JL, Seman LJ, Ferrari A, Rubenstein JJ. Source: The American Journal of Cardiology. 2004 January 1; 93(1): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697462
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Conversion of patients from simvastatin to lovastatin in an outpatient pharmacy clinic. Author(s): Fugit RV, Resch ND. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 September 15; 57(18): 1703-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11006798
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Determination of lovastatin in human plasma using reverse-phase high-performance liquid chromatography with UV detection. Author(s): Ye LY, Firby PS, Moore MJ. Source: Therapeutic Drug Monitoring. 2000 December; 22(6): 737-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128243
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Differences between lovastatin and simvastatin hydrolysis in healthy male and female volunteers:gut hydrolysis of lovastatin is twice that of simvastatin. Author(s): Vree TB, Dammers E, Ulc I, Horkovics-Kovats S, Ryska M, Merkx I. Source: Scientificworldjournal. 2003 December 11; 3: 1332-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755114
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Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Author(s): Kivisto KT, Kantola T, Neuvonen PJ. Source: British Journal of Clinical Pharmacology. 1998 July; 46(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9690949
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Differential effects of lovastatin on the trafficking of endogenous and lipoproteinderived cholesterol in human monocyte-derived macrophages. Author(s): Cignarella A, Brennhausen B, von Eckardstein A, Assmann G, Cullen P. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1998 August; 18(8): 1322-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9714140
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Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. Author(s): Dimitroulakos J, Ye LY, Benzaquen M, Moore MJ, Kamel-Reid S, Freedman MH, Yeger H, Penn LZ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 January; 7(1): 158-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11205904
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Dose response, safety, and efficacy of an extended-release formulation of lovastatin in adults with hypercholesterolemia. Author(s): Crouse JR 3rd, Lukacsko P, Niecestro R, Friedhoff L. Source: The American Journal of Cardiology. 2002 January 15; 89(2): 226-9. Erratum In: Am J Cardiol 2000 June 15; 89(12): 1452. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11792349
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Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives. Author(s): Martinez-Botas J, Ferruelo AJ, Suarez Y, Fernandez C, Gomez-Coronado D, Lasuncion MA. Source: Biochimica Et Biophysica Acta. 2001 June 29; 1532(3): 185-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11470239
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Effect of atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglycerides in HepG2 cells. Author(s): Scharnagl H, Schinker R, Gierens H, Nauck M, Wieland H, Marz W. Source: Biochemical Pharmacology. 2001 December 1; 62(11): 1545-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728391
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Effect of colesevelam on lovastatin pharmacokinetics. Author(s): Donovan JM, Kisicki JC, Stiles MR, Tracewell WG, Burke SK. Source: The Annals of Pharmacotherapy. 2002 March; 36(3): 392-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895049
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Effect of cyclin E overexpression on lovastatin-induced G1 arrest and RhoA inactivation in NIH3T3 cells. Author(s): Ghosh PM, Moyer ML, Mott GE, Kreisberg JI. Source: Journal of Cellular Biochemistry. 1999 September 15; 74(4): 532-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10440923
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Effect of lovastatin on cardiovascular resource utilization and costs in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). AFCAPS/TexCAPS Research Group. Author(s): Gotto AM Jr, Boccuzzi SJ, Cook JR, Alexander CM, Roehm JB, Meyer GS, Clearfield M, Weis S, Whitney E. Source: The American Journal of Cardiology. 2000 December 1; 86(11): 1176-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11090787
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Effect of lovastatin on small GTP binding proteins and on TGF-beta1 and fibronectin expression. Author(s): Kim SI, Kim HJ, Han DC, Lee HB. Source: Kidney International. Supplement. 2000 September; 77: S88-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997696
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Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection. Author(s): Sahu K, Sharma R, Gupta A, Gulati S, Agarwal D, Kumar A, Bhandari M. Source: Clinical Transplantation. 2001 June; 15(3): 173-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11389707
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Effect of multiple cilostazol doses on single dose lovastatin pharmacokinetics in healthy volunteers. Author(s): Bramer SL, Brisson J, Corey AE, Mallikaarjun S. Source: Clinical Pharmacokinetics. 1999; 37 Suppl 2: 69-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702889
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Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers. Author(s): Bucher M, Mair G, Kees F. Source: European Journal of Clinical Pharmacology. 2002 January; 57(11): 787-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11868800
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Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. Author(s): Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Vidgen E, Lapsley KG, Trautwein EA, Josse RG, Leiter LA, Connelly PW. Source: Jama : the Journal of the American Medical Association. 2003 July 23; 290(4): 502-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12876093
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Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol. Author(s): Hung YJ, Pei D, Wu DA, Kuo SW, Fuh MM, Jeng C. Source: J Formos Med Assoc. 1999 February; 98(2): 104-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10083765
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Effects of lovastatin and pravastatin on cognitive function in military aircrew. Author(s): Gibellato MG, Moore JL, Selby K, Bower EA. Source: Aviation, Space, and Environmental Medicine. 2001 September; 72(9): 805-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11565814
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Effects of lovastatin and warfarin on early carotid atherosclerosis: sex-specific analyses. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Author(s): Byington RP, Evans GW, Espeland MA, Applegate WB, Hunninghake DB, Probstfield J, Furberg CD. Source: Circulation. 1999 July 20; 100(3): E14-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411862
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Effects of lovastatin on cognitive function and psychological well-being. Author(s): Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck SB. Source: The American Journal of Medicine. 2000 May; 108(7): 538-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806282
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Effects of lovastatin on progression of non-dilated and dilated coronary segments and on restenosis in patients after PTCA. The cholesterol lowering atherosclerosis PTCA trial (CLAPT) Author(s): Kleemann A, Eckert S, von Eckardstein A, Lepper W, Schernikau U, Gleichmann U, Hanrath P, Fleck E, Neiss A, Kerber S, Assmann G, Breithardt and the CLAPT Study. Source: European Heart Journal. 1999 October; 20(19): 1393-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487800
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Effects of lovastatin therapy on susceptibility of LDL to oxidation during alphatocopherol supplementation. Author(s): Palomaki A, Malminiemi K, Malminiemi O, Solakivi T. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 June; 19(6): 1541-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364087
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Effects of nicotinic acid and lovastatin in combination with cholestyramine in renal transplant patients. Author(s): Lal SM, Katyal A. Source: Mo Med. 2002 November-December; 99(10): 580-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534147
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Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. Author(s): Castano G, Mas R, Fernandez L, Gamez R, Illnait J. Source: Angiology. 2003 January; 54(1): 25-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593493
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Effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia associated with type 2 diabetes mellitus. Author(s): Castano G, Menendez R, Mas R, Amor A, Fernandez JL, Gonzalez RL, Lezcay M, Alvarez E. Source: Int J Clin Pharmacol Res. 2002; 22(3-4): 89-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837046
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Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Author(s): Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, Suresh R, Mukhopadhyay P, Veltri EP; Ezetimibe Study Group. Source: The American Journal of Cardiology. 2003 February 15; 91(4): 418-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586255
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Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. Author(s): Stein EA, Illingworth DR, Kwiterovich PO Jr, Liacouras CA, Siimes MA, Jacobson MS, Brewster TG, Hopkins P, Davidson M, Graham K, Arensman F, Knopp RH, DuJovne C, Williams CL, Isaacsohn JL, Jacobsen CA, Laskarzewski PM, Ames S, Gormley GJ. Source: Jama : the Journal of the American Medical Association. 1999 January 13; 281(2): 137-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9917116
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Epidermal growth factor receptor-targeted therapy potentiates lovastatin-induced apoptosis in head and neck squamous cell carcinoma cells. Author(s): Mantha AJ, McFee KE, Niknejad N, Goss G, Lorimer IA, Dimitroulakos J. Source: Journal of Cancer Research and Clinical Oncology. 2003 November; 129(11): 63141. Epub 2003 August 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942316
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Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Author(s): Kantola T, Kivisto KT, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 1998 April; 63(4): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9585793
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Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Author(s): Rogers JD, Zhao J, Liu L, Amin RD, Gagliano KD, Porras AG, Blum RA, Wilson MF, Stepanavage M, Vega JM. Source: Clinical Pharmacology and Therapeutics. 1999 October; 66(4): 358-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546919
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Grapefruit juice-lovastatin interaction. Author(s): Bailey DG, Dresser GK. Source: Clinical Pharmacology and Therapeutics. 2000 June; 67(6): 690. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10872652
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Growth inhibition of neuroblastoma cells by lovastatin and L-ascorbic acid is based on different mechanisms. Author(s): Girgert R, Vogt Y, Becke D, Bruchelt G, Schweizer P. Source: Cancer Letters. 1999 April 1; 137(2): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10374838
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Human lens cholesterol concentrations in patients who used lovastatin or simvastatin. Author(s): Mitchell J, Cenedella RJ. Source: Archives of Ophthalmology. 1999 May; 117(5): 653-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10326964
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Human multidrug-resistant (MRP,p190) myeloid leukemia HL-60/ADR cells in vitro: resistance to the mevalonate pathway inhibitor lovastatin. Author(s): Hunakova L, Sedlak J, Sulikova M, Chovancova J, Duraj J, Chorvath B. Source: Neoplasma. 1997; 44(6): 366-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9605009
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Impact of therapeutic interchange from pravastatin to lovastatin in a Veterans Affairs Medical Center. Author(s): Patel RJ, Gray DR, Pierce R, Jafari M. Source: Am J Manag Care. 1999 April; 5(4): 465-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10387386
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In response to Furst et al, “Possible association of QTc interval prolongation with coadministration of quetiapine and lovastatin”. Author(s): Geller W, Smith M, Winter H, Brecher M. Source: Biological Psychiatry. 2002 November 1; 52(9): 914; Author Reply 914-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399147
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Increased sensitivity of acute myeloid leukemias to lovastatin-induced apoptosis: A potential therapeutic approach. Author(s): Dimitroulakos J, Nohynek D, Backway KL, Hedley DW, Yeger H, Freedman MH, Minden MD, Penn LZ. Source: Blood. 1999 February 15; 93(4): 1308-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9949174
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Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to lovastatin. Author(s): Maksumova L, Ohnishi K, Muratkhodjaev F, Zhang W, Pan L, Takeshita A, Ohno R. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 August; 14(8): 1444-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10942241
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Increased sensitivity of myeloid leukemia cell lines: potential of lovastatin as bonemarrow-purging agent. Author(s): Scheffold C, Schottker B, Lefterova P, Csipai M, Glasmacher A, Huhn D, Neubauer A, Schmidt-Wolf IG. Source: Acta Haematologica. 2000; 104(2-3): 72-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11154978
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Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease. Author(s): Herrington DM, Werbel BL, Riley WA, Pusser BE, Morgan TM. Source: Journal of the American College of Cardiology. 1999 June; 33(7): 2030-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10362210
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Induction of apoptosis by lovastatin through activation of caspase-3 and DNase II in leukaemia HL-60 cells. Author(s): Wang IK, Lin-Shiau SY, Lin JK. Source: Pharmacology & Toxicology. 2000 February; 86(2): 83-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728920
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Inhibition of lovastatin on proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells. Author(s): Li H, Li X, Duan L, Li C. Source: Chinese Medical Journal. 2003 September; 116(9): 1366-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527367
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Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Author(s): Bouterfa HL, Sattelmeyer V, Czub S, Vordermark D, Roosen K, Tonn JC. Source: Anticancer Res. 2000 July-August; 20(4): 2761-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953355
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Interaction between lovastatin and cyclosporine A after heart and kidney transplantation. Author(s): Gullestad L, Nordal KP, Berg KJ, Cheng H, Schwartz MS, Simonsen S. Source: Transplantation Proceedings. 1999 August; 31(5): 2163-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10456002
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Interaction of cytosine arabinoside and lovastatin in human leukemia cells. Author(s): Holstein SA, Hohl RJ. Source: Leukemia Research. 2001 August; 25(8): 651-60. Erratum In: Leuk Res 2002 May; 26(5): 523. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11397469
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Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia. Author(s): Sanllehy C, Casals E, Rodriguez-Villar C, Zambon D, Ojuel J, Ballesta AM, Ros E. Source: Metabolism: Clinical and Experimental. 1998 May; 47(5): 560-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591747
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Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia. Author(s): Vazquez M, Zambon D, Hernandez Y, Adzet T, Merlos M, Ros E, Laguna JC. Source: British Journal of Clinical Pharmacology. 1998 March; 45(3): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9517370
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Long-term administration of the HMG-CoA reductase inhibitor lovastatin in two patients with cholesteryl ester storage disease. Author(s): Rassoul F, Richter V, Lohse P, Naumann A, Purschwitz K, Keller E. Source: Int J Clin Pharmacol Ther. 2001 May; 39(5): 199-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380065
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Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Author(s): Kashyap ML, McGovern ME, Berra K, Guyton JR, Kwiterovich PO, Harper WL, Toth PD, Favrot LK, Kerzner B, Nash SD, Bays HE, Simmons PD. Source: The American Journal of Cardiology. 2002 March 15; 89(6): 672-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897208
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Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Author(s): Tobert JA. Source: Nature Reviews. Drug Discovery. 2003 July; 2(7): 517-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815379
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Lovastatin and extended-release niacin combination product: the first drug combination for the management of hyperlipidemia. Author(s): Gupta EK, Ito MK. Source: Heart Disease. 2002 March-April; 4(2): 124-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11975844
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Lovastatin and phenylacetate induce apoptosis, but not differentiation, in human malignant glioma cells. Author(s): Schmidt F, Groscurth P, Kermer M, Dichgans J, Weller M. Source: Acta Neuropathologica. 2001 March; 101(3): 217-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307620
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Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen. Author(s): Bank I, Koltakov A, Nir-Glickman E, Goldstein I, Li J, Roitelman J, Chess L. Source: Cellular Immunology. 2003 May; 223(1): 35-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12914756
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Lovastatin and sodium phenylacetate normalize the levels of very long chain fatty acids in skin fibroblasts of X- adrenoleukodystrophy. Author(s): Singh I, Pahan K, Khan M. Source: Febs Letters. 1998 April 24; 426(3): 342-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600263
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Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Author(s): Feleszko W, Jakobisiak M. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 March; 6(3): 1198-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10741752
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Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Author(s): Agarwal B, Bhendwal S, Halmos B, Moss SF, Ramey WG, Holt PR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 August; 5(8): 2223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10473109
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Lovastatin causes sensitization of HeLa cells to ionizing radiation-induced apoptosis by the abrogation of G2 blockage. Author(s): Fritz G, Brachetti C, Kaina B. Source: International Journal of Radiation Biology. 2003 August; 79(8): 601-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555343
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Lovastatin decreases the receptor-mediated degradation of acetylated and oxidized LDLs in human blood monocytes during the early stage of differentiation into macrophages. Author(s): Hrboticky N, Draude G, Hapfelmeier G, Lorenz R, Weber PC. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 May; 19(5): 1267-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323779
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Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Author(s): Park IH, Hwang EM, Hong HS, Boo JH, Oh SS, Lee J, Jung MW, Bang OY, Kim SU, Mook-Jung I. Source: Neurobiology of Aging. 2003 September; 24(5): 637-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885571
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Lovastatin enhances ecto-5'-nucleotidase activity and cell surface expression in endothelial cells: implication of rho-family GTPases. Author(s): Ledoux S, Laouari D, Essig M, Runembert I, Trugnan G, Michel JB, Friedlander G. Source: Circulation Research. 2002 March 8; 90(4): 420-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11884371
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Lovastatin extended release: a review of its use in the management of hypercholesterolaemia. Author(s): Curran MP, Goa KL. Source: Drugs. 2003; 63(7): 685-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656649
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Lovastatin for X-linked adrenoleukodystrophy. Author(s): Singh I, Khan M, Key L, Pai S. Source: The New England Journal of Medicine. 1998 September 3; 339(10): 702-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9729143
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Lovastatin induced control of blast cell growth in an elderly patient with acute myeloblastic leukemia. Author(s): Minden MD, Dimitroulakos J, Nohynek D, Penn LZ. Source: Leukemia & Lymphoma. 2001 February; 40(5-6): 659-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11426537
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Lovastatin induces a pronounced differentiation response in acute myeloid leukemias. Author(s): Dimitroulakos J, Thai S, Wasfy GH, Hedley DW, Minden MD, Penn LZ. Source: Leukemia & Lymphoma. 2000 December; 40(1-2): 167-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11426618
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Lovastatin induces apoptosis in a primitive neuroectodermal tumor cell line in association with RB down-regulation and loss of the G1 checkpoint. Author(s): Kim JS, Pirnia F, Choi YH, Nguyen PM, Knepper B, Tsokos M, Schulte TW, Birrer MJ, Blagosklonny MV, Schaefer O, Mushinski JF, Trepel JB. Source: Oncogene. 2000 December 7; 19(52): 6082-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146561
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Lovastatin induces apoptosis in malignant mesothelioma cells. Author(s): Rubins JB, Greatens T, Kratzke RA, Tan AT, Polunovsky VA, Bitterman P. Source: American Journal of Respiratory and Critical Care Medicine. 1998 May; 157(5 Pt 1): 1616-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603146
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Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Author(s): Zhong WB, Wang CY, Chang TC, Lee WS. Source: Endocrinology. 2003 September; 144(9): 3852-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933658
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Lovastatin induces fibroblast apoptosis in vitro and in vivo. A possible therapy for fibroproliferative disorders. Author(s): Tan A, Levrey H, Dahm C, Polunovsky VA, Rubins J, Bitterman PB. Source: American Journal of Respiratory and Critical Care Medicine. 1999 January; 159(1): 220-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9872842
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Lovastatin induces mitotic abnormalities in various cell lines. Author(s): Lamprecht J, Wojcik C, Jakobisiak M, Stoehr M, Schrorter D, Paweletz N. Source: Cell Biology International. 1999; 23(1): 51-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10527548
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Lovastatin induces p21WAF1/Cip1 in human vascular smooth muscle cells: influence on protein phosphorylation, cell cycle, induction of apoptosis, and growth inhibition. Author(s): Muller C, Kiehl MG, van de Loo J, Koch OM. Source: International Journal of Molecular Medicine. 1999 January; 3(1): 63-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9864387
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Lovastatin inhibits G1/S transition of normal human B-lymphocytes independent of apoptosis. Author(s): Naderi S, Blomhoff R, Myklebust J, Smeland EB, Erikstein B, Norum KR, Blomhoff HK. Source: Experimental Cell Research. 1999 October 10; 252(1): 144-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10502407
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Lovastatin inhibits proliferation of pancreatic cancer cell lines with mutant as well as with wild-type K-ras oncogene but has different effects on protein phosphorylation and induction of apoptosis. Author(s): Muller C, Bockhorn AG, Klusmeier S, Kiehl M, Roeder C, Kalthoff H, Koch OM. Source: International Journal of Oncology. 1998 March; 12(3): 717-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9472115
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Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion. Author(s): Nubel T, Dippold W, Kleinert H, Kaina B, Fritz G. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2004 January; 18(1): 140-2. Epub 2003 November 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14630701
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Lovastatin is a potent inhibitor of meningioma cell proliferation: evidence for inhibition of a mitogen associated protein kinase. Author(s): Johnson MD, Woodard A, Okediji EJ, Toms SA, Allen GS. Source: Journal of Neuro-Oncology. 2002 January; 56(2): 133-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11995814
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Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53. Author(s): Rao S, Lowe M, Herliczek TW, Keyomarsi K. Source: Oncogene. 1998 November 5; 17(18): 2393-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9811471
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Lovastatin potentiates antitumor activity of doxorubicin in murine melanoma via an apoptosis-dependent mechanism. Author(s): Feleszko W, Mlynarczuk I, Olszewska D, Jalili A, Grzela T, Lasek W, Hoser G, Korczak-Kowalska G, Jakobisiak M. Source: International Journal of Cancer. Journal International Du Cancer. 2002 July 1; 100(1): 111-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115596
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Lovastatin stimulates human vascular smooth muscle cell expression of bone morphogenetic protein-2, a potent inhibitor of low-density lipoprotein-stimulated cell growth. Author(s): Emmanuele L, Ortmann J, Doerflinger T, Traupe T, Barton M. Source: Biochemical and Biophysical Research Communications. 2003 February 28; 302(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593849
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Lovastatin therapy for X-linked adrenoleukodystrophy: clinical and biochemical observations on 12 patients. Author(s): Pai GS, Khan M, Barbosa E, Key LL, Craver JR, Cure JK, Betros R, Singh I. Source: Molecular Genetics and Metabolism. 2000 April; 69(4): 312-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10870849
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Lovastatin to prevent acute coronary events with average cholesterol levels. Author(s): MacFarlane LL, Carek PJ. Source: The Journal of Family Practice. 1998 August; 47(2): 91-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9722787
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Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, induces apoptosis and differentiation in human anaplastic thyroid carcinoma cells. Author(s): Wang CY, Zhong WB, Chang TC, Lai SM, Tsai YF. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3021-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843138
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Lovastatin-induced apoptosis in thyroid cells: involvement of cytochrome c and lamin B. Author(s): Di Matola T, D'Ascoli F, Luongo C, Bifulco M, Rossi G, Fenzi G, Vitale M. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2001 November; 145(5): 645-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720884
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Lovastatin-induced apoptosis of human medulloblastoma cell lines in vitro. Author(s): Macaulay RJ, Wang W, Dimitroulakos J, Becker LE, Yeger H. Source: Journal of Neuro-Oncology. 1999 March; 42(1): 1-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10360474
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Lovastatin-induced cytoskeletal reorganization in lens epithelial cells: role of Rho GTPases. Author(s): Maddala RL, Reddy VN, Rao PV. Source: Investigative Ophthalmology & Visual Science. 2001 October; 42(11): 2610-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11581207
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Lovastatin-induced E2F-1 modulation and its effect on prostate cancer cell death. Author(s): Park C, Lee I, Kang WK. Source: Carcinogenesis. 2001 October; 22(10): 1727-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11577016
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Lovastatin-induced inhibition of HL-60 cell proliferation via cell cycle arrest and apoptosis. Author(s): Park WH, Lee YY, Kim ES, Seol JG, Jung CW, Lee CC, Kim BK. Source: Anticancer Res. 1999 July-August; 19(4B): 3133-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10652602
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Lovastatin-induced proliferation inhibition and apoptosis in C6 glial cells. Author(s): Choi JW, Jung SE. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 April; 289(1): 572-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10087052
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Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Author(s): Rao S, Porter DC, Chen X, Herliczek T, Lowe M, Keyomarsi K. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 July 6; 96(14): 7797-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393901
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Lovastatin-stimulated superinduction of E-selectin, ICAM-1 and VCAM-1 in TNFalpha activated human vascular endothelial cells. Author(s): Schmidt A, Goepfert C, Feitsma K, Buddecke E. Source: Atherosclerosis. 2002 September; 164(1): 57-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12119193
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Low density lipoproteins and Lovastatin modulate the organ-specific transendothelial migration of primary and metastatic human colon adenocarcinoma cell lines in vitro. Author(s): Mehta N, Hordines J, Sykes D, Doerr RJ, Cohen SA. Source: Clinical & Experimental Metastasis. 1998 October; 16(7): 587-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9932605
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Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin. Author(s): Massy ZA, Kim Y, Guijarro C, Kasiske BL, Keane WF, O'Donnell MP. Source: Biochemical and Biophysical Research Communications. 2000 January 19; 267(2): 536-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631097
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Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia. Author(s): Davidson MH, Toth P, Weiss S, McKenney J, Hunninghake D, Isaacsohn J, Donovan JM, Burke SK. Source: Clin Cardiol. 2001 June; 24(6): 467-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11403509
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Mevalonate prevents lovastatin-induced apoptosis in medulloblastoma cell lines. Author(s): Wang W, Macaulay RJ. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1999 November; 26(4): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10563217
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Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Author(s): Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P, Penn LZ, Kamel-Reid S. Source: Neoplasia (New York, N.Y.). 2002 July-August; 4(4): 337-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12082550
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Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy. Author(s): Wong PW, Dillard TA, Kroenke K. Source: Southern Medical Journal. 1998 February; 91(2): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9496876
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Niacin extended-release/lovastatin: combination therapy for lipid disorders. Author(s): Moon YS, Kashyap ML. Source: Expert Opinion on Pharmacotherapy. 2002 December; 3(12): 1763-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472373
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Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed dyslipidemia. Author(s): Yim BT, Chong PH. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 106-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503944
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Once-daily niacin extended release/lovastatin combination tablet has more favorable effects on lipoprotein particle size and subclass distribution than atorvastatin and simvastatin. Author(s): Bays HE, McGovern ME. Source: Preventive Cardiology. 2003 Fall; 6(4): 179-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605511
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Pharmacokinetics of lovastatin extended-release dosage form (Lovastatin XL) in healthy volunteers. Author(s): Lamson M, Phillips G, Shen J, Lukacsko P, Friedhoff L, Niecestro RM. Source: Biopharmaceutics & Drug Disposition. 2002 May; 23(4): 143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015788
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Pharmacological concentrations of the HMG-CoA reductase inhibitor lovastatin decrease the formation of the Alzheimer beta-amyloid peptide in vitro and in patients. Author(s): Buxbaum JD, Cullen EI, Friedhoff LT. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 April 1; 7: A50-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11900994
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Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Author(s): Thibault A, Samid D, Tompkins AC, Figg WD, Cooper MR, Hohl RJ, Trepel J, Liang B, Patronas N, Venzon DJ, Reed E, Myers CE. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1996 March; 2(3): 483-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9816194
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Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Author(s): Kim WS, Kim MM, Choi HJ, Yoon SS, Lee MH, Park K, Park CH, Kang WK. Source: Investigational New Drugs. 2001; 19(1): 81-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291836
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Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Author(s): Kyrklund C, Backman JT, Kivisto KT, Neuvonen M, Laitila J, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 2001 May; 69(5): 340-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11372002
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Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin. Author(s): Furst BA, Champion KM, Pierre JM, Wirshing DA, Wirshing WC. Source: Biological Psychiatry. 2002 February 1; 51(3): 264-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11839370
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Potent suppression of proliferation of a10 vascular smooth muscle cells by combined treatment with lovastatin and 3-allylfarnesol, an inhibitor of protein farnesyltransferase. Author(s): Mattingly RR, Gibbs RA, Menard RE, Reiners JJ Jr. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 October; 303(1): 74-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235235
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Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. Author(s): Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr. Source: Jama : the Journal of the American Medical Association. 1998 May 27; 279(20): 1615-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9613910
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Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: additive effects of combination treatment on lipid regulation. Author(s): Zambon D, Ros E, Rodriguez-Villar C, Laguna JC, Vazquez M, Sanllehy C, Casals E, Sol JM, Hernandez G. Source: Metabolism: Clinical and Experimental. 1999 January; 48(1): 47-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9920144
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Recent advances in the biosynthetic studies of lovastatin. Author(s): Sutherland A, Auclair K, Vederas JC. Source: Curr Opin Drug Discov Devel. 2001 March; 4(2): 229-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11378962
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Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. Author(s): Pappu AS, Bacon SP, Illingworth DR. Source: The Journal of Laboratory and Clinical Medicine. 2003 April; 141(4): 250-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677170
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Role of isoprenylation in the inhibitory action of lovastatin on proliferation of SV40 immortalized human saphenous vein smooth muscle cells. Author(s): Unlu S, Mason CD, Hughes AD. Source: Biochemical Society Transactions. 1998 November; 26(4): S324. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10047838
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Safety and efficacy of treatment of children and adolescents with elevated low density lipoprotein levels with a step two diet or with lovastatin. Author(s): Kwiterovich PO Jr. Source: Nutr Metab Cardiovasc Dis. 2001 October; 11 Suppl 5: 30-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063773
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Short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes mellitus and mixed dyslipidemia. Author(s): Ko GT, Mak TW, Yeung VT, Chan DC, Lam CW, Tsang LW, Chow CC, Cockram CS. Source: Journal of Clinical Pharmacology. 1998 October; 38(10): 912-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9807971
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Small intestinal metabolism of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin and comparison with pravastatin. Author(s): Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Baner K, Benet LZ, Sewing KF, Christians U. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 October; 291(1): 131-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10490896
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Stimulation of platelets and endothelial cells by mildly oxidized LDL proceeds through activation of lysophosphatidic acid receptors and the Rho/Rho-kinase pathway. Inhibition by lovastatin. Author(s): Essler M, Retzer M, Bauer M, Zangl KJ, Tigyi G, Siess W. Source: Annals of the New York Academy of Sciences. 2000 April; 905: 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10818465
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Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. Author(s): Kallen J, Welzenbach K, Ramage P, Geyl D, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U. Source: Journal of Molecular Biology. 1999 September 10; 292(1): 1-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10493852
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Synergistic interaction between highly specific cyclooxygenase-2 inhibitor, MFtricyclic and lovastatin in murine colorectal cancer cell lines. Author(s): Feleszko W, Jalili A, Olszewska D, Mlynarczuk I, Grzela T, Giermasz A, Jakobisiak M. Source: Oncol Rep. 2002 July-August; 9(4): 879-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12066226
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Synergistic interaction of lovastatin and paclitaxel in human cancer cells. Author(s): Holstein SA, Hohl RJ. Source: Molecular Cancer Therapeutics. 2001 December; 1(2): 141-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12467231
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The cholesterol lowering drug lovastatin induces cell death in myeloma plasma cells. Author(s): van de Donk NW, Kamphuis MM, Lokhorst HM, Bloem AC. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 July; 16(7): 1362-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094262
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The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin. Author(s): Koren MJ, Smith DG, Hunninghake DB, Davidson MH, McKenney JM, Weiss SR, Schrott HG, Henley RW Jr, Tresh P, McLain RW, Bakker-Arkema RG, Black DM. Source: Pharmacoeconomics. 1998 July; 14(1): 59-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10182195
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The effect of the apolipoprotein E phenotype on cholesteryl ester transfer protein activity, plasma lipids and apolipoprotein A I levels in hypercholesterolaemic patients on colestipol and lovastatin treatment. Author(s): Korhonen T, Hannuksela ML, Seppanen S, Kervinen K, Kesaniemi YA, Savolainen MJ. Source: European Journal of Clinical Pharmacology. 1999 February; 54(12): 903-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10192749
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The effects of lovastatin and simvastatin on the diurnal periodicity of plasma mevalonate concentrations in patients with heterozygous familial hypercholesterolemia. Author(s): Pappu AS, Illingworth DR. Source: Atherosclerosis. 2002 November; 165(1): 137-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208479
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The effects of the statins lovastatin and cerivastatin on signalling by the prostanoid IP-receptor. Author(s): Lawler OA, Miggin SM, Kinsella BT. Source: British Journal of Pharmacology. 2001 April; 132(8): 1639-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11309234
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The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its down-regulation by lovastatin. Author(s): Draude G, Hrboticky N, Lorenz RL. Source: Biochemical Pharmacology. 1999 February 15; 57(4): 383-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9933026
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The interaction of diltiazem with lovastatin and pravastatin. Author(s): Azie NE, Brater DC, Becker PA, Jones DR, Hall SD. Source: Clinical Pharmacology and Therapeutics. 1998 October; 64(4): 369-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9797793
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The liver and lovastatin. Author(s): Tolman KG. Source: The American Journal of Cardiology. 2002 June 15; 89(12): 1374-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12062731
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The widening role of statins: RAS signal transduction and drug-induced cytotoxicity in human leukemia: a commentary to 'interaction of cytosine arabinoside and lovastatin in human leukemia cells'. Author(s): Braess J, Hiddemann W. Source: Leukemia Research. 2001 August; 25(8): 661-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11397470
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Therapeutic potential of lovastatin in multiple sclerosis. Author(s): Sena A, Pedrosa R, Graca Morais M. Source: Journal of Neurology. 2003 June; 250(6): 754-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12862032
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Therapy of hyperlipidemia with lovastatin in kidney transplant patients on cyclosporine A immunosuppression: three-year experience. Author(s): Kandus A, Kovac D, Cerne D, Koselj M, Kaplan-Pavlovcic S, Buturovic J, Ponikvar R, Kveder R, Lindic J, Bren AF. Source: Transplantation Proceedings. 1998 June; 30(4): 1307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636530
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Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach. Author(s): Berglund L, Witztum JL, Galeano NF, Khouw AS, Ginsberg HN, Ramakrishnan R. Source: Journal of Lipid Research. 1998 April; 39(4): 913-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9555954
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Treating hyperlipidemia for the primary prevention of coronary disease. Are higher dosages of lovastatin cost-effective? Author(s): Perreault S, Hamilton VH, Lavoie F, Grover S. Source: Archives of Internal Medicine. 1998 February 23; 158(4): 375-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9487235
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Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. Author(s): Brown AS, Bakker-Arkema RG, Yellen L, Henley RW Jr, Guthrie R, Campbell CF, Koren M, Woo W, McLain R, Black DM. Source: Journal of the American College of Cardiology. 1998 September; 32(3): 665-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741509
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Treating to meet NCEP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease. Author(s): Hunninghake D, Bakker-Arkema RG, Wigand JP, Drehobl M, Schrott H, Early JL, Abdallah P, McBride S, Black DM. Source: The Journal of Family Practice. 1998 November; 47(5): 349-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9834769
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Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide. Author(s): Friedhoff LT, Cullen EI, Geoghagen NS, Buxbaum JD. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2001 June; 4(2): 127-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11466161
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Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo. Author(s): Palomaki A, Malminiemi K, Solakivi T, Malminiemi O. Source: Journal of Lipid Research. 1998 July; 39(7): 1430-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9684746
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CHAPTER 2. NUTRITION AND LOVASTATIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and lovastatin.
Finding Nutrition Studies on Lovastatin 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 “lovastatin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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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 information is typical of that found when using the “Full IBIDS Database” to search for “lovastatin” (or a synonym): •
A comparative study of policosanol vs lovastatin on intimal thickening in rabbit cuffed carotid artery. Author(s): Department of Pharmacology, Center of Natural Products, National Center for Scientific Research, Havana, Cuba.
[email protected] Source: Noa, M Mas, R Mesa, R Pharmacol-Res. 2001 January; 43(1): 31-7 1043-6618
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Effect of lovastatin or niacin combined with colestipol and regression of coronary atherosclerosis. Author(s): Cardiology Division, University of Washington, Seattle 98195. Source: Brown, B G Eur-Heart-J. 1992 July; 13 Suppl B17-20 0195-668X
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Effects of lovastatin and pravastatin on the survival of hamsters with inherited cardiomyopathy. Author(s): Division of Clinical Chemistry, Department of Medicine, Albert LudwigsUniversity, Freiburg, Germany.
[email protected] Source: Marz, W Siekmeier, R Muller, H M Wieland, H Gross, W Olbrich, H G JCardiovasc-Pharmacol-Ther. 2000 October; 5(4): 275-9 1074-2484
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Efficacy, safety and tolerability of lovastatin and bezafibrate retard in patients with hypercholesterolemia. Author(s): Abteilung fur Kardiologie, Medizinische Universitatsklinik Graz. Source: Schumacher, M Eber, B Silberbauer, K Breier, C Stuhlinger, W Schmidt, P Gaul, G Klein, W Acta-Med-Austriaca. 1992; 19(5): 140-4 0303-8173
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HMG CoA reductase inhibitors as lipid-lowering agents: five years experience with lovastatin and an appraisal of simvastatin and pravastatin. Author(s): MRC Lipoprotein Team, Hammersmith Hospital, London. Source: Maher, V M Thompson, G R Q-J-Med. 1990 February; 74(274): 165-75 0033-5622
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Lovastatin and gemfibrozil in the treatment of type 2a and type 2b hyperlipoproteinemia. Author(s): First Department of Medicine, University of Helsinki, Finland. Source: Tikkanen, M J Ojala, J P Helve, E Eur-J-Clin-Pharmacol. 1991; 40 Suppl 1S23-5 0031-6970
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Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition. Author(s): Institute for Arteriosclerosis Research, University of Munster, Germany.
[email protected] Source: Skaletz Rorowski, A Muller, J G Kroke, A Waltenberger, J Pulawski, E Pinkernell, K Breithardt, G Eur-J-Cell-Biol. 2001 March; 80(3): 207-12 0171-9335
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Lovastatin is a potent inhibitor of cholecystokinin secretion in endocrine tumor cells in culture. Author(s): Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. Source: Vishnuvardhan, D Beinfeld, M C Peptides. 2000 April; 21(4): 553-7 0196-9781
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Low plasma lipid levels and increased cholesterol synthesis after partial ileal bypass plus lovastatin in hypercholesterolemic rabbits. Author(s): Department of Surgery, University of Minnesota Health Sciences Center, Minneapolis 55455. Source: Tijerina, O Dombrovskis, S Esper, E Matts, J P Campos, C T Buchwald, H Surgery. 1988 October; 104(4): 796-805 0039-6060
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On call. I am 58 years old. I've always been healthy, but my doctor found that my cholesterol was 279. He prescribed Mevacor, and my cholesterol came down to 210. Do I still need to be on a low-fat diet? Source: Simon, H B Harv-Mens-Health-Watch. 2000 August; 5(1): 8 1089-1102
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Pravastatin and lovastatin similarly reduce serum cholesterol and its precursor levels in familial hypercholesterolaemia. Author(s): Second Department of Medicine, University of Helsinki, Finland. Source: Vanhanen, H Miettinen, T A Eur-J-Clin-Pharmacol. 1992; 42(2): 127-30 0031-6970
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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WebMDHealth: 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 lovastatin; 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 Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Atorvastatin Source: Healthnotes, Inc.; www.healthnotes.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; http://www.drkoop.com/
Nutrition
Fluvastatin Source: Healthnotes, Inc.; www.healthnotes.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com HMG-CoA Reductase Inhibitors (Statins) Source: Integrative Medicine Communications; www.drkoop.com Lovastatin Source: Healthnotes, Inc.; www.healthnotes.com Pravastatin Source: Healthnotes, Inc.; www.healthnotes.com Retinol Alternative names: Vitamin A (Retinol) Source: Integrative Medicine Communications; www.drkoop.com Simvastatin Source: Healthnotes, Inc.; www.healthnotes.com Statin Drugs Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin A (Retinol) Alternative names: Retinol Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. CLINICAL TRIALS AND LOVASTATIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning lovastatin.
Recent Trials on Lovastatin The following is a list of recent trials dedicated to lovastatin.8 Further information on a trial is available at the Web site indicated. •
Effect of Niacin Extended Release and Lovastatin tablets on Walking in Patients with Intermittent Claudication (ICPOP) Condition(s): Intermittent Claudication; Peripheral Vascular Disease Study Status: This study is currently recruiting patients. Sponsor(s): Kos Pharmaceuticals Purpose - Excerpt: You are being asked to participate in a research study that will determine if Niacin ER/Lovastatin at two different doses compared to diet control (this group will receive a tablet containing 50 mg. of immediate-release niacin) is a safe medicine that will reduce leg pain in subjects with intermittent claudication. Niacin ER/Lovastatin is a combination of two FDA (United States Food and Drug Administration) approved cholesterol modifying medications: Niaspan(r) (extendedrelease niacin) and lovastatin, a statin (the same medicine found in Mevacor(r)). Niacin ER/Lovastatin was approved by the FDA under the name of AdvicorTM for use in the treatment of elevated cholesterol. The use of Niacin ER/Lovastatin in the treatment of peripheral arterial disease and symptomatic relief of intermittent claudication is considered investigational. An investigational use is one that is not approved by the FDA. At least 375 subjects, with a similar medical condition to yours will participate in this study. This study will use competitive enrollment. This means that when a target number of subjects have entered the treatment phase of the study, all further enrollment will be closed. Therefore, it is possible that you could be in the screening phase, and be discontinued without your consent if the target number of subjects have already entered
8
These are listed at www.ClinicalTrials.gov.
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the study. The purpose of this study is to evaluate the effect of Niacin ER/Lovastatin (at two different doses) compared with a diet-only control group in subjects with intermittent claudication (leg pain), a condition caused by narrowing of the leg arteries. Duration of the Study You will be monitored for up to six (6) weeks in order to determine if you qualify for the study. During the six-week qualification period, you will return to the study center for 3-4 study visits. Qualification for the study includes: *having experienced "intermittent claudication" (leg pain) for at least 6 months *3-4 treadmill tests (walking tests) *determination of your legs' blood pressure. If you qualify and choose to participate, your participation in this study will last approximately nineteen months. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062556 •
Phase II Study of Cholesterol- and Cholestanol-Free Diet, Lovastatin, and Chenodeoxycholic Acid for Cerebrotendinous Xanthomatosis Condition(s): Cerebrotendinous Xanthomatosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Oregon Health and Science University Purpose - Excerpt: Objectives: I. Assess the biosynthesis of cholesterol and cholestanol, and measure the turnover of individual sterols and bile acids in patients with cerebrotendinous xanthomatosis before and after a cholesterol- and cholestanol-free diet. II. Assess the biosynthesis of cholesterol and cholestanol, and measure the turnover of individual sterols and bile acids in these patients before and after lovastatin and chenodeoxycholic acid. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004346
•
The Dose Response of Niacin ER/Lovastatin on Peak Walking Time (PWT) in Patients with Intermittent Claudication - TROPIC Condition(s): Intermittent Claudication; Peripheral Vascular Disease Study Status: This study is currently recruiting patients. Sponsor(s): Kos Pharmaceuticals Purpose - Excerpt: The purpose of this study is to compare the dose response and safety of Niacin ER/Lovastatin, Niaspan and Lovastatin with each other and to a diet-only control group, in subjects with leg pain caused by a narrowing of their leg arteries. At least 1320 subjects, with leg pain caused by a narrowing of their leg arteries will take part in this study. Both Niaspan and Lovastatin (Mevacor(r)) are approved by the United States Food and Drug Administration (FDA) to treat high cholesterol. Niacin ER/Lovastatin (AdvicorTM), a combination of these two drugs, is also approved by the FDA to treat high cholesterol. The use of Niacin ER/Lovastatin to treat narrowing of leg arteries and relieve "intermittent claudication" (leg pain caused by narrowing of the
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arteries in the leg) is considered investigational. An investigational use is one that is not approved by the FDA. Phase(s): Phase III Study Type: Interventional Contact(s): Craig F Amburgey, MS (800) 722-4567 Web Site: http://clinicaltrials.gov/ct/show/NCT00071266
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 “lovastatin” (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/
•
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 4. PATENTS ON LOVASTATIN 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 “lovastatin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lovastatin, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Lovastatin By performing a patent search focusing on lovastatin, 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 will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on lovastatin: •
Amelioration of reductions of coenzyme Q.sub.10 in cardiomyopathy patients receiving lovastatin Inventor(s): Folkers; Karl A. (6406 Mesa Dr., Austin, TX 78731), Langsjoen; Per H. (3005 El Camino Dr., Temple, TX 76502) Assignee(s): None Reported Patent Number: 5,082,650 Date filed: September 7, 1989 Abstract: The present invention comprises the serious side effect of mevinolin to depress body levels of coenzyme Q.sub.10 and to correspondingly depress cardiac function and the circumvention of this side effect by the clinical administration of a formulation of coenzyme Q.sub.10 concommitantly with the administration of the mevinolin. Excerpt(s): This invention relates to a newly discovered reduction in levels of coenzyme Q.sub.10 in human subjects which is a side effect from the administration of MEVACOR (lovastatin). The reduction of tissue levels of coenzyme Q.sub.10 by oral MEVACOR can in turn cause an increase in cardiac dysfunction, and for patients with advanced cardiac disease, this added dysfunction can be life-threatening. Also, a reduction in levels of CoQ.sub.10 in human subjects by MEVACOR can depress other essential functions in the human body such as the immune function which can also be very clinically serious and even life-threatening, particularly for any cancer patient. Coronary artery disease is the major cause of death in Western countries. Hypercholesterolemia is known to be a primary risk factor for death from coronary artery disease. It is known that 50% or more of the total body cholesterol in humans is derived from intrinsic biosynthesis. It is also known that a rate-limiting step of major significance in the biosynthesis of cholesterol is at the level of the enzyme known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase or HMG-CoA reductase. This enzyme then was logical for inhibition to reduce the intrinsic biosynthesis of cholesterol toward reducing the risk factor of hypercholesterolemia and coronary artery death. The Product Monograph on MEVACOR by Merck, Sharp and Dohme (issued May 1988, DC 7489503) states that MEVACOR is highly effective in the treatment of hypercholesterolemia. Further, at maximum doses, MEVACOR produced a mean reduction of LDL cholesterol of 39% in two large multicenter control studies. In general, MEVACOR was found to be welltolerated in continuing extensive clinical trials as based on data from studies worldwide. However, approximately 2% of patients were discontinued from therapy due to drugrelated adverse effects in all clinical studies. The most frequently reported adverse experiences were: headache (9.3%), flatus (6.4%), abdominal pain/cramps (5.7%), diarrhea (5.5%) and rash/pruritus (5.2%) (page 66). Web site: http://www.delphion.com/details?pn=US05082650__
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•
Biosynthetic production of 7-[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)hydroxy-1' (S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid) Inventor(s): Cianciosi; Steven J. (Harrisonburg, VA), Conder; Michael J. (Harrisonburg, VA), Cover; William H. (Lansdale, PA), Dabora; Rebecca L. (Andover, MA), Pisk; Eric T. (Harrisonburg, VA), Stieber; Robert W. (Harrisonburg, VA), Tehlewitz; Bogdan (McGaheysville, VA), Tewalt; Gregory L. (Shenandoah, VA) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 5,223,415 Date filed: February 7, 1992 Abstract: Biosynthetic production of 7-[1',2',6',-7',8',8a'(R)-hexahydro-2'(S),6'(R)dimethyl-8'(S)-hydroxy-1'( S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid, "triol acid", is accomplished by enzymatic hydrolysis of lovastatin acid or a salt thereof, by treating it with Clonostachys compactiuscula ATCC 38009 or ATCC 74178, or mutants thereof, or a cell-free extract derived therefrom, or a hydrolase derived therefrom. The triol acid and its lactone form are both inhibitors of HMG-CoA reductase and thus useful as antihypercholesterolemic agents, and may also serve as intermediates for preparation of other HMG-CoA reductase inhibitors. Also, in the synthesis of simvastatin by direct methylation of lovastatin, selective hydrolysis of residual lovastatin salt by treatment with Clonostachys compactiuscula ATCC 38009 or ATCC 74178 or mutants thereof or a cell-free extract derived therefrom, or a hydrolase derived therefrom yields the "triol" salt which can be easily separated from simvastatin. Excerpt(s): The present invention relates to biosynthetic production of 7[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'(S )-naphthyl]3(R),5(R)-dihydroxyheptanoic acid "triol acid" by microbiological hydrolysis of lovastatin acid, a fermentation product, using the filamentous fungus, Clonostachys compactiuscula, or a hydrolase derived therefrom. This invention also relates to the use of this process in the synthesis of simvastatin from lovastatin to facilitate the separation and isolation of simvastatin from unreacted lovastatin starting material. The triol acid and its lactone form are old compounds, i.e., ones known in the art, and they are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol biosynthesis. As inhibitors of that enzyme, they are useful as antihypercholesterolemic agents. They find further usefulness as intermediates for the preparation of other antihypercholesterolemic agents, especially those having various side chains at the 8'-position of the polyhydronaphthyl ring. For example, simvastatin, which has a 2,2-dimethylbutyryloxy side chain at the 8'-position, may be prepared using the lactone form of the triol acid as a starting material, in accordance with known procedures. The selective conversion of lovastatin salt to the triol salt would be useful in the separation of simvastatin from unreacted lovastatin in the production of simvastatin from lovastatin. Lovastatin acid has a 2-methylbutyryloxy side chain in the 8'-position and is difficult to separate from the newly formed simvastatin acid which has a 2,2-dimethyl-butyryloxy side chain at the 8'-position. Applicants have now found that selective cleavage of the 2-methylbutyryloxy side chain from lovastatin acid salt using the process of this invention employing a hydrolase enzyme from Clonostachys compactiuscula (ATCC 38009 or ATCC 74178) to yield the triol salt, results in a more easily separable mixture and greater purity of the simvastatin produced. Web site: http://www.delphion.com/details?pn=US05223415__
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Compositions comprising ONCONASE (tm) and lovastatin Inventor(s): Ardelt; Wojciech J. (New City, NY), Mikulski; Stanislaw M. (Essex Fells, NJ) Assignee(s): Alfacell Corporation (bloomfield, Nj) Patent Number: 5,595,734 Date filed: July 28, 1992 Abstract: A pharmaceutical known by the trademark ONCONASE, as described in pending commonly owned application application number 07/436,141 filed Nov. 13, 1989, is combined with two forms of another drug known as Lovastatin. The combination of ONCONASE with Lovastatin has unexpected bioactivity in vitro against ASPC-1 human pancreatic adenocarcinoma cells, A-549 human lung carcinoma cells and HT-520 human squamous cell lung carcinoma cells. Excerpt(s): The invention relates to pharmaceuticals, and more particularly relates to pharmaceuticals for use in treating cells which cause cancer tumors in humans. The above-referenced patent application discloses a pharmaceutical which will be referred to herein by the trademark ONCONASE. It has now been determined that when this pharmaceutical is used in vitro in a combined therapy with two forms of another drug, the results of the combined therapy are, in certain instances, much more bioactive than would be expected. This other drug is known as Lovastatin; the forms tested are the lactone form and the activated.beta.-hydroxyacid form. Web site: http://www.delphion.com/details?pn=US05595734__
•
Fungal strains and use thereof in antibiotic production Inventor(s): Dahiya; Jagroop S. (33-2088 Pembina Highway, Winnipeg, Manitoba, CA) Assignee(s): None Reported Patent Number: 5,362,638 Date filed: November 30, 1992 Abstract: Lovastatin is produced by a process of fermentation using a fungal transformant produced by introducing into a non-lovastatin expressing Aspergillus strain such as a strain of Aspergillus oryzae the DNA of a lovastatin-expressing strain of Aspergillus terreus. Excerpt(s): This invention relates to novel, genetically engineered fungal strains, and use thereof in preparation of antibiotics. More specifically, it relates to novel, genetically engineered strains of Aspergillus and their use in preparation of the drug lovastatin and analogs thereof. It is useful as an antihypercholesterolemic, being a potent inhibitor of HMG-CoA reductase, the rate controlling enzyme in cholesterol biosynthesis. It is a fungal metabolite produced by fermentation processes using selected fungal strains. Antibiotics such as lovastatin are metabolites which require sets of several enzymes for their synthesis. To permit their production by molecular cloning of antibiotic-producing microorganisms requires the isolation, analysis and, perhaps modification of the corresponding genes for the several enzymes. Attempts to isolate such genes from such fungal species have so far yielded clones carrying either individual genes of the set, or only incomplete gene sets - see Malpartida and Hopwood, "Molecular Cloning of the Whole Biosynthetic Pathway of a Streptomyces Antibiotic and its Expression in a Heterologous Host", Nature (1984), 309 pp 462-464.
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Web site: http://www.delphion.com/details?pn=US05362638__ •
Geranylgeraniol/lovastatin: a novel approach to blocking cancer transformation without cytotoxicity Inventor(s): McGuire; Terence F. (Pittsburgh, PA), Sebti; Said M. (Tampa, FL) Assignee(s): University of Pittsburgh (pittsburgh, Pa) Patent Number: 6,083,979 Date filed: October 9, 1996 Abstract: Method of blocking aberrant Ras signaling in a mammal while avoiding excessive cell toxicity by administration of lovastatin and geranylgeraniol. Excerpt(s): The invention relates to a method of blocking aberrant Ras signaling in a mammal while avoiding excessive cell toxicity. The mevalonic acid (MVA) pathway is responsible for the biosynthesis of cholesterol and isoprenoid intermediates such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP). Two sites in the MVA pathway have been cited to be of particular importance: the synthesis of MVA by 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an early step thought to be the major point of regulation, and the so-called "branch-point" of FPP metabolism (Brown and Goldstein 1980; Sabine, 1983; reviewed in Grunler et al., 1994). FPP is the last common intermediate in the pathway and is the substrate for a number of different enzymes that catalyze committed steps in branching pathways leading to the biosynthesis of cholesterol, ubiquinone, dolichol, as well as isoprenylated proteins and hemes. GGPP synthase, one of the branch-point enzymes, catalyzes the condensation of FPP and isopentenyl pyrophosphate to form GGPP. GGPP and FPP are utilized by geranylgeranyl-transferases (GGTases) I and II, and farnesyltransferase (FTase), respectively, for posttranslational isoprenylation of proteins on carboxyl terminal cysteine residues (reviewed in Maltese, 1990; Casey, 1992; Grunler et al., 1994). FTase and GGTase I prenylate proteins with carboxyl termini that end with a CAAX box where C=cysteine, A=aliphatic, and X=any amino acid. FTase prefers X as a serine or methionine whereas GGTase I prefers X as a leucine or isoleucine. GGTase II prenylates proteins that end in XXCC and XCX where X is any amino acid. For several proteins, isoprenylation is essential for proper intracellular localization and biological function (Holtz et al., 1989; Fukada et al. 1990; Der and Cox 1991; Hori et al. 1991; Inglese et al. 1992). In contrast to FPP, GGPP is currently known to be utilized only for protein prenylation. Geranylgeranylated proteins and farnesylated proteins appear to comprise distinct but overlapping, sets of proteins, with the former being greater in number than the latter (Farnsworth et al., 1990; Epstein et al., 1990). Many of these proteins have been shown to play essential roles in signal transduction pathways and some have been implicated in malignant transformation. For example, the geranylgeranylated low molecular weight (20-28 KDa) guanine nucleotide-binding proteins Rho and Rac have recently been shown to be critical players in regulating not only the organization of the actin cytoskeleton (Nobes and Hall 1995) but also the progression of the cell cycle through Gl (Olson et al. 1995). In addition Ras, another family of guanine nucleotidebinding proteins, control normal cell growth (Mulcahy et al., 1985) and differentiation (Bar-Sagi and Feramisco, 1985) and, when mutated, can produce malignant transformation (Reddy et al., 1982). The Ras family of proteins serve as transducers of extracellular signals from receptor tysosine kinases to the nucleus (McCormick 1993). Their stimulation by these receptors results in the activation of several growth-related pathways including a cascade of mitogen-activated protein (MAP) kinases such as Raf,
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MEK and ERK (McCormick 1993), the latter of which can translocate to the nucleus and regulate the activity of some transcription factors. In some human cancers, Ras is GTPlocked and constitutively activates the MAPK cascade. Such cancers include, but are not limited to, colorectal, pancreatic and lung carcinomas, and melanoma. Web site: http://www.delphion.com/details?pn=US06083979__ •
Hydrogenation process for the formation of 3,4-dihydro HMG-CoA reductase inhibitors Inventor(s): Schuda; Ann D. (New Providence, NJ), Shinkai; Ichiro (Westfield, NJ), Verhoeven; Thomas R. (Cranford, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 4,831,165 Date filed: September 3, 1987 Abstract: A novel hydrogenation process using a homogenous rhodium catalyst for selectively reducing the 3,4 double bond in the polyhydronaphthyl ring of lovastatin, simvastatin or C-8-acyl or C-6-substituted analogs thereof is disclosed. Excerpt(s): R.sub.5 is H or CH.sub.2 OH or CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9; provided that at least one of R.sub.4 or R.sub.5 is H. a is a double bond or a single bond. The instant process selectively reduces the 3,4 double bond in the polyhydronaphthyl ring of lovastatin, simvastatin or 8-acyl or 6-substituted analogs thereof. A homogenous rhodium catalyst is able to discriminate between a double bond in the 3,4 and 4a,5 positions, complexing with and thus allowing hydrogenation of only the 3,4 double bond. Critical to the present invention is applicants' finding that an alcoholic co-solvent increases the catalyst lifetime which thus removes the necessity of large excesses of the expensive rhodium catalyst. The present reaction is typically conducted with a 5 weight percent of catalyst to olefinic substrate which contrasts with the very large excesses of catalyst required in the prior art reductions. Unexpectedly, inclusion of an alcoholic cosolvent also decreases substantially the amount of the "1,4-reduction" side product (e.g. II) which is produced. Formation of large proportions of this 3,5-dihydro side product is highly detrimental and seriously compromises the final product purity since it can cocrystallize with the desired product. This side product has previously been removed by a tedious HPLC procedure. Web site: http://www.delphion.com/details?pn=US04831165__
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Hydrogenation process for the formation of 3,5-dihydro HMG-CoA reductase inhibitors Inventor(s): DeCamp; Ann E. (New Providence, NJ), Shinkai; Ichiro (Westfield, NJ), Verhoeven; Thomas R. (Cranford, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 4,826,999 Date filed: September 3, 1987 Abstract: A novel hydrogenation process, using a homogenous iridium or rhodium catalyst for selectively adding hydrogen to the 3,5 positions in the polyhydronaphthyl
Patents 63
ring of lovastatin, simvastatin or C-8-acyl or C-6-substituted analogs thereof, is disclosed. Excerpt(s): (h) phenyloxycarbonyl. R.sub.5 is H or CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9 or OSi(Me).sub.2 t-C.sub.4 H.sub.9; provided that when either R.sub.4 or R.sub.5 is CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9 the other is H; and one and only one of R.sub.4 and R.sub.5 can be OSi(Me).sub.2 t-C.sub.4 H.sub.9. provided that at least one of R.sub.4 or R.sub.5 is H. Web site: http://www.delphion.com/details?pn=US04826999__ •
Hydrogenation process for the formation of 4A,5-dihydro HMG-CoA reductase inhibitors Inventor(s): Schuda; Ann D. (New Providence, NJ), Shinkai; Ichiro (Westfield, NJ), Verhoeven; Thomas R. (Cranford, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 4,876,364 Date filed: September 3, 1987 Abstract: A novel hydrogenation process, employing an iridium or rhodium catalyst, in an alcoholic solvent mixture, for the reduction of the 4a,5 double bond in the polyhydronaphthyl ring of des-(.alpha.-methylbutyryl)-8-hydroxy-lovastatin or analogs thereof, is disclosed. Excerpt(s): Kuo et al. (U.S. Pat. No. 4,490,546 and J. Org. Chem. 48, 1991 (1983)) have disclosed a process for hydrogenating the 4a,5 double bond of lovastatin. However this process requires 5 separate steps leading to the natural trans isomer in about 10 percent yield. Moreover the desired product is contaminated with the cis-fused dihydro derivative. The use of a ligating group, such as OH, on an olefinic substrate is known to direct the attack of a hydrogenation catalyst such as [Ir(COD)PCy.sub.3 (pyr)]PF.sub.6 from the face of the moleule containing the directing group. However, there are no reports of selective hydrogenation of a conjugated diene, with catalysts of this type. R.sub.2 is H or CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9 or OSi(Me).sub.2 t--C.sub.4 H.sub.9; provided that when R.sub.1 or R.sub.2 is CH.sub.2 OSi(Me).sub.2 t--C.sub.4 H.sub.9 the other is H; and one and only one of R.sub.1 and R.sub.2 can be OSi(Me).sub.2 t--C.sub.4 H.sub.9. Web site: http://www.delphion.com/details?pn=US04876364__
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Intermediates and processes for 6-carboxy HMG-CoA reductase inhibitors Inventor(s): Hoffman; William F. (Lansdale, PA), Lee; Ta J. (Lansdale, PA) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 4,841,074 Date filed: December 11, 1987 Abstract: This invention discloses intermediates and a process for the preparation of 6desmethyl-6-carboxy derivatives of lovastatin and analogs thereof at the 9-acyl side chain.
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Excerpt(s): Hypercholesterolemia is known to be one of the prime risk factors for ischemic cardiovascular disease, such as arteriosclerosis. Bile acid sequestrants have been used to treat this condition; they seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable. Mevacor (lovastatin), now commercially available, is one of a group of very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. In addition to the natural fermentation products, mevastatin and lovastatin, there are a variety of semi-synthetic and totally synthetic analogs thereof. These compounds are prepared by the action of certain microorganisms on the corresponding non-hydroxylated substrates. One such organism described in U.S. Pat. No. 4,537,859 is of the genus Nocardia. Web site: http://www.delphion.com/details?pn=US04841074__ •
Metabolic controlled fermentation procedure for the manufacture of lovastatin hydroxy acid Inventor(s): Balogh; Gabor (Debrecen, HU), Cseke; Laszlo (Debrecen, HU), Olah; Antal (Debrecen, HU), Seress; Peter (Debrecen, HU) Assignee(s): Biogal Gyogyszergyar Rt. (debrecen, Hu) Patent Number: 6,500,651 Date filed: April 5, 2000 Abstract: A method for producing mevinolin by a microorganism in a fermentation process having a seed culture stage and a main fermentation stage, includinga) cultivating a microorganism biomass in the seed culture stage to produce an inoculum;b) transferring the inoculum into a fermentation medium in the main fermentation stage; and,c) maintaining steady stage conditions in the main fermentation stage, thereby producing a fermentation broth containing mevinolin. Preferably, the steady state conditions are maintained in the main fermentation stage by one or more of feeding of organic carbon sources; controlling glucose and/or total reducing sugar content; feeding of organic nitrogen sources; controlling pH; controlling foam level; controlling the mass of the fermentation broth by withdrawals and feedings; and, controlling the dissolved oxygen level. Excerpt(s): This invention relates generally to the biosynthesis of cholesterol reducing agents. More specifically, the invention relates to the biosynthesis of the cholesterol lowering agent mevinolin by certain microorganisms. Mevinolin (lovastatin; monacolin K;.beta.,.delta.-dihydroxy-7-[1,2,6,7,8,8a-hexahydro-2,6-dimethyl-8-(2-methy lbutyryloxy)-naphtalen-1-yl]-heptanoic acid.delta.-lactone) is one of the most important known cholesterol lowering agents. Mevinolin, as used herein, includes both the lactone and free hydroxy acid forms. Its open hydroxy acid form is a potent inhibitor of the 3hydroxy-3-methyl-glutarylcoenzyme A reductase enzyme, which catalyses the formation of mevalonic acid, an early intermediate of cholesterol biosynthesis. Mevinolin is specifically advantageous because, as a result of its application, biosynthetic intermediates with a toxic steroid skeleton, formed at a later stage of biosynthesis fail to accumulate. Mevinolin increases the number of LDL-receptors at the surface of the cell membrane which remove the LDL cholesterol circulating in the blood, thereby inducing the lowering of blood plasma cholesterol level. Web site: http://www.delphion.com/details?pn=US06500651__
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Method for alkylating the alpha carbon of the 2-methylbutyrate secondary chain of lovastatin Inventor(s): Galeazzi; Edvige (Mexico City, MX), Garcia; Gustavo A. (Mexico City, MX), Lara; Fernando (Cuernavaca, MX), Lopez; Gema (Mexico City, MX), Martinez; Orestes (Mexico City, MX), Tisselli; Eugenio (Mexico City, MX), Trejo; Alicia (Mexico City, MX) Assignee(s): Fermic S.a. DE C.v. (mexico City, Mx) Patent Number: 6,472,542 Date filed: November 29, 2001 Abstract: Simvastatin is produced from lovastatin in high yield and in pharmaceutical purity by forming an amide of lovastatin and protecting the free hydroxyl groups of the lovastatin amide with hexamethyidisilazane (HMDS) to form a protected lovastatin amide. The.alpha.-carbon of the 2-methylbutyrate secondary chain of the protected lovastatin amide may be methylated to form a protected simvastatin amide. The protecting groups may be removed therefrom by quenching the methylation reaction with water. The simvastatin amide which is obtained may be hydrolyzed to form simvastatin acid, followed by forming a simvastatin ammonium salt, lactonizing the salt to form simvastatin, and recrystallizing the thus formed crude Simvastatin to a high degree of purity. The HMDS protecting agent for the lactone hydroxyl groups of Lovastatin is selected so as to result in a reaction that does not produce acid so that a base, such as imidazole, is not required to neutralize the acidity of the reaction medium. Another advantage of using HMDS as a protecting agent is that the removal of the protecting agent after the methylation reaction is carried out simply, for example, by water quenching. The lactonization reaction of the present invention may be carried out using a low boiling point solvent, such as methylene chloride, in the presence of inorganic acids such as sulfuric, hydrochloric, methanesulfonic or phosphoric acid as catalyst. Excerpt(s): The present invention relates to a novel process for alkylating the alpha carbon of the 2-methylbutyrate secondary chain of lovastatin and intermediate products of the novel process, wherein the process gives a product in a high yield and in pharmaceutical purity. In recent years, cardiopathy has increasingly become a medical problem. This problem is associated with several factors such as diet, stress and the sedentary lifestyle of the population. One of the most important risk factors associated with coronary heart disease is the incidence of elevated cholesterol levels in plasma. Elevated cholesterol levels in plasma may cause, among other things, obstruction in the arteries and circulatory problems. See Reynolds, J. Martindale, (1993), The Extra Pharmacopoeia, 30.sup.th Edition, The Pharmaceutical Press. Cholesterol accumulation is due to both exogenous factors, such as diet, and endogenous factors, such as cholesterol production by the organism. Presently, unlike exogenous factors, cholesterol production by the organism can only be controlled by drugs that inhibit cholesterol biosynthesis. Compounds represented by structure (II) have been obtained by various routes, such as those described in U.S. Pat. Nos. 4,820,850, to Verhoeven et al., 6,271,398 B1, to Van Dalen F. et. al. and 6,294,680 B1, to Vries et al., and in European Patent No. 299,656 B1, to Verhoeven et al., wherein: (1) the lactone is hydrolyzed, (2) the OH groups of the lactone are protected, (3) the 2-methylbutyrate chain is methylated to form the 2,2dimethylbutyrate chain, and (4) protection is removed from the lactone OH groups. However, this route is very time and labor intensive and it gives very low product yields. Web site: http://www.delphion.com/details?pn=US06472542__
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Method of preventing or treating statin-induced toxic effects using L-carnitine or an alkanoyl L-carnitine Inventor(s): Arduini; Arduino (Rome, IT), Carminati; Paolo (Milan, IT), Peschechera; Alessandro (Ostia Lido, IT) Assignee(s): Sigma-tau (rome, It) Patent Number: 6,245,800 Date filed: September 1, 1999 Abstract: A pharmaceutical composition is described, comprising a lipid-lowering drug such as lovastatin, simvastatin, pravastatin and fluvastatin and L-carnitine or an alkanoyl L-carnitine, which, while conserving the efficacy of the lipid-lowering drug, is substantially devoid of the toxic or side effects typical of such drugs. Excerpt(s): The invention described herein relates to a pharmaceutical composition for the treatment of diseases caused by lipid metabolism disorders, and in particular a pharmaceutical composition comprising a statin and L-carnitine or one of its alkanoyl derivatives, useful for the prevention and treatment of statin-induced toxic or side effects. Cardiovascular diseases related to lipid metabolism disorders are very frequent in the industrialised countries. In Italy, for instance, they account for more than 40% of the overall mortality (Capocaccia R., Farchi G., Prati S. et al.: La mortalita' in Italia nell'anno 1989. Rapporto ISTISAN 1992/22). Our knowledge of the relationships between cholesterol and coronary heart disease stems from epidemiological studies conducted in recent years. The conclusions of these studies indicate that the development of severe coronary atherosclerosis is closely related to serum cholesterol levels (McGill H. C. Jr. et al.: The International Atherosclerosis Project. Lab. Invest. 18: 463-653, 1968; Keys A.: Seven Countries: Death and Coronary Heart Disease. Harvard University Press, Cambridge, 1980). Correction of eating habits through an appropriate diet is always the first measure to be adopted in cases of hyperlipidaemia. Good results, however, are not always achieved owing to widespread intolerance of the strict dietary regimen, to the severity of the hypercholesterolaemia or to genetic-type resistance. Web site: http://www.delphion.com/details?pn=US06245800__
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Methods of treating nitric oxide and cytokine mediated disorders Inventor(s): Singh; Inderjit (Mount Pleasant, SC) Assignee(s): Medical University of South Carolina (charleston, Sc), Musc Foundation for Research Development (charleston, Sc) Patent Number: 6,511,800 Date filed: May 25, 2000 Abstract: The current invention discloses novel methods for the inhibition of inducible nitric oxide synthesis (iNOS) and the production of NO. Methods of inhibiting the induction of proinflammatory cytokines are also described. Methods of treating various disease states, such as X-linked adrenoleukodystrophy, multiple sclerosis, Alzheimer's and septic shock using inhibitors of iNOS and cytokine induction are disclosed. The inhibitors include the exemplary compounds lovastatin, a sodium salt of phenylacetic acid (NaPA), FPT inhibitor II, N-acetyl cysteine (NAC), and cAMP. Methods of treating a nitric oxide or cytokine mediated disorder in a cell comprising administering a
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biologically effective amount of at least one induction suppressor of an inducible nitric oxide synthase or a cytokine is also described. Excerpt(s): The present invention relates generally to the treatment of conditions involving undesired or pathological levels of inducible nitric oxide synthase (iNOS), e.g. septic shock or neuroinflammatory diseases. In one important aspect, the invention relates to methods of suppressing, inhibiting or preventing the accumulation of nitricoxide induced cytotoxicity by using inhibitors that block or suppress the induction of cytokines and/or inducible nitric oxide synthase. Another aspect of the invention is the treatment of conditions involving undesired or pathological levels of proinflammatory cytokines (i.e. TNF-.alpha., IL-1.beta., IL-2, IL-6, IL-8 and/or IFN-.gamma.) and/or iNOS. One important aspect of the invention relates to methods of suppressing, inhibiting, or preventing proinflammatory cytokines and/or iNOS induced or aggravated disorders including conditions involving the detrimental effects of inflammation (e.g. disorders such as lupus, rheumatoid arthritis, osteoarthritis, amyotrophic lateral sclerosis, and autoimmune disorders; ischemia/reperfusion; neuroinflammatory conditions such as Alzheimer's, stroke, multiple sclerosis, X-linked adrenoleukodystrophy; and the effects of aging). Nitric oxide (NO) is a potent pleiotropic mediator of physiological processes such as smooth muscle relaxation, neuronal signaling, inhibition of platelet aggregation and regulation of cell mediated toxicity. It is a diffusible free radical which plays many roles as an effector molecule in diverse biological systems including neuronal messenger, vasodilation and antimicrobial and antitumor activities (Nathan, 1992; Jaffrey et al., 1995). NO appears to have both neurotoxic and neuroprotective effects and may have a role in the pathogenesis of stroke and other neurodegenerative diseases and in demyelinating conditions (e.g., multiple sclerosis, experimental allergic encephalopathy, Xadrenoleukodystrophy) and in ischemia and traumatic injuries associated with infiltrating macrophages and the production of proinflamatory cytokines (Mitrovic et al., 1994; Bo et al., 1994; Merrill et al., 1993; Dawson et al., 1991, Kopranski et al., 1993; Bonfoco et al., 1995). A number of pro-inflammatory cytokines and endotoxin (bacterial lipopolysaccharide, LPS) also induce the expression of iNOS in a number of cells, including macrophages, vascular smooth muscle cells, epithelial cells, fibroblasts, glial cells, cardiac myocytes as well as vascular and non-vascular smooth muscle cells. Although monocytes/macrophages are the primary source of iNOS in inflammation, LPS and other cytokines induce a similar response in astrocytes and microglia (Hu et al., 1995; Galea et al., 1992). During inflammation, reactive oxygen species (ROS) are generated by various cells including activated phagocytic leukocytes; for example, during the neutrophil "respiratory burst", superoxide anion is generated by the membrane-bound NADPH oxidase. ROS are also believed to accumulate when tissues are subjected to inflammatory conditions including ischemia followed by reperfusion. Superoxide is also produced under physiological conditions and is kept in check by superoxide dismutates. Excessively produced superoxide overwhelms the antioxidant capacity of the cell and reacts with NO to form peroxynitrite, ONOO.sup.-, which may decay and give rise to hydroxyl radicals,.sup.- OH (Marietta, M., 1989; Moncada et al., 1989; Saran et al., 1990; Beckman et al. 1990). NO, peroxynitrite and OH are potentially toxic molecules to cells including neurons and oligodendrocytes that may mediate toxicity through modification of biomolecules including the formation of iron-NO complexes of iron containing enzyme systems (Drapier et al., 1988), oxidation of protein sulfhydryl groups (Radi et al., 1991), nitration of proteins and nitrosylation of nucleic acids and DNA strand breaks (Wink et al., 1991). Web site: http://www.delphion.com/details?pn=US06511800__
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Mutant strains of Aspergillus terreus for producing 7-[1,2,6,7,8,8a(R)-hexa-hydro2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-napht hyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid),I) Inventor(s): Cover; William H. (Lansdale, PA), Dabora; Rebecca L. (Andover, MA), Hong; Anderson (Taipei, TW), Reeves; Christopher (Mill Creek, WA), Stieber; Robert W. (Harrisonburg, VA), Vinci; Victor A. (Charlottesville, VA) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 5,250,435 Date filed: June 4, 1991 Abstract: Novel strains of Aspergillus terreus have been discovered which provide fermentation production of at least 5.2 g/L of 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)dimethyl-8(S)-hydroxy-1(S)-naphthyl ]-3(R),5(R)-dihydroxyheptanoic acid (triol acid, I), but with production of not more than 0.85 g/L of (triol acid)-related side products and specifically less than 0.10 mg/liter of lovastatin. The predominant fermentation product triol acid, may be converted in a straightforward manner to its lactone form, in which it is an inhibitor of HMG-CoA reductase and thus useful as an antihypercholesterolemic agent, and in which it may also serve as an intermediate for preparation of other HMGCoA reductase inhibitors. Excerpt(s): The present invention relates to strains of Aspergillus terreus useful in a novel fermentation process for the production of at least 5.2 g/L of 7-[1,2,6,7,8,8a(R)hexahydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl ]-3(R),5(R)dihydroxyheptanoic acid (troil acid, I) by mutant strains of Aspergillus terreus, with production of 0.85 g/L or less of triol acid-related side products, as those are defined further below and less than 0.10 mg/liter of lovastatin. Triol acid (I) is an inhibitor of 3hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol biosynthesis. As an inhibitor of that enzyme, the triol acid is useful as an antihypercholesterolemic agent. It finds further usefulness as an intermediate for the preparation of other antihypercholesterolemic agents, especially those having various side chains at the 8-position of the polyhydronaphthyl ring. For example, simvastatin, which has a 2,2-dimethylbutyryloxy side chain at that position, may be prepared using the lactone form of the triol acid as a starting material, in accordance with procedures described in U.S. Pat. No. 4,444,784. The present invention specifically relates to the strain MF-5544 of Aspergillus terreus, ATCC 74064 and to mutant strains thereof which are capable of producing at least 5.2 g/L of triol acid (I) and not more than 0.85 g/L of (triol acid)-related side products and less than 0.10 mg/liter of lovastatin. Web site: http://www.delphion.com/details?pn=US05250435__
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Nitrogen feed in statin fermentation Inventor(s): Lindsay; Jennifer May (Voorburg, NL), Ykema; Adriaantje (Leiden, NL) Assignee(s): Dsm N.v. (nl) Patent Number: 6,165,757 Date filed: September 15, 1999 Abstract: A fermentation process is disclosed for producing an HMG-CoA reductase inhibitor such as lovastatin or compactin. In particular, it relates to a process wherein at
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least part of the assimilable nitrogen source and, optionally, the carbon source is provided continuously or intermittently to the culture. Excerpt(s): The present invention relates to a fermentation process for the production by microorganisms of compounds which are HMG-CoA reductase inhibitors, such as lovastatin and compactin. In particular, it relates to a process where an assimilable source of nitrogen or nitrogen and carbon is provided continuously or intermittently. A wide variety of relatively complex molecules, in particular drugs, can be produced by microorganisms during a fermentation process. Usually, the microorganism is fed with various assimilable sources of the elements required for the organism to produce the desired product. The efficiency of production depends on a large number of factors, not least the nature of the carbon sources and the further conditions of fermentation. U.S. Pat. No. 4,231,938 (Merck) describes the cultivation of an Aspergillus microorganism in order to produce lovastatin. Web site: http://www.delphion.com/details?pn=US06165757__ •
Process for manufacturing simvastatin and the novel intermediates Inventor(s): Acharya; Poornaprajna (Bangalore, IN), Mathew; Joy (Bangalore, IN), Sambasivam; Ganesh (Bangalore, IN), Sridharan; Madhavan (Bangalore, IN) Assignee(s): Biocon India Limited (bangalore District, In) Patent Number: 6,573,392 Date filed: May 10, 2002 Abstract: This invention describes the synthesis of simvastatin from lovastatin by converting the lovastatin to lova amide using a secondary amine and subsequent reaction with a metal amide base generated from n-butyl lithium and pyrrolidine and followed by treatment with methyl iodide to give desired C-methylated intermediate. This intermediate was further transformed to the final product, simvastatin. This method of production consumes lesser quantities of metal amide, gives fewer side reactions and a lowered overall cost of manufacture of simvastatin than other procedures reported. Excerpt(s): The naturally occurring compounds of formula I and their semi-synthetic analogs are very active antihypercholesterolemic agents that function by limiting the cholesterol biosynthesis by inhibiting the HMG-CoA reductase enzyme. Compounds of formula Ia, shown in page 9, include the natural fermentation products like mevinolin (disclosed in U.S. Pat No. 4,231,938 and also known as lovastatin), compactin (disclosed in U.S. Pat No. 3,983,240) and a variety of semi-synthetic and totally synthetic analogs thereof, all having the natural 2-methylbutyrate side chain. Compounds of formula IIa, shown in page 9, having a 2,2-dimethylbutyrate side chain (e.g., simvastatin) are known to be more active inhibitors of HMG-CoA reductase than their 2-methylbutyate analogs and thus of greater utility in the treatment of artherosclerosis, hyperlipemia, familial hypercholesterolemia and similar disorders. Web site: http://www.delphion.com/details?pn=US06573392__
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Process for manufacturing simvastatin from lovastatin or mevinolinic acid Inventor(s): Khanna; Jag Mohan (New Delhi, IN), Kumar; S. M. Dileep (New Delhi, IN), Kumar; Yatendra (Haryana, IN), Misra; Satyananda (New Delhi, IN), Thaper; Rajesh Kumar (Haryana, IN) Assignee(s): Ranbaxy Laboratories, Ltd. (new Delhi, In) Patent Number: 5,763,646 Date filed: March 13, 1997 Abstract: A process for preparing simvastatin from lovastatin or mevinolinic acid in salt form comprises treating either starting material with cyclopropyl or butyl amine, the pyranone ring thereby being opened when lovastatin is the starting material, adding a methyl group to the 2-methylbutyrate side chain, and thereafter closing the open pyranone ring to produce simvastatin. The process is performed without protecting and deprotecting the two hydroxy groups of the open pyranone ring. In a preferred embodiment, the starting material is treated with cyclopropyl amine which produces simvastatin via the novel intermediate lovastatin cyclopropyl amide. Excerpt(s): This patent application is related to a patent application entitled "KEY INTERMEDIATES IN THE MANUFACTURE OF SIMVASTATIN" assigned Ser. No. 08/816,574, and filed on Mar. 13, 1997. Compounds of structure I include the natural fermentation products mevinolin (structure Ia where R.dbd.CH.sub.3, disclosed in U.S. Pat. No. 4,231,938, and also known as lovastatin), compactin (structure Ib where R.dbd.H, disclosed in U.S. Pat. No. 3,983,140), and a variety of semi-synthetic and totally synthetic analogs thereof, all having the natural 2-methylbutyrate side chain. The recent introduction into the market of simvastatin (IIa), a more potent HMG-CoA reductase inhibitor than lovastatin (Ia), has provided a need for a high yielding process which is more economically efficient and environmentally sound than those disclosed in the prior art. Web site: http://www.delphion.com/details?pn=US05763646__
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Process for the formation of 6-desmethyl-6-exo-methylene derivatives of lovastatin and analogs thereof Inventor(s): Shinkai; Ichiro (Westfield, NJ), Thompson; Andrew S. (Mountainside, NJ), Verhoeven; Thomas R. (Cranford, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 4,866,186 Date filed: June 30, 1988 Abstract: A process and intermediates in preparation of 6-exomethylene derivatives of lovastatin and 8-acyl and di- and tetrahydro analogs thereof is disclosed. Excerpt(s): Hypercholesterolemia is known to be one of the prime risk factors for ischemic cardiovascular disease, such as arteriosclerosis. Bile acid sequestrants have been used to treat this condition; they seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable. R' is hydrogen, C.sub.1-5 alkyl, or C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino. It would be very useful to be able to prepare such 6-exomethylene derivatives in a synthetic scheme from available starting materials.
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Process for the preparation of simvastatin and analogs thereof Inventor(s): Zlicar; Marco (Celje, SI) Assignee(s): Lek Pharmaceutical and Chemical Company D.d. (ljubljana, Si) Patent Number: 6,384,238 Date filed: May 31, 2001 Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis for example simvastatin. This invention relates to the novel method for the acylation of sterically hindered alcohols which is applicable in the process for the preparation of simvastatin and derivatives thereof. Excerpt(s): Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, some are obtained by treating the fermentation products using the methods of chemical synthesis (simvastatin) or they are the products of total chemical synthesis. In the literature several processes for the preparation of simvastatin are known which are mainly based on one of the two following basic principles. A process of direct methylation of the 2-(S)methylbutyryloxy side chain of lovastatin is disclosed in U.S. Pat. No. 4,582,915. That process is based on direct methylation of the 2-(S)-methylbutyryloxy side chain of lovastatin using a methyl alkyl amide and a methyl halide in a single step. The described process has certain disadvantages: the low level of conversion in the Cmethylation step, low temperatures (-70 to -15.degree. C.) required for the reaction to be carried out and a number of undesired side reactions of methylation occurring at other sites of the molecule as well as using of butyl lithium which produces an explosive reaction with water and is highly pyrogen at higher concentrations. With minor modifications the yields in the methylation step may be improved, however, the total yields remain relatively low. U.S. Pat. No. 4,820,850 discloses a process for methylation of the 2-(S)-methylbutyrylox side chain of lovastatin using a single charge of amide base and alkyl halide. The process disclosed therein involves six steps; despite the fact that the level of conversion is high in the methylation step, the process is not economical. Web site: http://www.delphion.com/details?pn=US06384238__
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Process for the production of lovastatin using Coniothyrium fuckelii Inventor(s): Gerson; Donald F. (Winnipeg, CA), Xiao; Xinfa (Winnipeg, CA) Assignee(s): Apotex, Inc. (ontario, Ca) Patent Number: 5,409,820 Date filed: August 6, 1993
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Abstract: A novel microorganism, Coniothyrium fuckelii ATCC 74227, and a process of using the microorganism for the production of lovastatin comprising fermenting Coniothyrium fuckelii ATCC 74227 or a lovastatin-producing mutant thereof in a nutrient medium containing assimilable sources of carbon, nitrogen, and inorganic salts under aerobic fermentation conditions. Excerpt(s): The present invention relates to a process for preparing hypocholesteremic products, e.g., Lovastatin and Mevastatin. High blood cholesterol levels are recognized as being one of the main causes of cardiopathy, e.g., cardiac infarction, arteriosclerosis or hyperlipaemia. It is currently believed that a causative factor in such diseases is the deposition of cholesterol in the body, particularly within the arteries. As a result, considerable research has been undertaken with a view to discovering physiologically acceptable substances which are capable of inhibiting cholesterol biosynthesis and thus are capable of reducing blood cholesterol levels. Several patents have issued directed to such compounds and their process for production. Web site: http://www.delphion.com/details?pn=US05409820__ •
Process for the production of semi synthetic statins via novel intermediates Inventor(s): Faber; Wijnand Sjourd (Groningen, NL), Kalkman-Agayn; Venetka Ivanova (Den Haag, NL), Sibeyn; Mieke Ivanova (Amersfoort, NL), Vries; Ton Rene (Groningen, NL), Wijnberg; Hans (Groningen, NL) Assignee(s): Plus Chemicals, B.v. (mijdrecht, Nl) Patent Number: 6,294,680 Date filed: January 5, 2000 Abstract: A process has been provided to produce semi synthetic statins, as for instance simvastatin with a high yield, for another statin, preferably a naturally occurring statin, as for instance lovastatin. Also a number of novel intermediate compounds, prepared during said process, has been provided. Excerpt(s): The present invention relates to a process for preparing semi-synthetic statins and to intermediates formed during said process. It is well known that certain mevalonate derivatives are active as hypercholesterolemic agents, which function by limiting cholesterol biosynthesis by inhibiting the enzyme HMG-CoA reductase. These mevalonate derivatives are the naturally occurring fungal metabolites lovastatin and compactin. Semi-synthetic and synthetic analogs thereof are also active. The naturally occurring compounds lovastatin and compactin posess a 2-methylbutyrate side chain at the 8-position of the hexahydronaphthalene ring system. Analogs with a 2,2dimethylbutyrate moiety at this position, such as simvastatin, appear to be more effective inhibitors of HMG-CoA reductase. Web site: http://www.delphion.com/details?pn=US06294680__
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Process to manufacture simvastatin and intermediates Inventor(s): Doucette; Gary (Downsview, CA), Karimian; Khashayar (Mississauga, CA), Li; Yiwei (Etobicoke, CA), Tam; Tim Fat (Woodbridge, CA), Tao; Yong (Brampton, CA) Assignee(s): Apotex Inc. (weston, Ca) Patent Number: 6,506,929 Date filed: April 24, 2001 Abstract: A process is disclosed for the preparation of simvastatin which enables highly regio selective C-methylation of the 2'-position group of lovastatin without requiring protection/deprotection of 13-OH of lovastatin and lactone ring opening/closure. Excerpt(s): Simvastatin is an antihypercholesterolemic agents which inhibits cholesterol biosynthesis by inhibiting the enzyme HMG-Co A reductase. Animal and clinical data suggest simvastatin is twice as potent as lovastatin. The pharmacology and clinical use of simvastatin has been reviewed (V. E. Mauro, J. L. MacDonald, DICP, The Annuals of Pharmacotherapy, 1991, 25, 257). The synthesis of simvastatin and related compounds was reviewed by Y. Chapleur in Recent Prog. Chem. Synth. Antibiot. Relat. Mircob. Product, 1993, p.829-937; editor: Lukacs, Gabor; publisher: Springer, Berlin, Germany. The overall yield is less than 40%. Variations of his method are disclosed in U.S. Pat. Nos. 5,159,104, 4,450,171, and 4,444,784. The process is laborious and affords simvastatin only moderate yields. Furthermore, from the teachings of a subsequent U.S. Pat. No. 4,820,850 at column 1, lines 53 to 68 to column 2, lines 1 to 20 and its corresponding Canadian patent 1,287,063 at page 3, this process appears to have numerous disadvantages. Web site: http://www.delphion.com/details?pn=US06506929__
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Treatment of arteriosclerosis and xanthoma Inventor(s): Horikoshi; Hiroyoshi (Kobe, JP), Ito; Takashi (Kobe, JP), Tsujita; Yoshio (Tokyo, JP) Assignee(s): Sankyo Company, Limited (tokyo, Jp) Patent Number: 5,798,375 Date filed: July 2, 1996 Abstract: A combination of one or more HMG-CoA reductase inhibitors (for example pravastatin, lovastatin, simvastatin, fluvastatin, rivastatin or atorvastatin) with one or more insulin sensitizers (for example troglitazone, pioglitazone, englitazone, BRL-49653, 5-(4-{2-›1-(4-2'-pyridylphenyl)ethylideneaminooxy!-ethoxy}benzyl)thiazolid ine-2,4dione, 5-{4-(5-methoxy-3-methylimidazo›5,4-b!pyridin-2-yl-methoxy)benzyl}thiazoli dine-2,4-dione or its hydrochloride, 5-›4-(6-methoxy-l-methylbenzimidazol-2ylmethoxy)benzyl!thiazolidine-2,4-d ione, 5-›4-(l-methylbenzimidazol-2ylmethoxy)benzyl!-thiazolidine-2,4-dione and 5-›4-(5-hydroxy-1,4,6,7tetramethylbenzimidazol-2-ylmethoxy) benzyllthiazolidine-2,4-dione) exhibits a synergistic effect and is significantly better at preventing and/or treating arteriosclerosis and/or xanthoma than is either of the components of the combination alone. Excerpt(s): The present invention relates to methods and compositions for the treatment and prophylaxis of arteriosclerosis and/or xanthoma. Throughout the world, in recent years, the tendency has been for the incidence of coronary artery disease and arteriosclerosis, including atherosclerosis, to increase, even in those countries in which
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hitherto they have not been prevalent. Amongst the factors implicated in such an increase are changes in lifestyle, including the "Western" meat-rich diet, and the adoption of such a diet even in countries where it is not traditional, and the general increase in the average age of the population. As a result, these diseases and arteriosclerosis, in particular, are widely feared as arteriosclerosis is a well known potential cause of unexpected death, for example by such sequelae of arteriosclerosis as myocardial infarction. One of the main risk factors implicated in these diseases is a high blood plasma lipid level, particularly a high blood plasma cholesterol level. There have, therefore, been many attempts to use an agent which lowers the cholesterol level in order to prevent and cure these diseases, and many compounds have been developed which, to a greater or lesser extent, have this effect. For example, one such compound, which has been very successful and is very well known is pravastatin, which is a lipid regulating agent and is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (hereinafter referred to as "HMG-CoA reductase inhibitor") which is believed to act on the rate-determining step of cholesterol biosynthesis. It has been reported that coronary arteriosclerosis and xanthoma may be prevented in rabbits receiving pravastatin, but its efficacy remains insufficient ›Biochimica et Biophysica Acta, 960, 294302 (1988)!. Studies to control coronary arteriosclerosis and xanthoma have been carried out using a combination of two lipid regulating agents, pravastatin and cholestyramine, which is well known as an agent for lowering lipoprotein levels, but the efficacy of this combination also remains insufficient ›Atherosclerosis, 83, 69-80 (1990)!. Web site: http://www.delphion.com/details?pn=US05798375__ •
Use of coenzyme Q.sub.10 in combination with HMG-CoA reductase inhibitor therapies Inventor(s): Folkers; Karl A. (Austin, TX), Langsjoen; Per H. (Temple, TX), Willis; Richard A. (Austin, TX) Assignee(s): Karl Folkers Foundation for Biomedical and Clinical Research (austin, Tx) Patent Number: 5,316,765 Date filed: September 19, 1991 Abstract: Disclosed are methods for inhibiting the side effects attendant treatment with HMG-CoA reductase inhibitors. Treatment of a patient with and HMG-CoA reductase inhibitor in combination with coenzyme Q.sub.10 provides a reduction in patient cholesterol levels and guards against typical HMG-CoA reductase-inhibitor side effects, most notably liver dysfunction and cardiac dysfunction. The combination of lovastatin, an HMG-CoA reductase inhibitor, and coenzyme Q.sub.10 in ratios of between 1:2 to 1:29 provide significant enhancement of a patient's caridac condition. By way of example, other HMG-CoA reductase inhibitors which may be included in the claimed combinations include pravastatin, compactin, fluvastatin, dalvastatin, simvastatin, BMY 22089, GR-95030, HR-780, CI-981, SQ 33,600, and BMY 22566 and XU-62-320. Excerpt(s): The field of the present invention relates to methods and compositions for reducing side effects HMG-CoA reductase inhibitor therapy particularly those related to the physiologically depressed levels of coenzyme Q.sub.10 in the animal. Most particularly, the invention provides methods effective for the reduction of cholesterol using an HMG-CoA reductase inhibitor, while reducing and/or inhibiting the side effects clinically linked to the use of HMG-CoA reductase inhibitors, such as liver dysfunction, musculoskeletal, nervous system/psychiatric, cardiac dysfunction, skin and special senses disorders. The invention also provides specifically defined
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formulations which include a mixture of an HMG-CoA reductase inhibitor and coenzyme Q.sub.10. Coronary artery disease is the major cause of death in Western countries. Hypercholesterolemia is known to be a primary risk factor for death from coronary artery disease. It is known that 50% or more of the total body cholesterol in humans is derived from intrinsic biosynthesis. It is also known that a rate-limiting step of major significance in the biosynthesis of cholesterol is at the level of the enzyme known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase or HMG-CoA reductase. This enzyme then was logical for inhibition to reduce the intrinsic biosynthesis of cholesterol toward reducing the risk factor of hypercholesterolemia and coronary artery death. Alberts et al. described the isolation, structure and biochemical properties of an active inhibitor of HGMCoA reductase which they named mevinolin. The scientific name, mevinolin, introduced in 1980, corresponds to the subsequent trademark name, MEVACOR.RTM. This chemical substance is 1,2,6,7,8,8a-hexahydro-.beta.,.delta.dihydroxy-2,6-dimethyl-8-(2-methyl-1 -oxobutoxy)-1-naphthaleneheptanoic acid.delta.lactone. Web site: http://www.delphion.com/details?pn=US05316765__ •
Use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a reductase as a modality in cancer therapy Inventor(s): Kang; Won Ki (Rockville, MD), Myers; Charles (Rockville, MD), Neckers; Len (Bethesda, MD), Trepel; Jane (Bethesda, MD), Whitesell; Luke (Bethesda, MD) Assignee(s): The United States of America AS Represented by the Secretary of the (washington, Dc) Patent Number: 6,040,334 Date filed: October 20, 1994 Abstract: Methods of treating various cancers, such as prostatic adenocarcinoma, with inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG Co-A), such as lovastatin, are provided. Dosing ranges, schedules and toxicities are included. Excerpt(s): The invention relates generally to use of inhibitors of 3-hydroxy-3methylglutaryl coenzyme A reductase in treating cancer. More specifically the invention relates to use of lovastatin and its homologues or analogues to treat human adenocarcinoma and selected sarcomas. Metastatic prostate cancer and stomach cancer are refractory to all available cytotoxic agents. There is no curative medical therapy for these common adult carcinomas. Lovastatin, widely used for treatment of hypercholesterolemia, is generally believed to be useful for synchronizing tumor cell growth in one cell cycle phase. Although there exist scattered reports of the cytotoxic activity of lovastatin, it has not been pursued as an anticancer drug. Adenocarcinoma is a group in the histological classification of cancer. For instance, 95% of prostate carcinomas are adenocarcinomas. Cancers of the stomach, intestine and colon are almost always adenocarcinomas, as are gall bladder cancers. Breast cancer is also an adenocarcinoma in perhaps 90% of the cases. Cancer of the esophagus is adenocarcinoma in about 10%-15% of cases and adenocarcinoma of the lung represents about 30% of pulmonary cancers. Web site: http://www.delphion.com/details?pn=US06040334__
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Patent Applications on Lovastatin 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 lovastatin: •
Genetic test to determine non-responsiveness to statin drug treatment Inventor(s): Rotter, Jerome I.; (Los Angeles, CA), Scheuner, Maren T.; (Manhattan Beach, CA), Taylor, Kent D.; (Santa Paula, CA), Yang, Huiying; (Cerritos, CA) Correspondence: Sidley Austin Brown & Wood; 555 West Fifth Street; Los Angeles; CA; 90013-1010; US Patent Application Number: 20020106657 Date filed: July 3, 2001 Abstract: In a method for detecting a genetic predisposition in a human for nonresponsiveness to statin drug treatment for coronary artery disease, nucleic acids comprising nucleotide sequences of the human lipoprotein lipase (LPL) gene are amplified and analyzed. Homozygosity for a variant allele in a non-coding or untranslated region of the 3' end of LPL, for example, LPL HindIII 2/2 or (TTTA).sub.n 4/4 genotypes, is linked to non-responsiveness to treatment with statin drugs, including lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, or cerivastatin. Oligonucleotide primer sequences, primer sets, and genetic testing kits allow the practitioner to practice the method and thus better individualize the treatment and improve the care of patients with coronary artery disease. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. This invention relates to the medical arts. In particular, it relates to the field of genetic testing methods and diagnostic kits. Statin drugs--the most potent lipid-lowering agents currently available--are 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. They include lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and cerivastatin. All these statin drugs share a common mechanism of action and have similar toxicity profiles. (E. von Kreutz and G. Schluter, Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase inhibitor, Am. J. Cardiol. 82(4B):11J-17J [1998];A. G. Ollson [1998]). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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HMG-COA reductase inhibitor extended release formulation Inventor(s): Chen, Chih-Ming; (Davie, FL), Chou, Joseph; (Coral Springs, FL), Wong, David; (Hollywood, FL) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20040029962 Date filed: June 25, 2003
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This has been a common practice outside the United States prior to December 2000.
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Abstract: Controlled release oral solid dosage form for the reduction of serum cholesterol levels in humans include a drug comprising an alkyl ester of hydroxy substituted naphthalenes (e.g., lovastatin) and a controlled release carrier, such that the dosage form provides a mean time to maximum plasma concentration (T.sub.max) of the drug which occurs at about 10 to about 32 hours after oral administration on a oncea-day basis to human patients. The dosage form provides a therapeutically effective reduction in serum cholesterol levels. Methods of reducing serum cholesterol levels in humans are also disclosed. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/339,494, filed Jun. 24, 1999, which is a continuation of U.S. Pat. No. 5,916,595, filed Dec. 12, 1997. The use of HMG-COA reductase inhibitors for the reduction of serum cholesterol levels is well known. These compounds include alkyl esters of hydroxy substituted naphthalenes which are orally effective in the reduction of serum cholesterol levels. Examples of these compounds include mevastatin which is described in U.S. Pat. No. 3,671,523; lovastatin which is described in U.S. Pat. No. 4,231,938; pravastatin which is described in U.S. Pat. No. 4,346,227; and simvastatin which is described in U.S. Pat. No. 4,444,784. All of these patents are incorporated by reference. Lovastatin is a metabolite which is produced by the natural fermentation of an fungus of the Aspergillus genus. Lovastatin acts systemically to lower blood serum cholesterol levels by disrupting the biosynthesis of cholesterol in the liver, where 70% to 80% of body cholesterol is produced. Specifically lovastatin interrupts a step in the endogenous production of cholesterol by inhibiting the HMG coenzyme A reductase from combining with bile acids in the digestive tract such that the bile acids are excreted from the body without reabsorption. With synthesis in the liver thusly inhibited, the liver cells must take cholesterol from the bloodstream, and they do so by increasing their production of cell surface receptors for LDL cholesterol. Lovastatin formulations are generally capable of lowering the blood serum cholesterol level by about 30-40%. The other compounds of this class are derived from natural or synthetic sources using well known procedures and have similar mechanisms of activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Inhibitors of nitric oxide synthase Inventor(s): Singh, Inderjit; (Mount Pleasant, SC) Correspondence: Michael R. Krawzsenek; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030195256 Date filed: October 18, 2002 Abstract: The current invention discloses novel methods for the inhibition of inducible nitric oxide synthesis (iNOS) and the production of NO. Methods of inhibiting the induction of proinflammatory cytokines are also described. Methods of treating various disease states, such as X-linked adrenoleukodystrophy, multiple sclerosis, Alzheimer's and septic shock using inhibitors of iNOS and cytokine induction are disclosed. The inhibitors include the exemplary compounds lovastatin, a sodium salt of phenylacetic acid (NaPA), FPT inhibitor II, N-acetyl cysteine (NAC), and cAMP. Excerpt(s): The present invention relates generally to the treatment of conditions involving undesired or pathological levels of inducible nitric oxide synthase (iNOS), e.g. septic shock or neuroinflammatory diseases. In one important aspect, the invention
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relates to methods of suppressing, inhibiting or preventing the accumulation of nitricoxide induced cytotoxicity by using inhibitors that block or suppress the induction of cytokines and/or inducible nitric oxide synthase. Another aspect of the invention is the treatment of conditions involving undesired or pathological levels of proinflammatory cytokines (i.e. TNF-.alpha., IL-1.beta., IL-2, IL-6, IL-8 and/or IFN-.gamma.) and/or iNOS. One important aspect of the invention relates to methods of suppressing, inhibiting, or preventing proinflammatory cytokines and/or iNOS induced or aggravated disorders including conditions involving the detrimental effects of inflammation (e.g. disorders such as lupus, rheumatoid arthritis, osteoarthritis, amyotrophic lateral sclerosis, and autoimmune disorders; ischemia/reperfusion; neuroinflammatory conditions such as Alzheimer's, stroke, multiple sclerosis, X-linked adrenoleukodystrophy; and the effects of aging). Nitric oxide (NO) is a potent pleiotropic mediator of physiological processes such as smooth muscle relaxation, neuronal signaling, inhibition of platelet aggregation and regulation of cell mediated toxicity. It is a diffusible free radical which plays many roles as an effector molecule in diverse biological systems including neuronal messenger, vasodilation and antimicrobial and antitumor activities (Nathan, 1992; Jaffrey et al., 1995). NO appears to have both neurotoxic and neuroprotective effects and may have a role in the pathogenesis of stroke and other neurodegenerative diseases and in demyelinating conditions (e.g., multiple sclerosis, experimental allergic encephalopathy, Xadrenoleukodystrophy) and in ischemia and traumatic injuries associated with infiltrating macrophages and the production of proinflamatory cytokines (Mitrovic et al., 1994; Bo et al, 1994; Merrill et al., 1993; Dawson et al., 1991, Kopranski et al., 1993; Bonfoco et al., 1995). A number of pro-inflammatory cytokines and endotoxin (bacterial lipopolysaccharide, LPS) also induce the expression of iNOS in a number of cells, including macrophages, vascular smooth muscle cells, epithelial cells, fibroblasts, glial cells, cardiac myocytes as well as vascular and non-vascular smooth muscle cells. Although monocytes/macrophages are the primary source of iNOS in inflammation, LPS and other cytokines induce a similar response in astrocytes and microglia (Hu et al, 1995; Galea et al, 1992). During inflammation, reactive oxygen species (ROS) are generated by various cells including activated phagocytic leukocytes; for example, during the neutrophil "respiratory burst", superoxide anion is generated by the membrane-bound NADPH oxidase. ROS are also believed to accumulate when tissues are subjected to inflammatory conditions including ischemia followed by reperfusion. Superoxide is also produced under physiological conditions and is kept in check by superoxide dismutates. Excessively produced superoxide overwhelms the antioxidant capacity of the cell and reacts with NO to form peroxynitrite, ONOO.sup.-, which may decay and give rise to hydroxyl radicals,.OH (Marietta, M., 1989; Moncada et al., 1989; Saran et al., 1990; Beckman et al. 1990). NO, peroxynitrite and.OH are potentially toxic molecules to cells including neurons and oligodendrocytes that may mediate toxicity through modification of biomolecules including the formation of iron-NO complexes of iron containing enzyme systems (Drapier et al, 1988), oxidation of protein sulfhydryl groups (Radi et al, 1991), nitration of proteins and nitrosylation of nucleic acids and DNA strand breaks (Wink et al., 1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Interferon-statin combination therapy Inventor(s): Cantrell, Stephen B.; (Brentwood, TN) Correspondence: Stephen B. Cantrell, Dds, MD; 111 Mckays Court; Brentwood; TN; 37027; US Patent Application Number: 20030232033 Date filed: February 20, 2003 Abstract: A method for pharmacological treatment of cancer and other diseases is presented which includes the novel combination of a statin (Hmg-CoA reductase inhibitor, such as lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, pravastatin, or newer agents), with an interferon (such as interferon alfa-2b or others) or an angiogenesis inhibitor (a very similar and often overlapping group of drugs which inhibit blood vessel growth and maintenance, such as thalidomide, angiostatin, endostatin, or other agents), and also including concurrent administration of selenium and calcium. The method disclosed in this invention is useful because it can prove more effective than previously known therapies for certain diseases and because its use may be more tolerable, less disfiguring, and less expensive than other methods. The method here disclosed can be readily reproduced by any person skilled in the art of treating disease. Excerpt(s): This application claims the benefit of U.S. provisional patent application No. 60/359265 mailed Feb. 20, 2002 and received for filing Feb. 21, 2002. Not applicable. Not applicable. No drawings are pertinent to understanding, making, and using the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Mammalian sterol synthesis as a target for chemotherapy against bacteria Inventor(s): Catron, Drew; (Chicago, IL), Haldar, Kasturi; (Chicago, IL), Lange, Yvonne; (Chicago, IL) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20030087430 Date filed: October 9, 2002 Abstract: The present invention discloses methods for treating, ameliorating, or preventing having an infection due to an intracellular vacuolar bacterium. The invention further exemplifies the use of mevinolin (lovastatin) in the treatment of intracellular vacuolar bacterial infections. Excerpt(s): The present invention relates to the treatment of bacterial infections due to intracellular bacteria, and to treating patients having a bacterial infection by inhibiting host cell sterol biosynthesis. Bacterial infections remain among the most common and deadly causes of human disease. Infectious diseases are the third leading cause of death in the United States and the leading cause of death worldwide (Binder et al. (1999) Science 284:1311-1313). Although, there was initial optimism in the middle of the last century that diseases caused by bacteria would be quickly eradicated, it has become evident that the so-called "miracle drugs" are not sufficient to accomplish this task. Antibiotic resistant pathogenic strains of bacteria have become commonplace, and bacterial resistance to the new variations of these drugs appears to be outpacing the ability of scientists to develop effective chemical analogs of the existing drugs (see, for
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example, Levy (March 1998) Scientific American, pp. 46-53). Therefore, new approaches to drug development are necessary to combat the ever-increasing number of antibioticresistant pathogens. Salmonella enterica is a significant cause of morbidity and mortality in the United States, responsible for 800,000 to 4 million cases each year. Serovar typhimurium accounts for over 25% of these cases (see, for example, National Antimicrobial Resistance Monitoring System, 1999 Annual Report). Whereas most Salmonella infections are self-limiting, acute intestinal inflammations, serious bacteremia can result in 3% to 10% of the infections. Dissemination most often occurs in young children, the elderly or those who are immunocompromised. In these cases, fluoroquinolones (i.e., ciprofloxacin) and cephalosporins (i.e., ceftriaxone) are commonly used for treatment. However, the rise of drug-resistant S. typhimurium strains is cause for great concern. More specifically, there is an increased incidence of a distinct multidrug-resistant form of typhimurim (DT104), which is resistant to five different antibiotics (ampicillin, chloramphenicol, streptomycin, sulfonamides and tetracyline) (Glynn et al. (1998) N. Engl. J. Med.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Medicinal compositions for the prevention or treatment of cardiac failure Inventor(s): Chu, Chia-Wei; (Kaoshung-city, TW), Hsiao, Chia-Ling; (Chung-ho city, TW), Lee, Bai-Ching; (Taipei, TW), Lee, Tsung Ming; (Taipei-city, TW), Su, Shen-Fang; (Tainan-city, TW) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20030181500 Date filed: February 26, 2003 Abstract: The present invention relates to pharmaceutical compositions, which contain a HMG-CoA reductase inhibitor selected from the group consisting of pravastatin, simvastatin, lovastatin, pitavastatin and ZD-4522 and an angiotensin II receptor antagonist and optionally further contain a calcium channel blocker. The compositions are for prevention or treatment of cardiac failure. Excerpt(s): This is a Continuation Application of PCT/JP10/07437 filed Aug. 29, 2001, which is incorporated herein by reference in its entirety. The present invention relates to pharmaceutical compositions for the prevention or treatment of cardiac failure, the prevention of ischemic coronary heart disease or the prevention of the recurrence of ischemic coronary heart disease, said pharmaceutical compositions containing a HMGCoA reductase inhibitor selected from the group consisting of pravastatin, simvastatin, lovastatin, pitavastatin and ZD-4522 and an angiotensin II receptor antagonist and optionally further containing a calcium channel blocker. The present invention also relates to methods for the prevention or treatment of cardiac failure, the prevention of ischemic coronary heart disease or the prevention of the recurrence of ischemic coronary heart disease, said methods comprising administering to a warm-blooded animal (particularly a human) in need of such treatment or prevention a pharmacologically effective amount of a pharmaceutical composition that contains a HMG-CoA reductase inhibitor selected from the group consisting of pravastatin, simvastatin, lovastatin, pitavastatin and ZD-4522 and an angiotensin II receptor antagonist and optionally further contains a calcium channel blocker. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of producing antihypercholesterolemic agents Inventor(s): Hutchinson, Charles R.; (Oakland, CA), Kennedy, Jonathan; (Hayward, CA), Park, Cheonseok; (Seoul, KR) Correspondence: Quarles & Brady Llp; 411 E. Wisconsin Avenue, Suite 2040; Milwaukee; WI; 53202-4497; US Patent Application Number: 20040033570 Date filed: March 28, 2002 Abstract: A method of increasing the production of lovastatin or monacolin J in a iovastatin-producing or non-lovastatin-producing organism is disclosed. In one embodiment, the method comprises the steps of transforming an organism with the A. terreus D4B segment, wherein the segment is translated and where an increase in lovastatin production occurs. Excerpt(s): Not applicable. Cholesterol and other lipids are transported in body fluids by low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Substances that effectuate mechanisms for lowering LDL-cholesterol may serve as effective antihypercholesterolemic agents because LDL levels are positively correlated with the risk of coronary artery disease. MEVACOR (lovastatin; mevinolin) and ZOCOR (simvastatin) are members of a group of active antihypercholesterolemic agents that function by inhibiting the rate-limiting step in cellular cholesterol biosynthesis, namely the conversion of hydroxymethylglutarylcoenzyme A (HMG-CoA) into mevalonate by HMG-CoA reductase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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METHODS AND COMPOSITIONS FOR ASSOCIATED WITH PULMONARY DISEASE
INHIBITING
INFLAMMATION
Inventor(s): HARLAN, JOHN M.; (SEATTLE, WA), LIU, LI; (REDMOND, WA), WINN, ROBERT K.; (BAINBRIDGE ISLAND, WA) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20010006656 Date filed: February 17, 1999 Abstract: The present invention provides an aerosol formulation of a 3-hydroxy-3methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor. The HMG-CoA reductase inhibitor can be, for example, a statin such as lovastatin, pravastatin, simvastatin, cerivastatin, fluvastatin, atorvastatin or mevastatin. The invention also provides a method of treating a pulmonary disease with an aerosol formulation of a HMG-CoA reductase inhibitor. Excerpt(s): The present invention relates generally to the fields of medicine and molecular pathology and, more specifically, to methods of treating an inflammatory lung disease. A variety of pulmonary diseases are associated with inflammation, including acute and chronic diseases. Pulmonary diseases associated with inflammation include, for example, asthma, interstitial pneumonitis, emphysema, chronic bronchitis, adult respiratory distress syndrome (ARDS) and cystic fibrosis. Many of the lung diseases associated with inflammation have a significant impact on human health, quality of life and productivity. For example, approximately 5% of the United States
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population has signs or symptoms of asthma. Chronic obstructive pulmonary disease, including chronic bronchitis and emphysema, is the fourth leading cause of death in the United States. In addition, the United States has approximately 100,000 cases of adult respiratory distress syndrome (ARDS), which can follow systemic or pulmonary insults. Cystic fibrosis is the most common lethal genetic disease in Caucasians, affecting approximately one in 2,000 births among Americans of European descent. Therefore, inflammatory lung diseases have a major impact on human health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical composition containing a combination of a statin and aspirin and method Inventor(s): Jain, Nemichand B.; (Cranbury, NJ), Ullah, Ismat; (Cranbury, NJ) Correspondence: Marla J. Mathias; Bristol-myers Squibb Company; Patent Department; P.O. Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020034546 Date filed: April 2, 2001 Abstract: A pharmaceutical composition is provided which is useful for cholesterol lowering and reducing the risk of a myocardial infarction, which includes a statin, such as pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin or fluvastatin, in combination with aspirin, in a manner to minimize interaction of aspirin with the statin and minimize side effects of aspirin. A method for lowering cholesterol and reducing risk of a myocardial infarction employing such composition is also provided. Excerpt(s): The present invention relates to a pharmaceutical composition which includes a statin cholesterol lowering agent and aspirin in a manner to minimize interaction of aspirin with the statin, for use in lowering cholesterol and reducing risk of a myocardial infarction, and to a method for lowering cholesterol and reducing risk of a myocardial infarction employing such composition. The use of aspirin for reducing the risk of a myocardial infarction and the use of statins for lowering cholesterol and preventing or treating atherosclerosis and cardiovascular disease and cerebrovascular disease are well documented. In fact, it is not uncommon that patients having elevated cholesterol levels who are at high risk for a myocardial infarction take both a statin and aspirin. However, use of both a statin and aspirin may require special care to insure that drug interaction, including physical and chemical incompatibility, and side effects, are kept to a minimum while achieving maximum benefit from these drugs. With regard to possible drug interaction, aspirin is an acid, while some of the statins, such as pravastatin, atorvastatin and cerivastatin, are alkali salts. Thus, mixing of such statins (alkali salts) with aspirin could result in aspirin hydrolysis as well as statin degradation. Pravastatin, on the other hand, is also a very acid labile compound. When pravastatin and aspirin are combined, the aspirin could cause pravastatin degradation which could result in lower bioavailability of pravastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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PROCESS FOR PRODUCING SIMVASTATIN Inventor(s): HORNE, STEPHEN E; (BURLINGTON, CA), MURTHY, K. S. KESHAVA; (BRANTFORD, CA), WEERATUNGA, GAMINI; (BRANTFORD, CA), YOUNG, SHAWN; (BRANTFORD, CA) Correspondence: Ivor M Hughes; Suite 200; 175 Commerce Valley Drive West; Thornhill; L3t7p6; CA Patent Application Number: 20010053859 Date filed: November 21, 1996 Abstract: A process for manufacturing Simvastatin is provided comprising reacting lovastatin with an organic boronic acid to produce a derivative of lovastatin with a hemiboronate group attached to the C-4 carbon of the pyranyl group, methylating the 2methylbutyryloxy group on the lovastatin derivative to form a 2,2-dimethylbutyryloxy group on the lovastatin derivative and thereafter removing the hemiboronate group to produce simvastatin. Excerpt(s): This invention relates to the preparation of SIMVASTATIN. This invention also relates to the purification of intermediates which may be used in the preparation of simvastatin. More broadly, this invention relates to processes for the alkylation at an.alpha.-carbon of an ester (containing one or two.alpha.-hydrogens) in a molecule which also contains a.beta.-hydroxylactone functional group with one or two.alpha.hydrogens. Mevastatin (also known as compactin) and lovastatin (also known as mevinolin) are naturally occuring HMG-CoA reductase inhibitors. These compounds have been used medicinally in the control of human serum cholesterol levels. Both compounds contain a (2S)-2-methylbutyryloxy substituent at the C-8 position of their hexahydronaphthalene nucleus and both produce medicinal analogues with increased potency towards HMG-CoA reductase when the aforementioned 2-methylbutyryloxy side chain is converted into a 2,2-dimethylbutyryloxy group. The analogue which is obtained from lovastatin by such a conversion is known as simvastatin. A method for the commercial scale production of simvastatin from lovastatin is the subject of the present invention. In the second procedure, the acetate of simvastatin is hydrolyzed using an enzymatic preparation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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PROCESS FOR PRODUCING, METHODS AND COMPOSITIONS OF CHOLESTEROL LOWERING AGENTS FROM HIGHER BASIDIOMYCETES MUSHROOMS Inventor(s): RESHETNIKOV, SERGEY V.; (KIEV, UA), WASSER, SOLOMON P.; (HAIFA, IL) Correspondence: Rashida A. Karmali, ESQ.; 230 Park Avenue; Suite 2525; New York; NY; 10169; US Patent Application Number: 20010016197 Date filed: October 15, 1999 Abstract: The present invention describes new and distinct strains of higher Basidiomycetes mushrooms, and a process for growing them in submerged culture. Specifically, the new strains of species of the genus Pleurotus offer superior yields of mushroom biomass and concentrations of biologically active compounds, for example,
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cholesterol-lowering compounds, lectins, proteins, essential amino acids, vitamins or polysaccharides. The process includes use of defined media and a simple one-step procedure of separating the lovastatin-containing nutriceuticals from culture broth. Excerpt(s): The present invention is directed to a process for culturing a variety of higher Basidiomycetes mushrooms to produce superior yields of biologically active nutriceuticals. The nutriceutical agents are isolated by a simple one-step process, and are formulated for use as dietary supplements to achieve normal human bodily functions in general, and to control particular abnormal factors, for example, hypercholesterolemia, in particular. Mushrooms or macrofungi with distinctive fruiting bodies of sufficient size to be seen with the naked eye, include about 10,000 species of varying degrees of edibility. Approximately 100 species have been tested for cultivation and only seven to eight have been cultivated on an industrial scale. The world production of cultivated edible mushrooms in 1994 was estimated to be about five million tons and was valued at about ten billion US dollars. The most popular species of cultivated edible mushrooms include Agaricus bisporus (J. Lge) Imbach, A. bitorquis (Qul.) Sacc., Lentinus edodes (Berk.) Sing, Pleurotus spp., Auricularia spp., Volvariella volvacea (Fr.) Sing., Flammulina velutipes (Fr.) Sing, Tremella fuciformis Berk., Hypsizygus marmoreus (Peck) Bigel., Pholita nameko (T. Ito) S. Ito et Imai, Grifola frondosa (Dicks.: Fr.) S. F. Gray, Hericium erinaceus (Bull.: Fr.) Pers., Dictyophora indusiata (Vent.: Pers.) Fischer, Stropharia rugosoannulata Farl. apud Murr., Lepista nuda (Bull.: Fr.) Cooke, Agrocybe aegerita (Brig.) Sing. The cultivation of fruiting bodies of mushrooms deals with living organisms, for example, the mushroom itself and other microorganisms which may either be harmful or beneficial. Therefore, the methods employed in mushroom cultivation require modifications depending upon the region being cultivated, substrates available, environmental conditions and species of microorganisms encountered. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for purifying lovastatin and simvastatin with reduced levels of dimeric impurities Inventor(s): Forgas, Ilona; (Debrecen, HU), Keri, Vilmos; (Debrecen, HU) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020002288 Date filed: February 27, 2001 Abstract: A process reducing the levels of dimeric impurities in a statin to less than 0.08% by treatment of a statin containing more than 0.08% dimeric impurities with a mild base in a suitable solvent mixture. Excerpt(s): This application claims the benefit of U.S. provisional application Serial No. 60/186868, filed Mar. 3, 2000, the content of which is incorporated herein by reference. The invention relates to a process of purifying Lovastatin or Simvastatin, which reduces the level of dimeric impurities in the resulting product. Lovastatin, is one member of a class of compounds, which are referred to generally as statins, are known to exist in open ring hydroxy acid and also in lactone form. The lactone form of Lovastatin is shown above. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for the isolation of lovastatin Inventor(s): Kumar, Parveen; (Haryana, IN), Narula, Pardeeo; (Delhi, IN), Rama, S.; (Haryana, IN) Correspondence: Jayadeep R. Deshmukh; Ranbaxy Pharmaceuticals INC.; 600 College Road East; Suite 2100; Princeton; NJ; 08540; US Patent Application Number: 20030215932 Date filed: April 24, 2003 Abstract: The process for the preparation and isolation of the hypolipaemic active substance lovastatin in substantially pure form having a purity of at least 95% which comprises lactonizing the mevinolinic acid to lovastatin in a totally aqueous medium. Excerpt(s): in a totally aqueous medium. It is known that certain mevalonate derivatives are active as anti-hyper-cholesterolemic agents, and these function by limiting cholesterol biosynthesis by inhibiting the enzyme HMG-CoA reductase. Lovastatin, Pravastatin, Simvastatin, Mevastatin, Atorvastatin and derivatives and analogs thereof are known as HMG-COA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus; others are obtained by treating the fermentation products using the method of chemical synthesis or they are the product of total chemical synthesis. Lovastatin is the first of the statins to be used widely and is manufactured by a fermentation-based process. It is produced as a secondary metabolite of the fungus Aspergillus terreus (U.S. Pat. No. 4,231,938) deposited in American Type Culture Collection under Nos. ATCC 20541 and ATCC 20542, and Monascus ruber deposited in Fermentation Research Institute Agency of Industrial Science and Technology, Ministry of International Trade and Industry, Japan (DE 3006216 Al) under No. Ferm. 4822. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for the preparation of sodium salts of statins Inventor(s): Kumar, M. Laltshmi; (Andhra Pradesh, IN), Kumar, Parveen; (Haryana, IN), Narula, Pardeep; (Delhi, IN), Raman, S.; (Tamil Nadu, IN) Correspondence: Jayadeep R Deshmukh; Ranbaxy Laboratories Limited; Suite 2100; 600 College Road East; Princeton; NJ; 08540; US Patent Application Number: 20030050502 Date filed: September 4, 2002 Abstract: A process for the preperation of sodium salts of statins, namely Compactin, Lovastatin and Pravastatin. Excerpt(s): The "statins" are a family of compounds that are usually inhibitors of 3hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. As HMG-CoA reductase inhibitors, the statins are able to reduce plasma cholesterol levels in various mammalian species, including humans and are therefore effective in the treatment of hypercholesterolaemia. Of all the statins known only two are produced directly by fermentation. These are Lovastatin (also called mevinolin or monacolin-K) and Compactin (also called mevastatin or ML-236B). Other statins are produced either chemically or enzymatically derived from Lovastatin
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or Compactin. One of these is Pravastatin, which has found favour recently as a more potent HMG-CoA reductase inhibitor than Lovastatin or Compactin and is disclosed in U.S. Pat. No. 4,346,227. Preparation of sodium salts of these compounds has been described in U.S. Pat. Nos. 4,448,979; 4,346,227; and 4,447,626. The methods employ use of alkali, acid, solvents, ion exchange chromatography followed by freeze drying operation using either the lactone or methyl ester form of Pravastatin as the raw material. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process of lactonization in the preparation of statins Inventor(s): Cho, Hong-Suk; (Icheon Si, KR), Choi, Kwang-Do; (Anyang Si, KR), Kim, Jin-Wan; (Seoul, KR), Lee, Kwang-Hyeg; (Seongnam Si, KR), Lee, Sang-Ho; (Anyang Si, KR), Yoon, Myeong-Sik; (Yongin Si, KR) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030050482 Date filed: July 23, 2002 Abstract: The present invention relates to a process for preparing lovastatin and simvastatin which comprises (1) performing step of a lactonization of mevinic acid and analog thereof compounds in the presence of a dehydrating agent and without an acid catalyst under nitrogen sweep; and then (2) making step of crystals at a high temperature. In the process of the present invention, lovastatin and simvastatin highly purified can be produced in a high yield and especially, heterodimers formed as a byproduct can be reduced in an amount remarkably. Therefore, the process of the present invention is convenient and economical. Excerpt(s): The present invention relates to a process for lactonizing mevinic acid or analog thereof. More particularly, the present invention relates to a process for preparing lovastatin and simvastatin in a high yield which comprises (1) performing a lactonization of mevinic acid and analog thereof compounds in the presence of a dehydrating agent without an acid catalyst under nitrogen sweep; and then (2) making crystals at a high temperature. Hypercholesterolemia is known as to be one of the prime risk factors for ischemic cardiovascular disease, such as arteriosclerosis. Bile acid sequestrants have been used to treat these diseases. They seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable. Statins are known to be active in a dihydroxylic acid form physiologically, but usually administered in a lactone form for patients. Therefore, it is necessary to develop an efficient method to perform a lactonization in a high yield. Since the lactonization is an equilibriated process, specific means should be utilized to transfer the equilibrium toward lactones as shown in Reaction Formular 1 in order to produce lactonized products in a high yield. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Processes for preparing calcium salt forms of statins Inventor(s): Lidor-Hadas, Rami; (Kafar-Saba, IL), Lifshitz-Liron, Revital; (Herzlia, IL), Niddam-Hildesheim, Valerie; (Even-Yeouda, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030114685 Date filed: August 16, 2002 Abstract: Processes for preparing a calcium salt of a statin from an ester derivative or protected ester derivative of the statin by using calcium hydroxide are provided. The ester or protected ester derivative is contacted with calcium hydroxide to obtain the calcium salt. Preferred statins are rosuvastatin, pitavastatin and atorvastatin, simvastatin and lovastatin. In processes beginning with a protected statin ester derivative, the protecting group is hydrolyzed during salt formation by contact with calcium hydroxide, or is contacted with an acid catalyst followed by contact with calcium hydroxide. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/312,812, filed Aug. 16, 2001 and U.S. patent application Ser. No. 10/037,412, filed Oct. 24, 2001, which claims the benefit of provisional application Serial No. 60/249,319, filed Nov. 16, 2000, all of which are incorporated herein by reference. The present invention relates to processes for preparing calcium salt forms of statins. The class of drugs called statins are currently the most therapeutically effective drugs available for reducing low-density lipoprotein (LDL) particle concentration in the blood stream of patients at risk for cardiovascular disease and thus, statins are used in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis. A high level of LDL in the bloodstream has been linked to the formation of coronary lesions that obstruct the flow of blood and can rupture and promote thrombosis. Goodman and Gilman, The Pharmacological Basis of Therapeutics, page 879 (9th Ed. 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Stabilized pharmaceutically effective composition and pharmaceutical formulation comprising the same Inventor(s): Kerc, Janez; (Ljubljana, SI), Pflaum, Zlatko; (Domzale, SI) Correspondence: Bromberg & Sunstein Llp; 125 Summer Street; Boston; MA; 02110-1618; US Patent Application Number: 20030109584 Date filed: November 15, 2002 Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis. The aforementioned active substances may be destabilized by the environmental factors, their degradation may also be accelerated by interactions with other pharmaceutical ingredients, such as fillers, binders, lubricants, glidants and disintegrating agents, therefore the pharmaceutical
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ingredients and the process for preparation of the pharmaceutical formulation should be meticulously chosen to avoid the aforementioned undesired interactions and reactions. The present invention relates to a HMG-CoA reductase inhibitor which is stabilized by forming a homogeneous composition with a buffering substance or a basifying substance. This homogeneous composition is suitably used as the active substance in a pharmaceutical formulation for the treatment of hypercholesterolemia and hyperlipidemia. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/591,322 filed on Jun. 9, 2000, which is currently pending. Its disclosure is incorporated herein by reference. The present invention relates to a newly stabilized HMG-CoA reductase inhibitor which is used in a pharmaceutical formulation being particularly suitable for the treatment of hypercholesterolemia and hyperlipidemia. More precisely, the present invention relates to a stabilized and very homogeneous composition mixture comprising a HMG-CoA reductase inhibitor, such as atorvastatin, pravastatin, fluvastatin and cerivastatin, or pharmaceutically active salts thereof, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance. The present invention relates more particularly to a stabilized and very homogeneous composition mixture comprising a HMG CoA reductase inhibitor or its pharmaceutically active salts, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance and which has increased stability as determined by a small change of its pH value and lactone content under storage and/or handling conditions. The present invention relates most particularly to a stabilized and very homogeneous composition mixture comprising pravastatin or its pharmaceutically active salts, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance and which has increased stability as determined by a small change of its pH value and lactone content under storage and/or handling conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Sublingual use of inhibitors in the biosynthesis of cholesterol Inventor(s): Weiss, Sol; (Reseda, CA) Correspondence: Mitchell, Silberberg & Knupp, Llp; Trident Center; 11377 West Olympic Boulevard; Los Angeles; CA; 90064; US Patent Application Number: 20030100493 Date filed: June 4, 2002 Abstract: The present invention is a method introducing the sublingual placement of statin drugs whose names include: Fluvastatin, Atorvastatin, Lovastatin, Pravastatin and Simvastatin for heart related and other vascular emergencies. Current research challenges are developing many new derivatives and new classes of these HMG-CoA reductase inhibitors, which alter the biosynthesis of cholesterol. This method applies these medications (statin drugs) in a form such as sublingual (under the tongue) for rapid absorption and immediate high blood levels similar to that of nitroglycerin. The advantage of this method is that it will benefit those who are stricken with strokes and heart attacks by therefore saving lives and costs of medical care. Excerpt(s): This application contains subject matter of my provisional application Serial No. 60/306,977, filed Jul. 19, 2001, entitled Sublingual Use of Inhibitors in the
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Biosynthesis of Cholesterol, and in my provisional application Serial No. 60/314,532, filed Aug. 23, 2001, entitled Amendments to Serial No. 60/306,977. There is disclosed a method and combination of components to administer statin drugs in a beneficial method and manner. This method includes the sublingual administration of drugs selected from the class of drugs known as statin drugs. In addition to the method, there is disclosed a method and attendant components for administering sublingual medication or medications for emergency stabilization of ruptured plaques; suppression of thrombus or aggregation of platelets; alteration of inflammatory responses; improvement of endothelial function; reduction in cell death and augmentation of vasodilation. Disclosed is the combination of medications, such as a statin drug and nitroglycerin, and others, in sublingual administration. In addition, it has been found that combinations of other statin class drugs with other cholesterol lowering drugs such as niacin and other complications rupture, thrombus and platelet aggregation, inflammation, compromised endothelial function, vasoconstriction and cell death. These statin medications both by their own merits and in combinations with other drugs will lend to more beneficial and/or synergistic effects. Statins are like the new aspirins for use in the field of emergency medicine. The new Heart Protection Study (HPS) done in England reflects this latest and major breakthrough study of the statin class of drugs showing a reduction of adverse major vascular events over 5.5 years of treatment in high-risk patients. Most everyone is aware of the beneficial role of aspirin in emergency medicine. Furthering this theory of use ill medical emergencies are new reports of statins reducing infarct size in stroke patients. Statins favor endothelial nitric oxide synthase (eNOS) and block inducible nitric oxide synthase (iNOS) effects. These effects are neuroprotective by preserving blood flow and limiting neurological insult. Another ongoing study shows that a neurotoxin, Beta-Amyloid, derived from the Amyloid Precursor Protein (APP), was found embedded in the membranes of cells as disclosed in Alzheimer's disease, multiple sclerosis, vascular inflammations and other degenerative changes. Similar changes are recognized in patients with coronary artery and vascular diseases therefore implicating the plaque deposits occur elsewhere in the body as a result of the high cholesterol contents in tissues. High cholesterol induces these toxic changes. 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 lovastatin, 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 “lovastatin” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on lovastatin. You can also use this procedure to view pending patent applications concerning lovastatin. 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 5. PERIODICALS AND NEWS ON LOVASTATIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lovastatin.
News Services and Press Releases One of the simplest ways of tracking press releases on lovastatin 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 “lovastatin” (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 lovastatin. 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 “lovastatin” (or synonyms). The following was recently listed in this archive for lovastatin: •
Lovastatin induces apoptosis in thyroid cancer cells, but clinical value uncertain Source: Reuters Industry Breifing Date: July 30, 2003
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Ezetimibe plus lovastatin safe and effective for primary hypercholesterolemia Source: Reuters Industry Breifing Date: March 13, 2003
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Generic makers to ship their versions of Merck's Mevacor Source: Reuters Industry Breifing Date: December 18, 2001
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Generic makers to ship their versions of Mevacor Source: Reuters Medical News Date: December 18, 2001
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Niacin/lovastatin compound a promising total lipid modifier Source: Reuters Industry Breifing Date: September 13, 2001
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Primary prevention with lovastatin effective for patients at moderate risk of CVD Source: Reuters Medical News Date: June 21, 2001
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Court grants 10 additional days of marketing exclusivity for Merck's Mevacor Source: Reuters Industry Breifing Date: June 21, 2001
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Mylan confirms delay of generic lovastatin approval Source: Reuters Industry Breifing Date: June 19, 2001
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Mylan announces FDA approval of Mevacor generic despite restraining order Source: Reuters Industry Breifing Date: June 18, 2001
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Court delays expiration of exclusivity for Merck's Mevacor Source: Reuters Industry Breifing Date: June 18, 2001
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Andrx's Lovastatin XL application accepted for filing by FDA Source: Reuters Industry Breifing Date: June 01, 2001
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Andrx files NDA for extended-release lovastatin Source: Reuters Industry Breifing Date: April 02, 2001
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OTC availability of lovastatin 10 mg appears feasible Source: Reuters Industry Breifing Date: March 09, 2001
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FDA tentatively approves Faulding's generic lovastatin Source: Reuters Industry Breifing Date: December 20, 2000
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FDA panel vetoes OTC version of Merck's Mevacor cholesterol drug Source: Reuters Industry Breifing Date: July 17, 2000
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Eon receives FDA approval for generic formulation of Mevacor Source: Reuters Industry Breifing Date: May 02, 2000
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Lovastatin potentiates sulindac-induced apoptosis in colon cancer cells Source: Reuters Medical News Date: October 01, 1999
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Lovastatin boosts ability of NSAIDs to ward off colorectal cancer Source: Reuters Medical News Date: April 13, 1999
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FDA expands indications for lovastatin use Source: Reuters Medical News Date: March 18, 1999
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Lovastatin reduces LDL cholesterol in adolescent males with heterozygous familial hypercholesterolemia Source: Reuters Medical News Date: January 13, 1999
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Caution urged for diltiazem/lovastatin coadministration Source: Reuters Medical News Date: October 30, 1998
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Lovastatin induces apoptosis in malignant mesothelioma cells Source: Reuters Medical News Date: May 22, 1998
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Grapefruit juice increases serum levels of lovastatin and its metabolite Source: Reuters Medical News Date: May 14, 1998
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Lovastatin Study Results Indicate Benefits In Healthy Subjects Source: Reuters Medical News Date: November 14, 1997
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Lovastatin Effective And Well Tolerated In Elderly Patients Source: Reuters Medical News Date: January 29, 1997
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Lovastatin Therapy Reduces Myocardial Ischemia Within 4 to 6 Months Source: Reuters Medical News Date: January 21, 1997
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Lovastatin Effective For Children With Severe Familial Hypercholesterolemia Source: Reuters Medical News Date: May 15, 1996
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Merck's Zocor And Mevacor Show Strong Growth Source: Reuters Medical News Date: April 18, 1996
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Lovastatin And Dietary Therapy: Reduces Carotid Arterial Wall Thickness Source: Reuters Medical News Date: March 20, 1996
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Escape Phenomenon During Lovastatin Therapy Overcome By Stopping Treatment Briefly Source: Reuters Medical News Date: July 24, 1995
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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
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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 “lovastatin” (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 “lovastatin” (or synonyms). If you know the name of a company that is relevant to lovastatin, 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 “lovastatin” (or synonyms).
Academic Periodicals covering Lovastatin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lovastatin. In addition to these sources, you can search for articles covering lovastatin 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.”
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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 6. 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 lovastatin. 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 lovastatin. 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 lovastatin: HMG-CoA Reductase Inhibitors •
Systemic - U.S. Brands: Baycol; Lescol; Lipitor; Mevacor; Pravachol; Zocor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202284.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. 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. 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 Institute11: •
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
•
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
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
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.12 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:13 •
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
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
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
•
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/
•
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
•
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
12
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). 13 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 NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lovastatin” (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 4639 3 800 15 17 5474
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “lovastatin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
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.
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Coffee Break: Tutorials for Biologists19 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 staff.20 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.21 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/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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. 21 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.
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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 lovastatin 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 lovastatin. 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 lovastatin. 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 “lovastatin”:
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Circulatory Disorders http://www.nlm.nih.gov/medlineplus/circulatorydisorders.html Gout and Pseudogout http://www.nlm.nih.gov/medlineplus/goutandpseudogout.html Leg Injuries and Disorders http://www.nlm.nih.gov/medlineplus/leginjuriesanddisorders.html Medicines http://www.nlm.nih.gov/medlineplus/medicines.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html 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 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 “lovastatin” (or synonyms). The following was recently posted: •
AACE medical guidelines for clinical practice for the diagnosis and treatment of dyslipidemia and prevention of atherogenesis Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2000 Mar-April; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2199&nbr=1425&a mp;string=lovastatin
•
Cardiac rehabilitation Source: Agency for Healthcare Research and Quality - Federal Government Agency [U.S.]; 1995 October (reviewed 2000); 202 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1049&nbr=93& ;string=lovastatin
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Cardiovascular disease in women: a guide to risk factor screening, prevention and management Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3487&nbr=2713&a mp;string=lovastatin
•
Diagnosis and management of hypertension in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 May; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2579&nbr=1805&a mp;string=lovastatin
•
Drug treatment for hyperlipidaemias Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 4 (revised 2003 October 5); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4357&nbr=3283&a mp;string=lovastatin
•
Glomerulonephritis Source: National Committee on Renal Care (Singapore); 2001 October; 132 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2971&nbr=2197&a mp;string=lovastatin
•
HIV disease management Source: University of Texas Medical Branch Correctional Managed Care - Academic Institution; 1996 September (revised 2002 Jul); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3477&nbr=2703&a mp;string=lovastatin
•
Hyperlipidemia Source: University of Texas Medical Branch Correctional Managed Care - Academic Institution; 1998 February (revised 2002 Jul); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3552&nbr=2778&a mp;string=lovastatin
•
Lipid management in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jul); 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3410&nbr=2636&a mp;string=lovastatin
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Lipids and the primary prevention of coronary heart disease. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 September; 60 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2909&nbr=2135&a mp;string=lovastatin
•
Screening and management of lipids Source: University of Michigan Health System - Academic Institution; 2000 May (revised 2003 Apr); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4114&nbr=3159&a mp;string=lovastatin
•
Secondary prevention of coronary heart disease following myocardial infarction. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 January; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2303&nbr=1529&a mp;string=lovastatin
•
Treatment of acute myocardial infarction Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 May (revised 2002 Nov); 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3659&nbr=2885&a mp;string=lovastatin
•
VHA/DoD clinical practice guideline for the management of dyslipidemia in primary care Source: Department of Defense - Federal Government Agency [U.S.]; 2001 December; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3187&nbr=2413&a mp;string=lovastatin 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 lovastatin. 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
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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/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lovastatin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lovastatin. 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 lovastatin. 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 “lovastatin” (or a synonym), and you will receive information on all relevant organizations listed in the database.
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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 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 “lovastatin”. 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 “lovastatin” (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 “lovastatin” (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.22
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
22
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)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
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
•
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
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
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/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
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/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 115
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
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/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
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
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
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
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
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/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
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/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
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
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
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/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 117
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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/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
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
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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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LOVASTATIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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 Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] 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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [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] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous 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] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different
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from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adrenoleukodystrophy: A chromosome X-linked disease. [NIH] 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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium 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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] 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] 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] 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
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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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [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] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [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] 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] 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] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia
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usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] 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] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [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] 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] Anomalies: Birth defects; abnormalities. [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] 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 the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] 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]
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Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [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] Aqueous: Having to do with water. [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] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] 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
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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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [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] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] 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] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Azoxymethane: A potent carcinogen and neurotoxic compound. It is particularly effective in inducing colon carcinomas. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [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
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bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [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] 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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bezafibrate: Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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
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modifier (BRM) therapy. [NIH] Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived 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] Bladder: The organ that stores urine. [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] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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 Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [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 Regeneration: Renewal or repair of lost bone tissue. It excludes bony callus formed after bone fracture but not yet replaced by hard bone. [NIH] Bony Callus: The bony deposit formed between and around the broken ends of a fractured bone during normal healing. [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] 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
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walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [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] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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] 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 Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [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] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carboxy: Cannabinoid. [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]
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Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopathy: Any disorder or disease of the heart. In addition to heart disease of inflammatory origin, there are arteriosclerotic cardiopathy, due to arteriosclerosis; fatty cardiopathy, due to growth of fatty tissue; hypertensive cardiopathy, due to high blood pressure; nephropathic cardiopathy, due to kidney disease, thyrotoxic cardiopathy, due to thyroid intoxication; toxic cardiopathy, due to the effect of some toxin; and valvular cardiopathy, due to faulty valve action. [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] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [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] 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] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [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 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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain
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functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [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] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] 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] 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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [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] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti).
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This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Choleretic: A choleretic agent. [EU] Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [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] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [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] 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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [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] 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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Claudication: Limping or lameness. [EU] 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] 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
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medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] 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] 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] Coal Tar: A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed). [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [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] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH]
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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 Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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 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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU]
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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] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] 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] Coronary Vessels: The veins and arteries of the heart. [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] 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] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [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]
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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] 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, 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] 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] 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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] 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] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [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] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive
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stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] 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] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] 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] 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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [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] 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] 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
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(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] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [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 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] Diurnal: Occurring during the day. [EU] Dolichol: Eicosamethyl octacontanonadecasen-1-o1. Polyprenol found in animal tissues that contains about 20 isoprene residues, the one carrying the alcohol group being saturated. [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-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [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] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH]
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Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Emboli: 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] 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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [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] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH]
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Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [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 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] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [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]
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Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [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]
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] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] 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] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] 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] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [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]
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Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [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, 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] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products. [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] 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
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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] Gallate: Antioxidant present in tea. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gastric: Having to do with the stomach. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [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]
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 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [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
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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] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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] 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]
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] 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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Gonadal: Pertaining to a gonad. [EU] 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] 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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH]
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Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [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] 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] 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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] 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]
Hepatic: Refers to the liver. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH]
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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: 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]
High-density lipoproteins: Lipoproteins that contain a small amount of cholesterol and carry cholesterol away from body cells and tissues to the liver for excretion from the body. Low-level HDL increases the risk of heart disease, so the higher the HDL level, the better. The HDL component normally contains 20 to 30 percent of total cholesterol, and HDL levels are inversely correlated with coronary heart disease risk. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [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] Hormonal: Pertaining to or of the nature of a hormone. [EU] 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] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] 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 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] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [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] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain
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collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperlipidemia: An excess of lipids in the blood. [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] 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] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [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] Hypnotic: A drug that acts to induce sleep. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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 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 factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]
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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, wires, or catheters is placed directly into or near the tumor. Also called [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] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] 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 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]
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] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inorganic: Pertaining to substances not of organic origin. [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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix
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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] 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 Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [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-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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intermittent Claudication: A symptom complex characterized by leg pain and weakness brought on by walking, with the disappearance of the symptoms following a brief rest. [NIH] 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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]
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,
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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] 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] Iridium: A metallic element with the atomic symbol Ir, atomic number 77, and atomic weight 192.22. [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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isoprenoid: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH]
Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [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]
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Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] 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] 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] 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] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [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]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] 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] Library Services: Services offered to the library user. They include reference and circulation. [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] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] 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 cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol,
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and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [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]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [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] Lubricants: Oily or slippery substances. [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] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]
Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] 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]
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Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [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] Manic: Affected with mania. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [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]
Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [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] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Membrane: A very thin layer of tissue that covers a surface. [NIH] 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
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leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] 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] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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 body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [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] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU]
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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] 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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] 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] Myelin: The fatty substance that covers and protects nerves. [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] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart 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. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic
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heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics. [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] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] 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] 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] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] 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] 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] 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] Neuroectodermal tumor: A tumor of the central or peripheral nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [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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Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [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] 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] 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]
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] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [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
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environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [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] 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] 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] 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] 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] 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]
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] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [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] Pathogen: Any disease-producing microorganism. [EU]
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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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] 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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [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 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] Perivascular: Situated around a vessel. [EU] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] 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] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH]
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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] 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] 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] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] 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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous
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membrane). [NIH] 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] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: 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] 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] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] 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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] 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] 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] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [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] 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]
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Prophylaxis: An attempt to prevent disease. [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 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] 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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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 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] 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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They
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function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [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] Psychosine: An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside. [NIH] 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] 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 Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [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] 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
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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] Radioactive: Giving off radiation. [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] 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 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] 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] 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] 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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [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] 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] 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
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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] 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] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [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] 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] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue 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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [NIH]
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Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [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] 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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] 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] 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] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] 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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as
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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] 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] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [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] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Welfare: Organized institutions which provide services to ameliorate conditions of need or social pathology in the 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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH]
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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] 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] 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] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] 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] Steady state: Dynamic equilibrium. [EU] 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] 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]
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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] Stool: The waste matter discharged in a bowel movement; feces. [NIH] 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 inhibiting the initiation and elongation processes during protein synthesis. [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] 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] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [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] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] 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] 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] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [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] 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
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response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [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] 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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] 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] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH]
Dictionary 171
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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] 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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [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] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] 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] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] 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] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] 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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [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]
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Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [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] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat 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] 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] 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] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
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] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [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] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] 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]
Dictionary 173
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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] 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] Vasodilators: Any nerve or agent which induces dilatation of the 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] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [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 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] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] 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] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization.
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It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] 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]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] 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] Xanthoma: A tumour composed of lipid-laden foam cells, which are histiocytes containing cytoplasmic lipid material. Called also xanthelasma. [EU] Xenograft: The cells of one species transplanted to another species. [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]
175
INDEX A Abdominal, 58, 121, 158 Abdominal Pain, 58, 121 Aberrant, 61, 121 Acceptor, 121, 151, 158, 171 Acetylcholine, 121, 157 Acetylcysteine, 11, 16, 121 Acidity, 65, 121 Acne, 121, 150 Acne Vulgaris, 121, 150 Acremonium, 121, 131 Actin, 61, 121 Acute myelogenous leukemia, 121 Acute myeloid leukemia, 22, 30, 35, 121 Acute nonlymphocytic leukemia, 121 Acute renal, 27, 121 Acyl, 62, 63, 70, 121 Acylation, 71, 121 Adaptability, 121, 130, 131 Adenocarcinoma, 38, 40, 60, 75, 122, 157 Adipose Tissue, 122, 152 Adrenoleukodystrophy, 33, 34, 37, 66, 67, 77, 78, 122 Adverse Effect, 12, 58, 122, 150, 167 Aerobic, 72, 122, 172 Aerosol, 81, 122 Affinity, 45, 122, 126, 167 Agar, 122, 160 Age of Onset, 122, 172 Algorithms, 122, 128 Alkaline, 122, 123, 129, 159 Alkylation, 83, 122 Allergen, 122, 166 Allergic Rhinitis, 122, 129 Allograft, 27, 122 Allylamine, 122, 123 Alopecia, 122, 136 Alpha Particles, 122, 163 Alternative medicine, 94, 122 Ameliorating, 79, 123 Amine, 69, 70, 123 Amino Acid Sequence, 123, 124, 143 Amlodipine, 21, 123 Ammonia, 123 Ampicillin, 80, 123 Amyloid, 18, 40, 45, 89, 123, 144 Anaesthesia, 123, 148 Anal, 123, 140, 142
Analgesic, 123, 169 Analog, 86, 123 Anaplastic, 20, 35, 37, 123 Anatomical, 123, 131, 134, 137, 148, 154, 166 Aneurysm, 123, 173 Angina, 24, 123, 157 Angina Pectoris, 24, 123 Angiogenesis, 79, 124, 140 Angiogenesis inhibitor, 79, 124, 140 Angioplasty, 21, 124, 155 Angiotensin-Converting Enzyme Inhibitors, 20, 124 Animal model, 8, 10, 11, 16, 124 Anomalies, 124, 170 Antagonism, 124, 138 Antibiotic, 60, 79, 123, 124, 129, 130, 136, 138, 141, 159, 168, 169 Antibodies, 10, 124, 145, 146, 152, 160 Antibody, 5, 122, 124, 134, 145, 146, 147, 148, 150, 153, 155, 164, 166, 168, 174 Anticoagulant, 124, 162, 173 Antifungal, 124, 150 Antigen, 122, 124, 125, 134, 137, 146, 147, 148, 149, 153, 154, 166 Antigen-presenting cell, 125, 137 Anti-inflammatory, 5, 13, 125, 126, 130, 137, 144, 169 Anti-Inflammatory Agents, 125, 126, 130 Antimicrobial, 67, 78, 80, 125, 132 Antineoplastic, 125, 136, 138, 149, 158 Antioxidant, 10, 24, 67, 78, 125, 126, 143, 158 Antiproliferative, 19, 125 Antipruritic, 125, 132, 133 Antiviral, 18, 121, 125, 149 Anus, 123, 125, 128, 133 Apolipoproteins, 125, 143, 152 Apoptosis, 11, 13, 14, 16, 20, 22, 25, 29, 30, 31, 33, 35, 36, 37, 38, 39, 91, 92, 93, 125, 130 Aqueous, 85, 125, 127, 136, 139, 146, 151 Arachidonic Acid, 125, 162 Arcus Senilis, 125, 131 Arginine, 125, 149, 157 Arterial, 12, 53, 93, 122, 125, 132, 147, 157, 162, 170
176
Lovastatin
Arteries, 54, 65, 72, 125, 128, 135, 150, 152, 154, 155 Arterioles, 125, 126, 128, 129, 155 Arteriolosclerosis, 125, 126 Arteriosclerosis, 25, 28, 34, 48, 64, 70, 72, 73, 86, 125, 130, 147 Artery, 4, 28, 31, 48, 58, 73, 75, 76, 81, 89, 123, 124, 125, 126, 135, 139, 150, 155, 165 Articular, 126, 158 Asbestos, 126, 153, 154 Ascorbic Acid, 30, 126, 147 Aspergillosis, 126, 150 Aspirin, 5, 82, 89, 126 Assay, 8, 24, 126, 172 Astrocytes, 10, 67, 78, 126, 153, 154 Astrocytoma, 20, 126, 143, 144 Atrial, 126, 173 Atrial Fibrillation, 126, 173 Atrophy, 126, 156 Autoimmune disease, 8, 10, 126, 155 Azoxymethane, 13, 126 B Bacteremia, 80, 126 Bacteria, 15, 79, 121, 124, 126, 127, 139, 140, 141, 144, 152, 154, 164, 168, 171, 172, 173 Bacterial Infections, 79, 127, 131, 144, 165 Bacteriophage, 127, 160, 171 Bacteriostatic, 127, 141 Bacterium, 79, 127 Barbiturate, 127, 170 Basal Ganglia, 127, 144 Base, 65, 69, 71, 84, 127, 136, 137, 142, 143, 150, 159, 170, 172 Basophils, 127, 144, 151 Benign, 125, 127, 145, 154, 164 Beta-pleated, 123, 127 Bezafibrate, 22, 40, 48, 127 Bile, 4, 54, 64, 70, 77, 86, 127, 131, 132, 140, 143, 152, 168, 170 Bile Acids, 54, 77, 127, 168, 170 Bile Acids and Salts, 127 Biliary, 127, 132 Bioavailability, 8, 82, 127 Biochemical, 6, 7, 15, 26, 37, 38, 39, 42, 44, 75, 127, 151, 158 Biological response modifier, 127, 128, 149 Biological therapy, 127, 145 Biomass, 64, 83, 128 Biotechnology, 18, 19, 94, 103, 128 Bladder, 75, 128, 134, 155, 162, 172 Blastomycosis, 128, 150
Blood Coagulation, 128, 129 Blood pressure, 12, 20, 54, 128, 130, 147, 167 Blood vessel, 79, 124, 128, 129, 130, 131, 132, 139, 140, 144, 150, 167, 169, 170, 173 Blood Volume, 9, 128 Body Fluids, 81, 128, 129, 167 Bone Marrow, 15, 121, 128, 136, 147, 152, 168 Bone Regeneration, 15, 128 Bony Callus, 128 Bowel, 5, 123, 128, 137, 149, 151, 169 Bowel Movement, 128, 137, 169 Brachytherapy, 128, 149, 150, 164, 174 Bradykinin, 128, 157 Branch, 61, 109, 117, 129, 136, 139, 159, 163, 168, 170 Breakdown, 129, 137, 143, 167 Broad-spectrum, 123, 129, 130, 131 Bronchi, 129, 171 Bronchitis, 81, 129 Buccal, 129, 152 Budesonide, 8, 129 Bypass, 48, 129, 155 C Cachexia, 5, 129 Calcification, 125, 129 Calcium, 21, 79, 80, 87, 123, 126, 129, 134, 138, 156, 167 Calcium channel blocker, 80, 123, 129 Calcium Hydroxide, 87, 129 Capillary, 128, 129, 152, 173 Carbohydrates, 129, 130 Carboxy, 63, 129 Carcinogen, 8, 126, 129 Carcinogenesis, 5, 13, 38, 129, 131 Carcinogenic, 129, 133, 148, 158, 168 Carcinoma, 37, 60, 129, 157 Cardiac, 58, 67, 72, 74, 78, 80, 108, 122, 126, 130, 135, 155, 156, 165, 168 Cardiomyopathy, 48, 58, 130 Cardiopathy, 65, 72, 130 Cardiovascular, 4, 12, 20, 26, 64, 66, 70, 82, 86, 87, 109, 130 Cardiovascular disease, 4, 64, 66, 70, 82, 86, 87, 109, 130 Carnitine, 66, 130 Caspase, 13, 31, 130 Catheterization, 124, 130, 155 Causal, 130, 140 Cause of Death, 16, 58, 75, 79, 82, 130 Ceftriaxone, 80, 130
Index 177
Celecoxib, 7, 13, 130 Cell, 6, 7, 8, 10, 12, 13, 14, 16, 17, 19, 22, 26, 31, 34, 35, 36, 37, 38, 39, 43, 48, 59, 60, 61, 64, 66, 67, 75, 77, 78, 79, 89, 121, 125, 126, 127, 128, 130, 132, 134, 135, 136, 137, 140, 141, 142, 143, 145, 146, 147, 148, 149, 150, 151, 154, 155, 156, 157, 160, 162, 163, 164, 167, 171, 172, 173, 174 Cell Adhesion, 36, 130, 149 Cell Death, 38, 43, 89, 125, 130 Cell Differentiation, 130, 167 Cell Division, 126, 130, 136, 145, 155, 160 Cell membrane, 64, 130, 137, 150, 160 Cell proliferation, 13, 36, 38, 126, 130, 167 Cell Survival, 130, 145 Cellulose, 129, 131, 143, 160 Central Nervous System, 12, 121, 131, 132, 143, 144, 145, 154, 155 Central Nervous System Infections, 131, 145 Cephalosporins, 80, 131 Cerebral, 9, 16, 127, 131, 144 Cerebral hemispheres, 127, 131, 144 Cerebrotendinous Xanthomatosis, 54, 131 Cerebrovascular, 82, 130, 131 Cerebrum, 131 Cervix, 131, 165 Character, 124, 131, 136 Chemoprevention, 5, 7, 8, 14, 131 Chemopreventive, 5, 7, 8, 13, 131 Chemotaxis, 11, 131 Chemotherapeutic agent, 33, 131 Chemotherapy, 79, 131 Chenodeoxycholic Acid, 54, 131 Chin, 131, 154 Chlorophyll, 132, 142 Cholecystokinin, 48, 132 Choleretic, 131, 132 Cholestanol, 54, 132 Cholesterol Esters, 132, 151 Cholestyramine, 28, 74, 132 Chondrocytes, 132, 141 Chromatin, 8, 125, 132, 140 Chromosomal, 132 Chromosome, 122, 132, 172 Chronic, 81, 121, 128, 129, 132, 148, 150, 151, 169 Chronic Disease, 81, 129, 132, 151 Chylomicrons, 132, 152 Ciprofloxacin, 80, 132 CIS, 63, 132 Citrus, 126, 132
Claudication, 53, 132 Clear cell carcinoma, 132, 137 Clinical Medicine, 41, 132, 161 Clinical study, 132, 135 Clinical trial, 4, 8, 10, 13, 14, 16, 53, 55, 58, 103, 133, 135, 136, 138, 162, 164 Cloning, 60, 128, 133 Coagulation, 128, 133, 145, 171, 173 Coal, 133, 156 Coal Tar, 133, 156 Cod Liver Oil, 133, 139 Coenzyme, 4, 18, 19, 29, 37, 42, 58, 59, 61, 68, 74, 75, 76, 77, 81, 85, 126, 133, 152, 163, 167 Cofactor, 133, 162 Cognition, 12, 133 Cohort Studies, 133, 140 Colestipol, 3, 43, 48, 133 Collagen, 33, 123, 133, 142, 160, 161 Colon, 5, 13, 33, 38, 75, 92, 126, 133, 134, 151 Colorectal, 13, 43, 62, 93, 134 Colorectal Cancer, 43, 93, 134 Combination Therapy, 39, 42, 79, 134 Complement, 134, 143, 149, 166 Complete remission, 134, 164 Compliance, 12, 134 Computational Biology, 103, 134 Conjugated, 63, 127, 131, 134, 136, 144 Connective Tissue, 126, 128, 133, 134, 142, 143, 165 Constriction, 134, 150, 173 Constriction, Pathologic, 134, 173 Consumption, 12, 16, 134 Contractility, 124, 134 Contraindications, ii, 135 Control group, 54, 135 Controlled clinical trial, 14, 135 Coordination, 135, 155 Cornea, 131, 135 Coronary Arteriosclerosis, 74, 135, 155 Coronary Circulation, 124, 135, 157 Coronary Disease, 45, 135 Coronary heart disease, 5, 12, 24, 45, 65, 66, 80, 110, 130, 135, 146 Coronary Thrombosis, 135, 154, 155 Coronary Vessels, 135 Cortisone, 135, 137 Cranial, 135, 145, 159 Craniocerebral Trauma, 135, 145 Cross-Sectional Studies, 135, 140 Curative, 75, 135, 157, 170
178
Lovastatin
Cutaneous, 7, 14, 128, 135, 152 Cyclic, 135, 145, 157, 162 Cyclin, 6, 19, 26, 135 Cyclophosphamide, 10, 136 Cyclosporine, 32, 44, 136 Cytochrome, 24, 37, 136, 165 Cytochrome b, 136, 165 Cytogenetics, 5, 136 Cytokine, 12, 66, 77, 136, 170 Cytoplasm, 125, 127, 130, 136, 140, 144 Cytosine, 32, 44, 136, 163 Cytoskeleton, 61, 136, 149, 154 Cytotoxic, 75, 136, 164, 167 Cytotoxicity, 15, 44, 61, 67, 78, 122, 136 D Daunorubicin, 136, 138 De novo, 35, 136 Defense Mechanisms, 136, 149 Degenerative, 89, 136, 158 Deletion, 125, 136 Dendrites, 136, 137, 156 Dendritic, 10, 137, 153 Dendritic cell, 10, 137 Density, 27, 38, 42, 45, 127, 137, 138, 152, 158 Depolarization, 137, 167 Depressive Disorder, 137, 152 Dermatologist, 14, 137 Dermatology, 14, 137 DES, 63, 137 Deuterium, 137, 146 Dexamethasone, 8, 137 Diabetes Mellitus, 23, 137, 144, 145 Diagnostic procedure, 57, 94, 137 Diarrhea, 58, 132, 137 Diastolic, 137, 147 Dietary Fats, 3, 137 Digestion, 127, 128, 137, 149, 152, 169 Digestive system, 56, 137, 143 Digestive tract, 77, 137, 167, 168 Dihydrotestosterone, 137, 164 Dihydroxy, 64, 75, 137 Dilatation, 123, 124, 137, 173 Dilatation, Pathologic, 137, 173 Dilation, 128, 137, 173 Dilator, 138, 157 Diltiazem, 44, 93, 138 Dimethyl, 59, 64, 68, 75, 138 Direct, iii, 8, 59, 63, 71, 97, 132, 138, 146, 164 Dissociation, 122, 138, 150 Diurnal, 43, 138
Dolichol, 61, 138 Dose-dependent, 17, 26, 138 Double-blind, 20, 28, 138 Doxorubicin, 36, 138 Drug Interactions, 24, 98, 138 Duodenum, 127, 138, 169 Dyes, 123, 127, 138 Dyslipidemia, 11, 29, 32, 39, 42, 108, 110, 138 E Effector, 10, 67, 78, 121, 134, 138 Efficacy, 7, 8, 13, 15, 19, 21, 22, 23, 24, 26, 29, 32, 42, 48, 66, 74, 138 Elasticity, 125, 135, 138 Elastin, 133, 138 Electrolyte, 139, 167 Electrophysiological, 13, 139 Emboli, 139, 173 Embolism, 139, 163, 174 Embolization, 139, 173 Embolus, 139, 148 Embryo, 130, 139, 148 Emergency Medicine, 89, 139 Emergency Treatment, 139 Emphysema, 81, 139 Emulsion, 15, 139, 142 Enalapril, 20, 139 Encephalitis, 10, 139 Encephalitis, Viral, 139 Encephalopathy, 67, 78, 139 Endarterectomy, 124, 139 Endogenous, 25, 65, 77, 140, 171 Endostatin, 79, 140 Endothelial cell, 17, 34, 38, 42, 140, 141 Endothelium, 17, 140, 157 Endothelium, Lymphatic, 140 Endothelium, Vascular, 140 Endothelium-derived, 140, 157 Endotoxin, 67, 78, 140, 172 Enterohepatic, 140, 169 Enterohepatic Circulation, 140, 169 Environmental Exposure, 140, 158 Environmental Health, 102, 104, 140 Enzymatic, 59, 83, 123, 129, 134, 140 Eosinophils, 140, 144, 151 Epidemiologic Studies, 5, 140 Epidemiological, 17, 66, 140 Epidermoid carcinoma, 140, 168 Epithelial, 37, 67, 78, 122, 140, 145 Epithelial Cells, 37, 67, 78, 140, 145 Epithelium, 140 Erythrocyte Volume, 128, 141
Index 179
Erythrocytes, 18, 128, 141, 166 Erythromycin, 39, 141, 165 Esophagus, 75, 137, 141, 143, 169 Estrogen, 12, 31, 141 Estrogen receptor, 12, 141 Ethanol, 141 Exocrine, 132, 141, 158 Exogenous, 65, 140, 141, 172 Expiration, 92, 141 External-beam radiation, 141, 150, 163, 174 Extracellular, 61, 123, 126, 134, 141, 142, 148, 158, 167 Extracellular Matrix, 134, 141, 142, 148, 158 F Fallopian tube, 141, 165 Family Planning, 103, 141 Fat, 3, 49, 73, 122, 125, 127, 128, 135, 139, 141, 151, 155, 157, 165, 167, 172 Fatty acids, 33, 141, 162 Feces, 132, 141, 169 Fermentation, 59, 60, 64, 68, 69, 70, 71, 72, 77, 85, 87, 141 Fibrin, 128, 141, 170, 171 Fibroblast Growth Factor, 48, 141 Fibroblasts, 33, 67, 78, 142, 149 Fibrosis, 81, 122, 142, 166 Fixation, 142, 166 Flatus, 58, 142, 143 Foam Cells, 142, 174 Fold, 13, 16, 45, 142 Food Technology, 142, 154 Forearm, 128, 142 Frameshift, 142, 172 Frameshift Mutation, 142, 172 Free Radicals, 10, 125, 138, 142, 156 Freeze Drying, 86, 142 Fungi, 124, 126, 142, 143, 154, 168, 174 Fungus, 59, 77, 85, 131, 142 G Gallate, 8, 143 Gallbladder, 121, 127, 132, 137, 143 Gallstones, 127, 131, 132, 143 Ganglia, 121, 143, 156, 159, 169 Gas, 123, 142, 143, 146, 157, 173 Gastric, 40, 130, 143 Gastroenterology, 6, 8, 143 Gastrointestinal, 126, 129, 132, 141, 143, 169 Gemfibrozil, 3, 4, 14, 19, 27, 32, 40, 41, 48, 143
Gene, 8, 15, 17, 22, 60, 76, 128, 143, 157 Gene Expression, 17, 22, 143 Genetic Code, 143, 157 Genetic Engineering, 128, 133, 143 Genetic testing, 76, 143 Genetics, 37, 136, 143 Genital, 132, 143, 165 Genotype, 18, 143, 159 Gland, 12, 135, 143, 158, 160, 162, 166, 169, 171 Glioblastoma, 20, 31, 143, 144 Glioblastoma multiforme, 20, 144 Glioma, 33, 144 Glomerular, 31, 144 Glomerulus, 144, 156 Glucocorticoid, 129, 137, 144 Glucose, 64, 126, 131, 137, 144, 145, 148, 166 Glucose Intolerance, 137, 144 Glutathione Peroxidase, 144, 166 Glycine, 123, 127, 131, 144, 157, 166 Glycols, 144, 146 Glycoproteins, 144, 148, 149 Gonadal, 144, 168 Governing Board, 144, 161 Grade, 144 Graft, 144, 146, 155 Grafting, 15, 144 Granulocytes, 144, 151, 167, 174 Granulomatous Disease, Chronic, 144, 165 Growth, 5, 7, 13, 14, 16, 29, 30, 34, 35, 37, 61, 75, 79, 93, 124, 125, 127, 130, 131, 140, 141, 145, 149, 153, 154, 156, 157, 158, 160, 162, 171, 172, 173 Growth factors, 16, 145, 154 Guanine, 61, 145, 163 Guanylate Cyclase, 145, 157 H Half-Life, 130, 145 Haptens, 122, 145 Headache, 58, 145 Headache Disorders, 145 Heart attack, 88, 130, 145 Heart failure, 124, 145, 152 Heme, 136, 145 Hemodynamics, 9, 145 Hemoglobin, 141, 145, 150, 151 Hemorrhage, 9, 135, 145, 156, 169 Hemostasis, 145, 149 Hepatic, 145, 167 Hepatocytes, 19, 145 Heredity, 121, 143, 146
180
Lovastatin
Heterodimers, 86, 146, 148 Heterogeneity, 122, 146 High-density lipoproteins, 81, 146 Histidine, 146, 149 Homogeneous, 88, 125, 146 Homologous, 146, 166, 170, 172 Hormonal, 126, 146, 159 Hormone, 135, 137, 146, 148, 161, 165, 167, 170, 171 Host, 15, 60, 79, 127, 146, 147, 173 Hybrid, 9, 146 Hybridomas, 146, 149 Hydrogen, 62, 70, 121, 123, 127, 129, 137, 144, 146, 151, 155, 157, 158, 162 Hydrogen Peroxide, 144, 146, 151 Hydrogenation, 62, 63, 146 Hydrolysis, 25, 59, 82, 146, 159 Hydrophobic, 146, 150, 151 Hydroxides, 146 Hydroxyl Radical, 67, 78, 146 Hydroxylysine, 133, 146 Hydroxyproline, 123, 133, 147 Hyperlipidaemia, 24, 32, 66, 147 Hyperlipidemia, 4, 33, 41, 44, 45, 88, 109, 138, 147 Hyperplasia, 12, 147 Hypersensitivity, 122, 147, 165, 166 Hypertension, 4, 21, 109, 123, 124, 125, 130, 139, 145, 147, 152 Hypertriglyceridemia, 138, 147 Hypertrophy, 147 Hypnotic, 127, 147, 170 I Id, 49, 108, 109, 110, 111, 116, 118, 147 Ileal, 48, 147 Ileum, 147 Imidazole, 65, 147 Immune function, 58, 147 Immune response, 124, 125, 126, 135, 145, 147, 166, 169, 173 Immune system, 125, 127, 147, 152, 155, 173, 174 Immunity, 147, 157 Immunization, 147, 161, 166 Immunocompromised, 80, 147 Immunologic, 10, 147, 164 Immunology, 11, 33, 122, 147 Immunosuppressive, 9, 136, 144, 147 Impairment, 148, 154 Implant radiation, 148, 149, 150, 164, 174 In vitro, 5, 11, 13, 15, 18, 19, 30, 35, 37, 38, 40, 60, 148, 171
In vivo, 5, 13, 15, 19, 35, 148, 169 Incision, 148, 149 Incubated, 12, 148 Indicative, 148, 159, 173 Induction, 10, 12, 16, 31, 35, 36, 66, 67, 77, 78, 148, 167 Infarction, 72, 82, 148, 165 Infection, 11, 79, 127, 128, 139, 147, 148, 152, 159, 165, 169, 174 Inhalation, 122, 126, 148, 154 Initiation, 10, 148, 169, 171 Inner ear, 130, 148 Inoculum, 64, 148 Inorganic, 65, 72, 146, 148 Insulator, 148, 155 Insulin, 73, 148, 172 Insulin-dependent diabetes mellitus, 148 Integrins, 11, 148 Interferon, 79, 149 Interferon Alfa-2b, 79, 149 Interferon-alpha, 149 Interleukin-6, 38, 149 Intermittent, 28, 53, 54, 149 Intermittent Claudication, 28, 53, 54, 149 Internal Medicine, 5, 6, 45, 143, 149 Internal radiation, 149, 150, 163, 174 Interstitial, 81, 128, 149, 150, 156, 174 Intestinal, 42, 80, 131, 132, 149 Intestinal Mucosa, 132, 149 Intestine, 75, 127, 128, 134, 140, 149, 151 Intoxication, 130, 149 Intracellular, 61, 79, 148, 149, 157, 162, 166, 167 Intrinsic, 58, 75, 122, 149 Invasive, 9, 147, 149 Ion Channels, 126, 149 Ion Exchange, 86, 131, 149 Ionization, 150 Ionizing, 33, 122, 140, 150, 164 Ions, 121, 127, 132, 138, 139, 146, 150, 155 Iridium, 62, 63, 150 Irradiation, 19, 150, 174 Ischemia, 9, 16, 67, 78, 126, 150, 155, 165 Ischemic stroke, 16, 150 Isoleucine, 61, 150 Isoprenoid, 61, 150 Isotretinoin, 8, 150 Itraconazole, 25, 150 J Joint, 6, 126, 132, 150, 158, 170 K Kb, 102, 150
Index 181
Ketoconazole, 19, 150 Kidney Disease, 56, 102, 130, 150 Kidney Transplantation, 32, 151 Kinetic, 14, 150, 151 L Labile, 82, 134, 151 Large Intestine, 134, 137, 149, 151, 164, 167 Latency, 7, 151 Latent, 151, 161 Laxative, 122, 131, 151 Lectin, 44, 151 Lens, 30, 37, 151 Lethal, 82, 151 Leucine, 61, 151 Leucocyte, 151 Leukaemia, 31, 151 Leukemia, 5, 22, 30, 31, 32, 34, 35, 43, 44, 138, 151 Leukocytes, 67, 78, 127, 128, 140, 144, 149, 151, 172 Library Services, 116, 151 Ligament, 141, 151, 162 Ligands, 148, 151 Lipid Peroxidation, 29, 151, 158 Lipopolysaccharide, 67, 78, 151 Lipoprotein, 18, 25, 27, 32, 40, 42, 45, 48, 74, 76, 138, 151, 152 Lipoprotein Lipase, 76, 152 Lisinopril, 20, 152 Lithium, 69, 71, 152 Liver, 24, 44, 74, 77, 121, 125, 127, 130, 136, 137, 139, 140, 141, 143, 145, 146, 152, 164 Localization, 61, 152 Localized, 15, 142, 148, 152, 160 Low-density lipoprotein, 22, 37, 38, 39, 44, 81, 87, 138, 152 Lubricants, 87, 152, 156 Luciferase, 8, 152 Lung metastases, 14, 152 Lupus, 8, 67, 78, 152 Lymph, 140, 152 Lymphatic, 140, 148, 152, 168 Lymphocyte, 124, 152, 153 Lymphoid, 124, 151, 152, 153 Lymphoma, 5, 34, 35, 153 M Macroglia, 153, 154 Malignant, 7, 14, 33, 35, 61, 93, 122, 125, 143, 153, 154, 164 Malignant mesothelioma, 35, 93, 153, 154 Malnutrition, 126, 129, 153 Mammary, 12, 152, 153
Manic, 152, 153 Mannans, 142, 153 Maximum Tolerated Dose, 13, 153 Meat, 74, 137, 153 Meat Products, 137, 153 Medial, 126, 153 Mediate, 67, 78, 153 Mediator, 67, 78, 132, 153 MEDLINE, 103, 153 Medulloblastoma, 22, 37, 39, 153 Melanocytes, 7, 14, 153 Melanoma, 7, 14, 36, 62, 153 Melanosomes, 153 Meninges, 130, 131, 135, 153 Meningioma, 36, 153 Meningitis, 150, 153 Menopause, 154, 161 Mental, iv, 4, 56, 102, 104, 132, 133, 138, 154, 161, 163 Mental Disorders, 56, 154, 161, 163 Mental Health, iv, 4, 56, 102, 104, 154, 161, 163 Mesothelioma, 153, 154 Metabolite, 60, 77, 85, 93, 138, 152, 154, 161 Metastasis, 38, 154 Metastatic, 7, 38, 75, 154 Methionine, 61, 138, 154, 169 Methylene Chloride, 65, 154 MI, 119, 154 Microbe, 154, 171 Microbiological, 59, 154 Microbiology, 154 Microglia, 10, 67, 78, 126, 154 Microorganism, 64, 69, 72, 133, 154, 158, 173 Microtubules, 154, 158 Migration, 14, 31, 38, 154 Mineralization, 129, 154 Mitosis, 125, 155 Mitotic, 35, 155 Modeling, 9, 155 Modification, 32, 60, 67, 78, 123, 143, 155, 163 Molecular Structure, 155, 172 Monoclonal, 146, 150, 155, 164, 174 Monocyte, 25, 155 Morphological, 139, 143, 153, 155 Mucolytic, 121, 155 Mucosa, 13, 152, 155 Multiple sclerosis, 10, 44, 66, 67, 77, 78, 89, 155
182
Lovastatin
Myelin, 155 Myeloma, 43, 155 Myocardial infarction, 74, 82, 110, 135, 154, 155, 174 Myocardial Ischemia, 24, 93, 123, 135, 155 Myocardial Reperfusion, 155, 165 Myocardial Reperfusion Injury, 155, 165 Myocardium, 124, 154, 155, 156 N Naphthalenes, 77, 156 Narcotic, 154, 156 Natriuresis, 124, 156 NCI, 1, 55, 101, 132, 156 Need, 3, 7, 49, 70, 80, 112, 122, 156, 167 Neoplasia, 12, 39, 156 Neoplastic, 146, 153, 156 Nephritis, 10, 156 Nerve, 132, 136, 153, 155, 156, 157, 161, 165, 166, 169, 172, 173 Nervous System, 12, 74, 131, 153, 156, 159, 169, 173 Neural, 123, 154, 156, 159 Neuroblastoma, 30, 156 Neurodegenerative Diseases, 67, 78, 156 Neuroectodermal tumor, 35, 156, 161 Neurologic, 144, 156 Neuronal, 9, 16, 67, 78, 156 Neurons, 67, 78, 137, 143, 156, 169, 170 Neurotoxic, 67, 78, 126, 157 Neurotoxin, 89, 157 Neurotransmitter, 121, 123, 129, 144, 149, 157, 167, 169 Neutrons, 122, 150, 157, 163 Neutrophil, 67, 78, 157 Niacin, 4, 20, 21, 32, 33, 39, 40, 48, 50, 53, 54, 89, 92, 157, 172 Nitric Oxide, 10, 12, 16, 17, 66, 67, 77, 89, 157 Nitrogen, 16, 64, 68, 69, 72, 86, 123, 136, 142, 157, 172 Nitroglycerin, 88, 89, 157 Non-small cell lung cancer, 5, 157 Nuclear, 127, 143, 157 Nucleic acid, 67, 76, 78, 136, 143, 157, 163 Nucleus, 61, 83, 125, 127, 132, 135, 136, 137, 140, 157, 162, 169 O Omega-3 fatty acid, 5, 157 Oncogene, 35, 36, 157 Oncogenic, 149, 158, 162, 163 Opacity, 137, 158 Organ Culture, 158, 171
Organelles, 136, 153, 158 Osteoarthritis, 67, 78, 158 Osteoblasts, 15, 158 Osteoporosis, 108, 158 Outpatient, 25, 158 Ovaries, 158, 165 Oxidation, 28, 38, 45, 67, 78, 121, 125, 136, 144, 151, 158 Oxidative Stress, 18, 158 P Paclitaxel, 43, 158 Palliative, 158, 170 Pancreas, 121, 137, 143, 148, 158 Pancreatic, 36, 60, 62, 130, 132, 158 Pancreatic cancer, 36, 158 Paroxysmal, 123, 145, 158 Partial remission, 158, 164 Pathogen, 148, 158 Pathogenesis, 11, 17, 67, 78, 159 Pathologic, 125, 135, 147, 159 Pathologic Processes, 125, 159 Pathophysiology, 9, 10, 16, 159 Patient Compliance, 4, 159 Patient Education, 4, 114, 116, 119, 159 Pelvic, 159, 162 Penicillin, 123, 124, 159 Penis, 159, 165 Peptide, 40, 45, 123, 132, 141, 159, 162 Periodicity, 43, 159 Peripheral Nervous System, 156, 157, 159, 169 Perivascular, 154, 159 Petrolatum, 139, 159 Phagocytosis, 154, 159 Pharmacokinetic, 20, 159 Pharmacologic, 12, 145, 159, 171 Phenolphthalein, 139, 159 Phenotype, 17, 32, 43, 159 Phenyl, 70, 159 Phenylacetate, 10, 13, 33, 159 Phospholipases, 159, 167 Phospholipids, 141, 151, 160 Phosphorus, 129, 160 Phosphorylated, 133, 160 Phosphorylation, 6, 15, 35, 36, 160 Physiologic, 145, 160, 162, 164 Physiology, 6, 9, 17, 139, 143, 160 Pilot study, 5, 28, 160 Pituitary Gland, 141, 160 Plants, 132, 144, 151, 160, 166, 168, 171, 172, 173 Plaque, 34, 89, 124, 160
Index 183
Plasma cells, 43, 124, 155, 160 Platelet Activation, 160, 167 Platelet Aggregation, 67, 78, 89, 157, 160 Platelets, 42, 89, 157, 160, 170, 171 Pneumonia, 135, 160 Pneumonitis, 81, 160 Polymers, 15, 160, 162 Polyposis, 134, 160 Postmenopausal, 31, 158, 161 Postprandial, 24, 161 Postsynaptic, 161, 167 Potentiates, 12, 19, 29, 36, 92, 161 Potentiation, 161, 167 Practice Guidelines, 104, 108, 161 Precancerous, 131, 161 Preclinical, 8, 76, 161 Precursor, 49, 89, 125, 136, 138, 140, 161, 172 Predisposition, 76, 161 Premalignant, 7, 161 Prevalence, 4, 6, 161 Primary Prevention, 45, 110, 161 Primitive neuroectodermal tumors, 153, 161 Progesterone, 161, 168 Progression, 6, 10, 11, 13, 26, 28, 61, 124, 161 Progressive, 12, 125, 130, 145, 156, 158, 160, 161, 172 Proline, 133, 147, 161 Prophylaxis, 73, 162, 173 Prostaglandin, 124, 162 Prostate, 12, 38, 75, 162, 165 Prostate gland, 12, 162 Prostatic Hyperplasia, 12, 162 Protease, 134, 162 Protein C, 123, 125, 127, 151, 162 Protein S, 15, 35, 67, 78, 128, 141, 143, 162, 169 Protocol, 7, 162 Protons, 122, 146, 150, 162, 163 Proto-Oncogene Proteins, 158, 162 Proto-Oncogene Proteins c-mos, 158, 162 Protozoa, 154, 163, 168 Pruritus, 58, 163 Psychiatric, 74, 154, 163 Psychiatry, 30, 41, 142, 163 Psychic, 154, 163, 166 Psychosine, 12, 163 Public Health, 6, 12, 14, 104, 163 Public Policy, 103, 163 Pulmonary, 75, 81, 128, 134, 163, 173
Pulmonary Artery, 128, 163 Pulmonary Embolism, 163, 173 Purifying, 84, 163 Purines, 163, 166 Pyrimidines, 163, 166 Q Quality of Life, 18, 81, 163 R Race, 154, 163 Radiation, 33, 124, 140, 141, 142, 149, 150, 163, 164, 174 Radiation therapy, 141, 149, 150, 163, 174 Radioactive, 145, 146, 148, 149, 150, 157, 158, 163, 164, 174 Radioisotope, 141, 164, 171 Radiolabeled, 150, 164, 174 Radiotherapy, 128, 150, 164, 174 Randomized, 5, 12, 14, 20, 29, 41, 138, 164 Reactive Oxygen Species, 67, 78, 164 Reagent, 152, 164 Receptor, 11, 29, 34, 44, 45, 61, 80, 124, 164, 167 Recombinant, 149, 164, 173 Rectum, 125, 128, 133, 134, 137, 142, 143, 151, 162, 164 Recur, 159, 164 Recurrence, 80, 131, 159, 164 Refer, 1, 129, 134, 142, 152, 157, 164, 171 Refractory, 75, 164 Regeneration, 141, 164 Regimen, 8, 66, 138, 159, 164 Remission, 10, 164 Renin, 124, 164 Renin-Angiotensin System, 124, 164 Reperfusion, 9, 16, 67, 78, 155, 156, 165 Reperfusion Injury, 16, 165 Reproductive system, 12, 162, 165 Respiratory Burst, 67, 78, 165 Respiratory distress syndrome, 81, 165 Resuscitation, 139, 165 Retina, 151, 165 Reversion, 165, 172 Rheumatism, 165 Rheumatoid, 8, 67, 78, 165 Rheumatoid arthritis, 8, 67, 78, 165 Risk factor, 6, 45, 58, 64, 65, 70, 74, 75, 86, 109, 140, 165 Risk patient, 7, 89, 165 Rod, 127, 165 Roxithromycin, 27, 165 S Salivary, 137, 158, 166
184
Lovastatin
Salivary glands, 137, 166 Saphenous, 20, 42, 166 Saphenous Vein, 20, 42, 166 Saponins, 166, 168 Sclerosis, 67, 78, 125, 126, 155, 166 Screening, 53, 109, 110, 133, 166 Secretion, 48, 121, 148, 154, 166 Sedentary, 65, 166 Seizures, 144, 158, 166 Selenium, 79, 166 Semen, 162, 166 Senile, 34, 158, 166 Sensitization, 33, 166 Septic, 66, 67, 77, 166 Serine, 61, 163, 166 Serous, 140, 166 Serum, 4, 27, 29, 45, 49, 66, 77, 83, 93, 134, 143, 152, 166, 172 Shock, 66, 67, 77, 166 Side effect, 12, 58, 66, 74, 82, 97, 122, 127, 136, 166, 169, 171 Signal Transduction, 17, 44, 61, 167 Signs and Symptoms, 164, 167 Skeleton, 64, 121, 150, 162, 167 Skull, 135, 167, 170 Small cell lung cancer, 167 Small intestine, 131, 132, 138, 146, 147, 149, 167 Smoking Cessation, 21, 167 Smooth muscle, 20, 35, 37, 41, 42, 44, 48, 67, 78, 122, 142, 157, 165, 167, 169 Social Environment, 163, 167 Social Welfare, 21, 167 Sodium, 10, 13, 16, 33, 66, 77, 85, 86, 156, 167 Soft tissue, 128, 167 Solid tumor, 124, 138, 140, 168 Solvent, 62, 63, 65, 84, 141, 154, 168 Specialist, 111, 138, 168 Species, 15, 16, 60, 71, 83, 84, 85, 87, 146, 154, 155, 163, 164, 168, 169, 173, 174 Specificity, 122, 168 Spectrum, 150, 154, 165, 168 Spinal cord, 126, 131, 132, 153, 156, 159, 168, 169 Sporadic, 156, 168 Spores, 148, 168 Squamous, 25, 29, 39, 60, 140, 157, 168 Squamous cell carcinoma, 25, 29, 39, 140, 157, 168 Squamous cells, 168 Stabilization, 89, 168
Statistically significant, 14, 168 Steady state, 64, 168 Sterility, 136, 168 Steroid, 64, 127, 135, 166, 167, 168 Stimulus, 134, 149, 151, 169, 170 Stomach, 75, 121, 137, 141, 143, 146, 167, 169 Stool, 133, 151, 169 Strand, 67, 78, 169 Streptomycin, 80, 169 Stress, 17, 65, 158, 161, 165, 169 Stroke, 9, 16, 56, 67, 78, 89, 102, 108, 130, 150, 169 Subacute, 148, 169 Subarachnoid, 145, 169 Subclinical, 148, 166, 169 Subcutaneous, 15, 169 Sublingual, 88, 169 Subspecies, 168, 169 Substance P, 141, 154, 166, 169 Substrate, 15, 61, 62, 63, 169 Sulfur, 154, 169 Sulindac, 92, 169 Superoxide, 67, 78, 165, 169 Supplementation, 28, 45, 169 Suppression, 41, 89, 169 Sympathetic Nervous System, 124, 169 Symphysis, 131, 162, 170 Symptomatic, 53, 170 Synaptic, 157, 167, 170 Synergistic, 13, 43, 73, 89, 170 Systemic, 8, 82, 98, 128, 145, 148, 150, 164, 170, 174 Systolic, 147, 170 T Tachycardia, 126, 170 Tachypnea, 126, 170 Taurine, 127, 131, 170 Temporal, 9, 17, 145, 170 Teratogenic, 14, 138, 150, 170 Testicular, 12, 170 Testis, 170 Testosterone, 164, 170 Thalidomide, 79, 170 Therapeutics, 5, 19, 20, 24, 29, 30, 38, 40, 41, 42, 43, 44, 48, 87, 98, 170 Threonine, 163, 166, 170 Threshold, 147, 170 Thrombin, 141, 160, 162, 170 Thrombocytes, 160, 170 Thrombosis, 25, 28, 34, 87, 149, 162, 169, 170
Index 185
Thrombus, 89, 135, 148, 150, 155, 160, 171, 173 Thyroid, 35, 37, 91, 130, 171 Thyroid Gland, 171 Thyroxine, 4, 171 Tissue Culture, 14, 171 Topical, 8, 133, 141, 146, 150, 156, 159, 171 Torsion, 148, 171 Toxic, iv, 7, 64, 66, 67, 78, 89, 130, 136, 140, 147, 166, 171 Toxicity, 7, 8, 39, 61, 67, 76, 78, 138, 153, 171 Toxicology, 31, 104, 171 Toxin, 130, 140, 171 Tracer, 45, 171 Trachea, 129, 171 Transcription Factors, 62, 171 Transduction, 17, 167, 171 Transfection, 128, 171 Transferases, 61, 171 Translation, 123, 141, 171 Translational, 5, 9, 172 Translocate, 62, 172 Translocation, 141, 172 Transmitter, 121, 126, 149, 153, 172 Tricyclic, 43, 172 Triglyceride, 133, 147, 172 Troglitazone, 73, 172 Tryptophan, 133, 172 Tumor Necrosis Factor, 170, 172 Tumour, 172, 174 Tunica, 139, 155, 172 Type 2 diabetes, 29, 42, 172 Typhimurium, 80, 172 U Ubiquinone, 45, 61, 172 Unconscious, 136, 147, 172 Univalent, 146, 158, 172 Urethra, 159, 162, 172 Urinary, 41, 130, 132, 172
Urinary tract, 130, 172 Urine, 128, 156, 172 Uterus, 131, 158, 161, 165, 172, 173 V Vaccine, 162, 173 Vagina, 131, 137, 165, 173 Vasoconstriction, 89, 173 Vasodilation, 31, 67, 78, 89, 124, 173 Vasodilators, 157, 173 Vasomotor, 12, 173 VE, 49, 173 Vector, 171, 173 Vegetative, 128, 173 Vein, 14, 123, 157, 166, 173 Venous, 157, 162, 173 Venous Thrombosis, 173 Venules, 128, 129, 140, 173 Veterinary Medicine, 103, 173 Viral, 121, 139, 158, 171, 173 Virulence, 171, 173 Virus, 11, 18, 127, 131, 143, 149, 160, 171, 173 Viscosity, 121, 173 Vitreous, 151, 165, 173 Vitro, 11, 15, 18, 173 Vivo, 15, 18, 45, 173 W Warfarin, 28, 173 White blood cell, 124, 148, 151, 152, 155, 157, 160, 174 Windpipe, 171, 174 Womb, 165, 172, 174 Wound Healing, 141, 149, 174 X Xanthoma, 73, 174 Xenograft, 124, 174 X-ray, 14, 150, 157, 163, 164, 174 X-ray therapy, 150, 174 Y Yeasts, 142, 159, 174
186
Lovastatin
Index 187
188
Lovastatin
