Indomethacin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

INDOMETHACIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES ...

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INDOMETHACIN 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., 1960Indomethacin: 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: 0-597-84463-1 1. Indomethacin-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 indomethacin. 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 INDOMETHACIN ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Indomethacin................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 30 The National Library of Medicine: PubMed ................................................................................ 31 CHAPTER 2. NUTRITION AND INDOMETHACIN .............................................................................. 71 Overview...................................................................................................................................... 71 Finding Nutrition Studies on Indomethacin ............................................................................... 71 Federal Resources on Nutrition ................................................................................................... 73 Additional Web Resources ........................................................................................................... 73 CHAPTER 3. DISSERTATIONS ON INDOMETHACIN ......................................................................... 75 Overview...................................................................................................................................... 75 Dissertations on Indomethacin .................................................................................................... 75 Keeping Current .......................................................................................................................... 76 CHAPTER 4. CLINICAL TRIALS AND INDOMETHACIN .................................................................... 77 Overview...................................................................................................................................... 77 Recent Trials on Indomethacin .................................................................................................... 77 Keeping Current on Clinical Trials ............................................................................................. 78 CHAPTER 5. PATENTS ON INDOMETHACIN .................................................................................... 81 Overview...................................................................................................................................... 81 Patents on Indomethacin.............................................................................................................. 81 Patent Applications on Indomethacin........................................................................................ 105 Keeping Current ........................................................................................................................ 108 CHAPTER 6. PERIODICALS AND NEWS ON INDOMETHACIN ........................................................ 109 Overview.................................................................................................................................... 109 News Services and Press Releases.............................................................................................. 109 Newsletter Articles .................................................................................................................... 112 Academic Periodicals covering Indomethacin............................................................................ 113 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 115 Overview.................................................................................................................................... 115 U.S. Pharmacopeia..................................................................................................................... 115 Commercial Databases ............................................................................................................... 116 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 119 Overview.................................................................................................................................... 119 NIH Guidelines.......................................................................................................................... 119 NIH Databases........................................................................................................................... 121 Other Commercial Databases..................................................................................................... 123 APPENDIX B. PATIENT RESOURCES ............................................................................................... 125 Overview.................................................................................................................................... 125 Patient Guideline Sources.......................................................................................................... 125 Finding Associations.................................................................................................................. 127 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 129 Overview.................................................................................................................................... 129 Preparation................................................................................................................................. 129 Finding a Local Medical Library................................................................................................ 129 Medical Libraries in the U.S. and Canada ................................................................................. 129 ONLINE GLOSSARIES................................................................................................................ 135 Online Dictionary Directories ................................................................................................... 136

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INDOMETHACIN DICTIONARY............................................................................................. 139 INDEX .............................................................................................................................................. 217

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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 indomethacin 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 indomethacin, 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 indomethacin, 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 indomethacin. 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 indomethacin, 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 indomethacin. 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 INDOMETHACIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on indomethacin.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and indomethacin, 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 “indomethacin” (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: •

Indomethacin-Induced Behavioral Changes in an Elderly Patient With Dementia Source: Annals of Pharmacotherapy. 32: 201-203. February 1998. Summary: This journal article presents a case report of behavioral changes induced by indomethacin in a 92-year-old white man with Alzheimer's disease. The patient, who had a history of dementia, glaucoma, and constipation, was treated with indomethacin for an episode of pseudogout. After six doses of indomethacin 25 mg, the patient became very agitated and confused, and was physically and verbally abusive to the nurses. The indomethacin was discontinued, and the patient recovered after treatment with haloperidol 0.5 mg/d for 10 days. Only a few other cases of indomethacin-related psychosis have been reported in the literature. Health care providers should be aware that patients with dementia who are receiving indomethacin may be at risk of

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developing severe behavior problems in addition to gastrointestinal and renal adverse effects. 10 references. (AA-M). •

Colchicine and Indomethacin for the Treatment of Relapsing Polychondritis Source: Journal of the American Academy of Dermatology. 46(2): S22-S24. February 2002. Summary: This journal article provides health professionals with information on the effectiveness of oral colchicine and indomethacin in the maintenance phase of treatment of relapsing polychondritis. This chronic, multisystem, potentially life threatening disease is characterized by recurring bouts of inflammation in cartilaginous tissues. The article presents the case of a 63 year old man who presented to a medical facility for evaluation. On physical examination, the man had a hoarse and nasally congested voice, a saddle shaped nose, and bilateral erythematous, tender plaques involving the pinna of the ears and sparing the lobes. The man was treated with 40 milligrams (mg) of prednisone per day and his symptoms cleared. On more than one occasion, he was unable to tolerate tapering of the prednisone below 10 to 20 mg per day. Azathioprine was first added. Following a flare, azathioprine was discontinued. Colchicine and then indomethacin were added to the treatment regimen. Following the addition of these drugs, the minimum tolerable dosage of prednisone decreased significantly. The article discusses the pathophysiology of relapsing polychondritis and proposes that colchicine and indomethacin be considered as steroid sparing agents that may lengthen the intercritical periods between outbreaks and decrease their severity. 3 figures and 30 references. (AA-M).

Federally Funded Research on Indomethacin The U.S. Government supports a variety of research studies relating to indomethacin. 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 indomethacin. 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 indomethacin. The following is typical of the type of information found when searching the CRISP database for indomethacin: •

Project Title: ANTI-INFLAMMATORY CONSTITUENTS

PROPERTIES

OF

CANNABIS

Principal Investigator & Institution: Zurier, Robert B.; Professor; Rheumatology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

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Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The overall long term objective of this proposal is to determine whether individual nonpsychoactive constituents of Cannabis sativa (marijuana), alone or in combination, will provide safe, effective treatment for diseases characterized by acute and/or chronic inflammation. The medicinal use of marijuana has been limited by its psychoactivity and by induction of tolerance. Existence of nonpsychoactive marijuana constituents and development of synthetic cannabinoids encourage further research to identify nonpsychoactive plant components with antiinflammatory properties. A complete marijuana extract (CME) and pure nonpsychoactive cannabinoid and noncannabinoid Cannabis constituents will be tested in human whole blood models for their ability to influence production in vitro of inflammatory eicosanoids and cytokines. The antiinflammatory effects of oral administration of the CME and the pure nonpsychoactive Cannabis constituents will also be tested in a model of acute inflammation (induced by IL-1Beta and TNFalpha in a subcutaneous air pouch in rats), and a model of chronic inflammation (adjuvant induced polyarthritis in rats). Controls for experiments in vitro and studies in animals will include vehicle, dexamethasone, indomethacin, and a selective inhibitor of cyclooxygenase 2. A noncannabinoid, nonpsychoactive marijuana constituent termed cannflavin will be isolated using high-pressure liquid chromatography and tested in the in vivo models and in vitro systems. Successful completion of the proposed experiments should identify ways of harnessing important antiinflammatory properties of marijuana without the limiting adverse effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDUCED PD

ANTI-INFLAMMATORY

THERAPIES

NEUROTOXICALLY

Principal Investigator & Institution: Isacson, Ole; Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Taken from the Investigator's Abstract) A recent large Parkinson's Disease (PD) twin study indicates that environmental and toxic factors play major roles in causing typical PD (Tanner, et. al. JAMA, 1999). Interestingly, neuroinflammation seen in the caudate-putamen is a part of the pathophysiology (Brooks, 1999). The progressive decline of dopamine (DA) terminals seen in idiopathic PD can be closely modeled in Macaca fascicularis by low-dose exposure to the mitochondrial toxin, MPTP, over nine to fourteen months. The investigators demonstrated by PET imaging of DA terminal and MRS that such primates provide a physiological chart of degeneration and appearance of PD signs (Brownell, et. al., Nat. Med., 1998). This data profile enables the design of an experimental paradigm for realistically determining toxicity, neuroinflammation and neuroprotection in idiopathic PD. In this project using the PD primate model, the investigators now propose to examine neuroprotection of the dopaminergic system by anti-inflammatory agents. Based on several studies, they hypothesize that a cyclooxygenase (COX) 1 and 2 inhibitor (indomethacin [1-(4chlorobenzoyl)-5-methoxy-2-methyl-1-H-indole-3-acetic acid]) can decrease inflammatory reactions caused by MPP+ toxicity and also reduce chronic neurodegenerative processes. In the non-human primate, a slow progressive lesion of the nigrostriatal dopaminergic system follows repeated MPTP treatment. Using PET scanning with a receptor ligand for the peripheral benzodiazepine receptor site (11-CPK1 1195), preliminary experiments indicate that they can visualize the neuroinflammatory reactions during CNS DA degeneration (as determined by 11-C-

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CFT). These measurements will be combined with MRI and MRS studies of lactate and choline as in vivo biomarkers for the glial inflammatory and toxic responses of the nigrostriatal system. As a therapy, during and after neurotoxic exposure to MPTP, the investigators will treat the PD primates with a COX I and 2 inhibitor to evaluate antiinflammatory prevention of onset and continued degeneration. Protection of the dopaminergic system by anti-inflammatory agents would be of tremendous therapeutic value for PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOTRANSPORTERS OF ENTEROBACTERIACEAE Principal Investigator & Institution: Nataro, James P.; Professor of Pediatrics; Pediatrics; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BILIARY AND INTESTINAL CELL MODELS OF DRUG TOXICITY Principal Investigator & Institution: Kanz, Mary F.; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Recent, unprecedented expansion of candidate drugs has generated a critical need for early phase toxicity testing by in vitro assays that are rapid, sensitive, reproducible and cost effective There is a particular need for cytotoxicity assays that monitor injury to cholangiocytes, epithelial cells of bile ducts (BDC), or to enterocytes, epithelial cells of the small intestine (IEC). Although these sites are known targets of widely used anticancer drugs, in vitro assays have not been established due to the lack of appropriate cell systems The goal of the proposed research is to develop cytotoxicity assays using newly available cell systems and bile from drugtreated animals as a physiologically relevant way to expose the cells to reactive drug/metabolites, which is the most plausible route of exposure. The anticancer drugs [Iomustine (CCNU), methotrexate (MTX), docetaxel (DCT)] chosen to validate these in vitro cytotoxicity models have well-established toxicities to BDC or IEC in vivo, represent classes of drugs that work by different mechanisms, and are extensively excreted in bile. Our approach is based on preliminary studies indicating that bile from rats treated with the cholangiodestructive agent 4,4'-diaminodiphenylmethane (DAPM) is cytotoxic to primary rat BDC in vitro. Functional and morphological characteristics of DAPM-induced injury to bile ducts in vivo are virtually identical to the BDC injury produced in vitro. Bile from rats treated with the NSAID indomethacin has been reported to injure a rat intestinal cell line in vitro. A more differentiated cell line that forms villus-like enterocytes (Cdx-IEC-6 cells) is proposed as the model IEC system in this application. Our specific aims are (1) validate the target organ specificity of biliary drug/ metabolites to BDC versus IEC in vitro by viability assays and functional indices of cell injury, (2) characterize the specificity, reproducibility and high-throughput possibilities of sensitive assays for mitochondrial injury, paracellular permeability, ATP content, and membrane leakage as potential biomarkers of biliary drug/ metaboliteinduced dysfunction, and (3) determine if biliary drug/metabolites induce comparable early effects on gene expression in BDC and IEC in vivo versus in vitro using laser capture microdissection and gene chip analyses. The basic techniques developed in this

Studies

7

research will lead to new methods for screening potential drug injury to target sites that are not easily investigated in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLON CANCER CHEMOPREVENTIVE AGENTS AND APOPTOSIS Principal Investigator & Institution: Giardina, Charles A.; Associate Professor; Molecular and Cell Biology; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, Ct 06269 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYCLOOXYGENASE 2 AND ALCOHOLIC LIVER DISEASE Principal Investigator & Institution: Nanji, Amin A.; Director; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 17-SEP-2001; Project End 31-AUG-2004 Summary: Conventional treatment options for alcoholic liver disease have, in general, not been successful either in reversing liver injury or preventing progression in patients who continue to abuse alcohol. Current understanding of alcoholic liver injury revolves around the roles of endotoxin and oxidative stress. These stimuli acting in concert lead to upregulation of cyclooxygenase-2 (Cox-2). Based on studies in Cox-2 deficient mice and the intragastric feeding rat model for alcoholic liver disease, induction of Cox-2 appears to be a final common pathway for alcoholic liver injury. The studies proposed will evaluate the role of Cox-1 and Cox-2 in alcoholic liver injury and test the role of specific Cox inhibitors in preventing and reversing established alcohol-induced liver injury. A specific Cox-2 inhibitor and a non-specific Cox inhibitor (indomethacin) will be administered to rats fed ethanol intragastrically and their effects on the development of pathological changes, endotoxin levels, lipid peroxidation and cytokines will be evaluated. Based on our preliminary studies that show that Indomethacin aggravates liver injury, another drug with higher Cox-2 selectivity (Meloxicam) will be used in the prevention/treatment studies. Additionally, the effects of the drugs will be tested in a model (CCI4) in which extensive fibrosis is seen. The effect of the Cox inhibitors (Cox-2 and Meloxicam) in reversing established alcoholic liver injury will also be tested in rats by simulating an in-hospital alcoholic hepatitis setting and an outpatient alcoholic liver disease setting. In the first set of experiments (in-hospital model), rats will be fed a fish oil- ethanol diet for 6 weeks to induce liver injury. After discontinuing ethanol, the Cox2 inhibitor or Meloxicam will be administered for two weeks with fish oil and dextrose. In the outpatient model, rats will be fed the fish oil-ethanol diet for 6 weeks followed by two weeks of treatment with the Cox-2 inhibitor or Meloxicam with continued ethanol administration. In both models, reversal of inflammatory and fibrotic changes will be evaluated. The prevention and treatment of alcoholic liver injury by Cox-2 inhibitors in these experiments should provide data for the testing of these drugs in patients with alcoholic liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DEOXYGUANOSIN 8 YL N ACETYLBENZIDINE FORMATION BY PEROXIDATIVE METABOLISM Principal Investigator & Institution: Lakshmi, v; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130

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Indomethacin

Timing: Fiscal Year 2002 Summary: N'-(3'-Monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is thought to play an important role in initiation of benzidine-induced bladder cancer in humans. This report assesses the possible formation of this adduct by peroxidatic activation of N-acetylbenzidine (ABZ). Adduct formation was measured by 32Ppostlabeling. Ram seminal vesicle microsomes were used as a source of prostaglandin H synthase (PHS). The peroxidatic activity of PHS was compared to that for horseradish peroxidase. Both peroxidases converted ABZ to dGp-ABZ whether DNA or 2'deoxyguanosine 3'-monophosphate (dGp) was present. Following 32P-postlabeling, the enzymatic and synthetic adduct were extracted from PEI-cellulose plates and shown to have the same HPLC elution profiles for the bisphosphate adduct (32P-dpGp-ABZ). Treatment of the enzymatic and synthetic bisphosphate adduct with nuclease P1 yielded a product which eluted at the same time from the HPLC (32P-dpG-ABZ). Additional experiment s demonstrated that the PHS-derived 5'-monophosphate (dpG-ABZ ) and 3'monophosphate (dGp-ABZ) adducts were also identical to their corresponding synthetic standard. With comparable amounts of total ABZ metabolism, PHS produced about 40fold more dGp-ABZ than horseradish peroxidase (1943 + 339 vs 49 + 7.8 fmol/mg dGp). Adduct formation was dependent upon the presence of peroxidase and the specific substrate, i.e., arachidonic acid or H2O2. Adduct formation by PHS was inhibited by indomethacin (0.1 mM), ascorbic acid (1 mM) and glutathione (10 mM), but not by DMPO (100 mM), a radical scavenger. Horseradish peroxidase adduct formation was also inhibited by ascorbic acid and glutathione. In addition, DMPO elicited greater than a 96% inhibition. Results demonstrate peroxidatic metabolism of ABZ to form dGp-ABZ. The mechanism of dGp-ABZ formation by PHS and horseradish peroxidase may be different. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINING THERAPEUTIC EFFICACY OF AGE IN AD Principal Investigator & Institution: Chauhan, Neelima B.; Assistant Professor; Anesthesiology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Based on the fact that genesis of A-beta derived from amyloidogenic processing of APP is a key event in Alzheimer's pathogenesis including inflammation, and that cholesterol homeostasis and cholinergic system regulate APP processing, current Alzheimer's therapy targets cholinergic enhancement [Tacrine, Aricept/Donezepil, Rivastigmine, Galantamine]; and regulation of inflammation by NSAIDs [Aspirin, Ibuprofen, Indomethacin]; COX-2 inhibitors [Celebrex, Vioxx]. These drugs exert serious side effects including gastrointestinal bleeding, liver and renal toxicity, nausea, and are not effective with patients carrying ApoE gene 1. Current investigational drugs include Xanthine derivativesPropentofylline and cholesterol-lowering agents [HMG-CoA reductase inhibitorsStatins]. Although some statins are shown to be anti-amyloidogenic, few clinical trials with statins are non-conclusive due to their proinflammatory nature/39. In this respect, natural alternative(s) with pleiotropic useful properties and with least adverse effects may provide greater therapeutic benefit over single-ingredient synthetic pharmaceutical drugs having serious side effects. One such alternative is garlic. Aged garlic extract (AGE) contains multipotent phytochemicals. S-Allyl-Cystein (SAC) component of AGE inhibits NFkAPPAB, TNFalpha, IL-1Beta 3, 20, and iNOS/24. Our preliminary data show that AGE reduced TNFalpha and IL-1Beta in Tg2576 in a dose-dependent manner. SAC and Diallyl disulfide (DADS) components of AGE are natural HMG-CoA reductase

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9

inhibitors 34/46. Our preliminary data show that AGE reduced cerebral amyloid in AIzheimer's transqenic model (Tg2576). In addition, AGE is known to be free-radical scavenger that enhances anti-oxidant enzymes (SOD, catalase and glutathione reductase) 3, inhibits lipid peroxidation 20, inhibits A-beta-induced apoptosis and improves memory deficits in senescence-accelerated mice. Thus, AGE is a natural "NSAID, Statin, anti-oxidant and anti-apoptotic agent"-a combination of many singleingredient synthetic pharmaceutical drugs currently used for Alzheimer's therapy. However, the validity of AGE as Alzheimer's therapy has not been explored. This project is to determine pleiotropic effects of AGE in Alzheimer's Swedish double mutant (K670M/N671L) model (Tg2576). Hypothesis: Multi-potent natural alternative AGE will prevent or reverse AD-like pathology and ameliorate behavioral deficits in Tg2576. Specific Aims: [1] Determine if dietary AGE will promote non-amyloidogenic processing and reduce pre-existing amyloid burden in Tg2576; [2] Determine if dietary AGE will attenuate A-beta-induced inflammatory cascade in Tg2576; [3] Determine if dietary AGE will inhibit apoptosis in Tg2576; [4] Determine if dietary AGE will improve hippocampal-based Morris Water Maze performance in Tg2576. Significance: Current AD-treatment utilizing cholinergic enhancers and NSAIDs is limited due to their adverse side effects and do not modify the disease process. If successful, this project will validate the use of safe, naturally well-tolerated, cost-effective and alternative herbal pharmacotherapy for treating AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF POTENT YET SAFER ANTI-INFLAMMATORY AGENTS: VIA MUTUAL PRODRUG APPR Principal Investigator & Institution: Mclean, Hugh M.; Hampton University E Queen & Tyler Sts Hampton, Va 23668 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Chronic inflammatory diseases affect approximately 10% of the U.S. population. Although both anti-inflammatory steroids (glucocorticoids) and non-steroidal antiinflammatory drugs (NSAIDS) are routinely used to provide palliative therapy for many of these maladies, there is still a distinct paucity of "safe" and effective drugs, particularly for long term therapy of many inflammatory diseases such as asthma, psoriasis, ulcerative colitis and rheumatoid arthritis. Glucocorticoids are usually considered to be the drugs par excellence for relieving inflammatory symptoms, however their therapeutic use is restricted due to their propensity to elicit potentially serious adverse effects, particularly their suppressive effects on pituitary function and the immune system. The main thrust of the proposed study is the development of antiinflammatory steroids with diminished penchant to elicit untoward systemic effects, via the mutual prodrug approach. To this end, the primary strategy is to incorporate a metabolically labile moiety, a carboxylic acid ester, into the steroid molecule (prednisolone), which would undergo facile systemic biotransformation to the less active and more readily excretable steroidal carboxylic acid. Such steroid acid esters have been dubbed antedrugs. To further enhance the topical potency and local/systemic activity ratios of these antedrugs, they will be conjugated via an ester linkage to selected NSAIDS (such as ibuprofen and indomethacin) at the 21-position of the glucocorticoids. Conjugates such as these have been dubbed mutual prodrugs, primarily because it is conceivable that upon administration, they would be biotransformed into the glucocorticoid and the NSAID, both of which could conceivably exhibit synergistic antiinflammatory activity. The results of these studies should establish axiomatically if the

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Indomethacin

conjugation of glucocorticoids that are "antedrugs", and NSAIDS, is a fundamentally sound synthetic ploy in the development of potent yet safer anti-inflammatory steroids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF INTESTINAL TRANSPORTERS ON BIOAVAILABILITY OF DIURETIC FUROSEMIDE Principal Investigator & Institution: Benet, Leslie; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 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: EFFECT PROSTAGLANDIN

OF

INTRALIPID

&

INDOMETHACIN

ON

Principal Investigator & Institution: Haastrup, Adetola; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EICOSANOIDS IN FOCAL SEGMENTAL GLOMERULOSCLEROSIS Principal Investigator & Institution: Mccarthy, Ellen T.; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 25-AUG-1998; Project End 30-JUN-2004 Summary: (adapted from the application) Focal segmental glomerulosclerosis (FSGS) is a renal disease of unknown etiology characterized by heavy proteinuria, hypertension, and progression to renal failure. The incidence of FSGS has increased by up to 8-fold in the past 20 years. It is the now the most common progressive glomerular disease in children and account for 20_25% of nephrotic syndrome in adults. Cyclooxygenase (COX) inhibitors decrease proteinuria in many proteinuric glomerular disease, including FSGS. The applicant has participated in studies that document the presence of a plasma factor in patients with FSGS which causes an increase in glomerular albumin permeability. In preliminary studies, she has shown that the COX inhibitor indomethacin prevented the increased in albumin permeability caused by the FSGS factor, thus implicating eicosanoids of the COX pathways of arachidonic acid metabolism as mediators of this effect. In the proposed studies, she will determine the role of these eicosanoids in mediating the increased glomerular protein permeability caused by the FSGS factor, and explore mechanisms by which this factor regulated synthesis of COX-derived eicosanoids. Hypothesis to be tested are: (1) the FSGS factor increased synthesis of specific eicosanoids of the COX pathway, and these eicosanoids increase glomerular albumin permeability; (2) the FSGS factor increases synthesis of COX-derived eicosanoids via an effect on activity and/or expression of phospholipase A2 (PLA2), constitutive COX or inducible COX. She will measure eicosanoid production by isolated glomeruli or cultured glomerular cells after incubation with the FSGS factor and will then determine the effect of eicosanoids identified in these studies, on glomerular albumin permeability. Finally, she will investigate the mechanism by which the FSGS factor enhance eicosanoid synthesis by measuring activity and expression (mRNA and protein) of PLA, and of constitutive and inducible COX in glomeruli and in

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cultured glomerular cells. The proposed project is expected to provide the applicant with valuable opportunities to expand hew knowledge and expertise in experimental design, investigative techniques, and data analysis. Results of these studies will provide insight into the pathophysiology of FSGS. Additionally, they may lead to a better understanding of the general mechanism by which proteinuria develops and thus point to interventions that may alleviate or prevent proteinuria in FSGS and in other glomerular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPERIMENTAL MODEL PREMATURITY

FOR CHORIOAMNIONITIS

AND

Principal Investigator & Institution: Gravett, Michael G.; Chief; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAY-2006 Summary: Prematurity is the leading cause of neonatal morbidity and mortality in the United States. Intrauterine infections are an important, and potentially treatable cause of prematurity, and are associated with increased risk of neonatal white matter lesions of the brain and cerebral palsy. However, the mechanisms by which infection leads to prematurity and/or cerebral palsy remain speculative and treatment strategies untested largely because humans cannot be longitudinally studied following infection. We propose to use chronically instrumented pregnant rhesus monkeys at 120-130 day gestation with experimental intrauterine infection, as previously described (Gravett et al, Am J Obstet and Gynecol; 171:1660-1667,1994) to study the temporal and quantitative relationships among infection, cytokines, prostaglandins, steroid hormones, cytokine antagonists, preterm labor, and neonatal white matter lesions of the brain in order to develop effective interventional strategies. After postoperative stabilization in a tether, we will; (1) inoculate Group B Streptococci (GBS) into the amniotic fluid to establish intrauterine infection and preterm labor. Uterine contractility will be continuously monitored and periodic samples of amniotic fluid and maternal and fetal blood (1-4 cc) will be obtained for assays of eicosanoids, steroid hormones, cytokines, matrix metalloproteinases and for microbial studies; (2) utilize antibiotics with and without potent inhibitors of proinflammatory cytokine production (dexamethasone,IL-10) o prostaglandin production (indomethacin) to ascertain the most effective intervention to down-regulate the cytokine/prostaglandin cascade and associated uterine activity; (3) infuse proinflammatory cytokine IL-1beta into the amniotic cavity through indwelling catheters in the absence of infection. Prior to infusion of IL-1beta in the absence of infection, specific novel proinflammatory cytokine inhibitors (IL-1ra and sTNF-R1 PEG) will be used to identify other potentially useful immunomodulators. Samples of the decidua, fetal membranes, tissues, and brain will be obtained at cesarean section for microbiologic, histopathologic studies, immunohistochemistry for cytokines, localization and quantitation of mRNA for cytokines and PGHS-2. Fetal brain will be examined for increased apoptosis associated with white matter lesions. Leukocytes in amniotic fluid and tracheal aspirates will be assessed by flow cytometry Postpartum, the mother will be treated with appropriate antibiotics to eradicate the GBS from the genital tract and returned to the colony. These studies will clarify the pathophysiology of infection-associated preterm labor and will suggest effective interventional strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL ANALYSIS OF CYCLOOXYGENASE 2 Principal Investigator & Institution: Marnett, Lawrence J.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 08-FEB-2001; Project End 31-JAN-2006 Summary: Cyclooxygenase-2 (COX-2) is a key enzyme of arachidonic acid metabolism and an important contributor to a range of acute and chronic human diseases. COX-2 inhibitors are antiinflammatory, analgesic, and cancer chemopreventive but lack the serious gastrointestinal side effects that plague traditional non-steroidal antiinflammatory drugs (NSAIDs). Our laboratory is interested in the structural basis of catalysis and inhibition of COX-2. We recently reported a fluorescence quenching technique for monitoring enzyme-inhibitor association and dissociation in real time and used it to demonstrate that the COX-2-selectivity of diarylheterocycle inhibitors is due to their very slow dissociation from the enzyme compared to COX-1. We propose to use fluorescence quenching to explore the role of residues in a side pocket of the cyclooxygenase active site and in the constriction that leads to the cyclooxygenase active site in the binding and release of diarylheterocycles from the enzyme. Studies of enzyme-substrate interactions led us to design a novel series of covalent and noncovalent COX-2 inhibitors. Conversion of carboxylic acid-containing NSAIDs into neutral ester or amide derivatives dramatically increases their selectivity for COX-2. We propose to use site-directed mutagenesis and X-ray crystallography to elucidate the molecular basis for interaction of COX-2 with a series of indomethacin amides and esters. Finally, our studies of COX-2 interactions with NSAID esters and amides led us to discover a novel substrate for COX-2 that may provide a new pathway of signal transduction. We propose to investigate the metabolism of 2- arachidonylglycerol by COX-2, the molecular basis for its enzyme specificity, and the ability of its endoperoxide metabolite to be converted into glyceryl eicosanoids. These investigations will provide important new insights into the function and inhibition of COX-2, a key enzyme of lipid signalling and human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC VARIATIONS AFFECTING GP IB-IX/IIB-IIIA AXIS Principal Investigator & Institution: Bray, Paul F.; Professor; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002 Summary: Despite significant progress over the past several decades, disease of the arterial vasculature continues to be the most important cause of morbidity and mortality in this country. Platelet hyperreactivity has been correlated with ischemic events and mortality in patients with vascular disease of the coronary, cerebral and peripheral and peripheral arteries. Platelet membrane glycoproteins are polymorphic and our preliminary studies demonstrate 1) significant associations between ischemic coronary events and polymorphisms on GPIbalpha and integrin beta 3 and 2) combined effects of these polymorphisms on platelet reactivity. However, relatively little information is available suggesting these genetic changes affect receptor function. Because of the central role played by GPIb-IX and alphaIIbbeta3 in the development of ischemic events in the arterial vasculature, the hypothesis driving out studies is that certain isoforms of these receptors induce conformational changes making them hyper- reactive and that these effects are additive or synergistic. The major goal of this proposal is to characterize functional differences among the different isoforms of GPIba and integrin beta 3 and to assess their additive and synergistic effects. In Aim 1 we will generate cell lines that

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express both GPIb-IX and alophaIIbbeta3 and assess the relative effects of the met/thr145 and VNTR polymorphisms on GPIbalpha function and the additive effects of the GPIbalpha and P1/A2 polymorphisms. Using primarily assays employ shear forces, we will test adhesions to appropriate substrates, activation of alphaIIbbeta3, actin cytoskeletal rearrangements, and the relative contribution of the tyrosine kinase, Syk, to signaling by each receptor. GPIb-IX and alphaIIbbeta3 are receptors for thrombin and pro-thrombin, and in Aim 2, the effect of genotype on fibrin generation will be studied by measuring pro-thrombin binding to alphaIIbbeta3, thrombin binding to GPIbalpha, and the conversion of prothrombin to thrombin. We have previously identified P1/A genotype- dependent differences in pp125/FAK and MAP kinase phosphorylation and inhibition by indomethacin, and Aim 3 will extend these studies by assessing beta3, phosphorylation, the role of ras proteins, MAP kinase, phospholipase A2, and arachidonic acid metabolism. These studies would greatly enhance our understanding of genetic effects on platelet physiology, provide key mechanistic information to support or refute clinic genetic association studies, and provide a rationale for our long- term goal of tailoring anti-thrombotic therapy according to a patient's thrombotic risk phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GONADOTROPINS & COX-2 IN OVARIAN CANCER PREVENTION Principal Investigator & Institution: Xu, Xiangxi; Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The gonadotropin stimulation hypothesis is a leading idea in the etiology of ovarian cancer explaining the association of cancer risk with the number of ovulatory cycles. However, gonadotropins have only unremarkable effects on the growth of ovarian surface epithelial cells in culture. Thus, a convincing mechanism for the ovarian carcinogenic activity of gonadotropins is lacking. Recently, we found that pre-neoplastic ovarian surface epithelia that are located immediately adjacent to morphologically neoplastic lesions often lack basement membranes and have proposed that the loss of basement membrane is an early step in ovarian tumorigenicity. Thus, we hypothesize a mechanism for the carcinogenic effect of gonadotropins, that the hormones stimulate the loss of basement membranes similar to pre-ovulatory events. As a result, the frequent placement of the ovarian surface epithelium in such a basement membrane-less, pre-neoplastic stage by repeated gonadotropin stimulation increases the frequency for tumor prone cells to transform Gonadotropins induce Cox-2 in both granulosa and surface epithelial cells to mediate ovulation, and the loss of basement membrane and other ovulatory events can be blocked by inhibition of the Cox enzymes. The W or Wv mice are predisposed to tubular adenoma formation from the ovarian surface epithelium. The cause of ovarian neoplasm is thought to be the elevated serum gonadotropins in these spontaneously mutant mice. Another genetically engineered mutant mouse, the Disabled-2 (Dab2) heterozygous knockout model, is also predisposed to the development of ovarian surface epithelial dysplasia and papillomatosis, the premalignant lesions of ovarian cancer. We speculate that the combination of Wv/Wv and Dab2 () genotypes will augment the predisposition to ovarian neoplasm. We will test if the inhibition of Cox enzymes reduces the gonadotropin stimulated basement membrane loss, and inhibits or reduces the predisposition of the Wv/Wv, Dab2 () mice to develop ovarian tumors. To investigate the mechanisms, we will also examine the effects of gonadotropin stimulation on the expression of Cox-2, collagen IV, laminin, and MMPs in ovarian surface epithelial cells in culture. These studies will help to

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Indomethacin

understand the etiology of ovarian cancer related to gonadotropins, and provide a mechanism(s) for the chemopreventive activity of Cox-2 inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: H+ NEUTRALIZATION AND C1- HOMEOSTASIS IN GASTRIC MUCOSA Principal Investigator & Institution: Soybel, David I.; Associate Professor of Surgery; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JAN-2003 Summary: (Adapted from investigator's abstract) This application represents a continuation of the principal investigator's FIRST Award. The long-term goal of this project is to evaluate, at the cellular level, the mechanisms that protect gastric mucosa from the damaging effects of luminal acid. Until recently, it was accepted that a Cl/HCO3- exchanger, located in the basolateral cell membrane, is responsible for regulation of intracellular Cl- levels (aiCl) and intracellular pH (pHi) in surface cells and oxyntic cells. We recently found evidence to suggest that a basolateral Na-K-Cl cotransport process plays a dominant and previously unsuspected role in preserving intracellular Cl- levels of the surface cells and in regulating HCl secretion by oxyntic cells. These findings have altered the previous model and led to the following hypotheses: 1) a basolateral, HCO3--independent, Na-K-Cl cotransporter is the dominant mechanism for regulating aiCl of oxyntic cells and surface cells in Necturus gastric fundus during stimulation of acid secretion; 2) a complementary, Cl-independent mechanism of basolateral HCO3-extrusion is also present in the oxyntic cell and contributes significantly to the "alkaline tide" generated by high rates of acid secretion; 3) expression of basolateral transporters that are dominant in preserving aiCl and pHi in the oxyntic cells is regulated by the gastric neurohumoral milieu; 4) secretory activity of the oxyntic glands plays a major role in regulating cell pH and ion composition of the neighboring surface epithelial cells during high rates of acid secretion and during exposure to ulcerogenic conditions; and 5) the ammonium (NH4+) ion that is produced by the pathogen H. pylori may gain access to the cell via the Na-KCl cotransporter, leading to disturbances in both aiCl and pHi. Studies proposed in this application will address these hypotheses using intracellular microelectrode and fluorescence techniques for measuring pH and ion composition, and molecular methods for evaluating expression of membrane transporters. The specific aims of this application are organized into four parts. First, we will evaluate the relationship of the basolateral Cl--transporting processes and their implications for regulation of HCO3transport and other protective functions in both surface cells and oxyntic cells in the mucosa of the gastric fundus of Necturus. Second, we will examine, in both amphibian and mammalian models, the effects of secretory agonists such as gastrin, histamine, carbachol in stimulating synthesis and expression of the basolateral HCO3- and Cltransport systems in surface cells and oxyntic cells of gastric mucosa. Third, we will evaluate the effects of ulcerogens such as aspirin or indomethacin on activity and expression of basolateral Cl- transport systems in both surface cells and oxyntic cells. Finally, we will explore the interaction between ammonium (NH4+), which is produced by the bacterium Helicobacter pylori, and cell pH and Cl- homeostasis. Using these techniques, we hope to provide detailed information regarding activity and expression of transport processes that preserve ion composition and pH in gastric mucosal cells during acid secretion or exposure to ulcerogenic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV 1 METALLOPROTEASES

PROTEINS

AND

DRUGS

OF

ABUSE

15

AND

Principal Investigator & Institution: Conant, Katherine E.; Assistant Professor; Clinical Research Center; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: HIV infection continues to rise in drug users, putting them at greater risk of developing dementia. The pathobiology of HIV dementia is only partly understood, however, it is clear that disruption of the blood brain barrier facilitates the entry of peripheral blood monocytes into the brain. Activated and HIV-1 infected monocytes within the central nervous system (CNS) can in turn damage neighboring cells through the release of infectious virus and/or potent neurotoxins. It has recently been shown that drugs of abuse such as cocaine can disrupt the blood brain barrier (BBB), though the associated mechanisms are not well understood. Critical components of this barrier include extracellular matrix proteins such as collagen IV and laminin. Extracellular matrix proteins are regulated by an endogenous family of proteins called matrix metalloproteases (MMPs). These proteases are released not only by activated T cells and monocytes as they migrate through the BBB, but also by resident cells of the brain parenchyma. It has been shown that injection of MMPs into the parenchyma of the brain causes a disruption of the BBB which is followed by leukocytic infiltration of the central nervous system (CNS). Moreover, MMPs produced within the brain parenchyma may have more direct effects on CNS structure and function in that extracellular matrix proteins are known to affect synaptic structure as well as neuronal survival. In the present study, we will therefore address the possibility that both HIV-1 proteins and drugs of abuse will increase MMP production by brain-derived cells. We will also examine the mechanisms by which these substances may affect MMP production, and identify clinically tolerable compounds which may inhibit such production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VIVO IMAGING OF LEUKOCYTE-ENDOTHELIAL DYNAMICS Principal Investigator & Institution: Mathers, William D.; Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The process of leukocyte migration across the vascular endothelial barrier is fundamental to the process of inflammation and the response to infection. We will quantitate the effect of various medications such as topical corticosteroids, oral nonsteroidal anti-inflammatory drugs, and mast cell stabilizers in several of these processes. We have applied intravital microscopy in animal systems to visualize, quantitate and analyze this process. Recent advances in confocal microscopy have allowed a European group to quantitate leukocyte endothelial rolling and sticking in the microvasculature of the human eye. Combining our clinical expertise in confocal microscopy and our experience analyzing leukocyte vascular interactions, we propose to utilize in vivo confocal technology to quantitate leukocyte rolling and arrest in 4 different human vascular beds: the limbus, conjuctiva, episclera, and sclera. With these three specific aims: Aim one, we propose to image rolling and sticking of leukocytes in four different normal ocular vascular beds: the conjunctiva, limbus, episclera, and sclera. Aim two, we will compare leukocyte-endothelial dynamics in specific vascular beds in seven disease states: a) allergic seasonal conjunctivitis, b) Sjogren's syndrome and dry eye, c) blepharitis, d) graft versus host disease (GVHD), e) episcleritis, f) scleritis, and g) anterior uveitis. Aim three, we will determine the effect of medications including topical

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Indomethacin

prednisolone acetate, a mast cell stabilizer (optipranolol), or an oral nonsteroidal antiinflammatory drug (indomethacin) on endothelial-leukocyte dynamics in diseases for which each is frequently prescribed. Our studies will directly clarify the pathogenesis of several troublesome and rarely studied ocular disease processes. These studies will elucidate the mechanism by which medications alter these processes. Most importantly these studies will quantitate a fundamental human biological process in microvascular beds that have not previously been imaged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDOMETHACIN AND P38 REGULATING AP-1 IN HEAT SHOCK Principal Investigator & Institution: Locke, Jacob E.; Radiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term objective of this work is to determine if the constitutive activation of the AP-1 transcriptional complex is one mechanism for how tumor cells gain resistance to the cytotoxicity of hyperthermic radiosensitization. In addition, we will determine if the upstream signaling factor, p38, is a target to both inhibit the AP-1 transcriptional complex and inhibit the resistance to hyperthermic radiosensitization. This mechanistic information is potentially important to improving tumor cell responses to heat-induced radiosensitization, which is currently being evaluated as a therapeutic modality. Preliminary results suggest that: (1) heat shock activates AP-1 DNA-binding activity via a mechanism involving the redox sensitive signaling factor Ref-1 in HeLa and NIH 3T3 cells; (2) OC-14 peroxide resistant cells overexpress c-Fos, c-Jun, and exhibit elevated AP-1 DNA activity when compared to their parent cell line, HA-1; (3) OC-14 cells are resistant to the cytotoxicity from hyperthermic radiosensitization; (4) indomethacin inhibits both the increase in AP-1 DNA-binding activity and the resistance to hyperthermic radiosensitization in OC-14 cells; and (5) a specific chemical that inhibits p38, SB20358 abolishes the effect of indomethacin and restores the increase in AP-1 DNA-binding activity and the resistance to hyperthermic radiosensitization in OC-14 cells. There is considerable evidence that transient activation of specific cytoplasmic signaling and nuclear transcription factors may play a protective role in the tumor cell response to therapeutic modalities. Thus, the proposed work will test the hypothesis that one mechanism for resistance to hyperthermic radiosensitization involves AP-1 transcription complex activation. In addition, it will be determined if p38 is an upstream signaling factor involved in both the activation of AP-1 and resistance to hyperthermic radiosensitization. The specific aims are: 1) determine if two human H202 resistance tumor cell lines are also resistant to hyperthermic radiosensitization and if the AP-1 complex is also constitutively activated, similar to OC-14 cells; 2) determine if AP-1 constitutive activity, using permanent transfected HeLa cell lines that overexpress cFos/c-Jun wild-type and dominant positive proteins, results in a phenotype similar to OC-14 cells; 3) determine if the mechanism of indomethacin-induced inhibition of AP-1 DNA-binding activity is due to inhibition of gene expression, mRNA stabilization, protein degradation, or alteration of the activity of the basic DNA-binding domain of cfos/c-jun, 4) determine if mitogen-activating kinase p38 is a target molecule for indomethacin induced inhibition of AP-1 activity and a target for inhibition of the resistance of OC-14 cells to hyperthermic radiosensitization using either a dominant negative p38 vector or a constitutive dominant positive upstream activator of p38, MKK6b. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INDOMETHACIN FOR ADJUVANT TOCOLYSIS Principal Investigator & Institution: Macones, George A.; Associate Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-NOV-2004 Summary: (Adapted from Investigator's Abstract) Preterm labor is a common and serious complication in pregnancy in the United States, occurring in approximately 400,000 pregnancies per year. Magnesium sulfate is currently the most commonly prescribed agent for tocolysis in the United States. However, up to 35% of patients treated with magnesium sulfate fail therapy. In this setting, the most common strategy in the United States is to add indomethacin as adjuvant therapy. Unfortunately, there are no data to support that this strategy will improve outcome. In addition, recent data suggested that neonatal outcome may be worsened when indomethacin is used in this setting. The goal of the project is to use a randomized clinical trial to test the hypothesis that indomethacin, when used for adjuvant tocolysis in preterm labor (i.e., in those who are failing to respond to conventional first-line therapy) can decrease the rate of major neonatal complications and death. The proposed research project will use a doubleblind, parallel, randomized, controlled clinical trial design to compare the efficacy of indomethacin to placebo for adjuvant tocolysis in pregnancies less than 30 weeks gestation. Patients will be recruited for this study from the Labor and Delivery wards of the Hospital of the University of Pennsylvania, Pennsylvania Hospital, Thomas Jefferson University Hospital, and Christiana Care Health Services. Patients who fail first-line therapy with magnesium sulfate will be evaluated for possible enrollment into this randomized clinical trial. Those who give informed consent will be enrolled into the study. This study calls for the enrollment of 205 patients in both arms. Patients will be randomized to receive either indomethacin rectal suppositories (50 mg every 6 hours) or identical-appearing placebo suppositories for a maximum of 48 hours. After completion of treatment with either placebo or indomethacin, patient care will be largely at the discretion of the attending physicians. Many prior studies of tocolysis have used variable periods of delay in delivery as the primary outcome measure. The investigators believe that this is not the appropriate primary endpoint, since the ultimate goal of tocolysis is to improve neonatal outcome. Thus, although delivery delay will be analyzed as a secondary endpoint, the primary outcome (on which the sample size is based) will be based on neonatal morbidity. Specifically, the primary outcome measure for this study will be a dichotomous composite neonatal morbidity/mortality outcome measure. A neonate will be classified as having an adverse neonatal outcome if he/she suffers from any major morbid condition (defined as necrotizing enterocolitis, death, intraventricular hemorrhage, respiratory distress syndrome, or chronic lung disease). Secondary outcomes for analysis will include: (1) time from randomization until delivery, (2) mean gestational age at delivery, (3) major maternal side effects, (4) need for re-admission for tocolysis, (5) infant birth weight, and others. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF AIRWAY INFLAMMATION IN ASPIRIN INTOLERANT ASTHMA Principal Investigator & Institution: Langmack, Esther; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 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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Indomethacin

Project Title: METABOLIC DISPOSITION OF CYCLOPENTENONE EICOSANOIDS Principal Investigator & Institution: Roberts, L Jackson.; Assistant Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: (provided by applicant) Prostaglandin D2 (PGD2) is an unstable molecule that can undergo dehydration to form PGJ derivatives, delta 12-PGJ2 and 15-deoxydelta12,14-PGJ2. There has been considerable interest in these PGJ2 compounds owing to the fact that they have been shown to modulate tumor cell proliferation, inhibit Nf kappaB activation, and exert anti-inflammatory activity in vitro. More recently there has been an upsurge in the interest in these compounds because they have been shown capable of activating the nuclear receptor, PPAR gamma. However, there is has been no convincing evidence to support the notion that these cyclopentenone derivatives of PGD2 are actually formed in relevant quantities in vivo. However, we recently convincingly demonstrated the formation of PGA2/J2-1ike compounds esterified in tissue phospholipids in rats as products of the isoprostane pathway in vivo but it remains to be established whether PGD2 produced by the cyclooxygenase also undergoes dehydration in vivo. We had previously demonstrated that alpha l2-PGJ2 rapidly conjugates to glutathione and cysteine in vitro. We also demonstrated that alpha 12-PGJ2 undergoes extensive conjugation with glutathione in CHO cells after which the C-11 carbonyl is reduced to an alcohol and further metabolized to cysteinylglycinyl and cysteinyl derivatives. Moreover, following intravenous administration of radiolabelled Alpha 12-PGJ2 to rats we found that all of the radioactivity excreted in to the bile and urine was in the form of a polar conjugate(s). This suggests that the detection of the formation of PGJ2 derivatives in vivo can only be accomplished by analysis of their conjugates. Therefore, we propose to determine the metabolic disposition of Alpha 12PGJ2 and 15-deoxy-Alpha 12,14-PGJ2 in a non-human primate and develop mass spectrometric assays for the major species excreted into the urine. We will then assess whether these metabolites can be detected in normal human urine and whether levels increase in patients with systemic mastocytosis which is associated with a marked overproduction of PGD2 and in normal volunteers following administration of niacin, which induces a release of prodigious quantities of PGD2. We will also determine the relative contribution of the cyclooxygenase and isoprostane pathways to the levels of these metabolites in human urine by treatment of subjects with inhibitors of the cyclooxygenase enzyme. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROGLIAL SIGNALING MECHANISMS IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Landreth, Gary E.; Professor; Neurology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 31-JAN-2005 Summary: (adapted from applicant's abstract) Alzheimer's Disease (AD) is characterized by the extracellular deposition of compacted fibrillar forms of B-amyloid (AB) protein within the brain. These senile plaques are the focus of a complex cellular reaction, the most prominent which is the presence of abundant reactive microglial cells that are found adjacent to and invest in the senile plaques. Microglia are derived from a monocytic lineage and are the sole immune cell in the brain. Microglial activation is accompanied by enhanced expression of numerous cell surface proteins an elaboration of a complex array of proinflammatory and acute phase products. There is compelling

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evidence that there is a significant inflammatory component in Alzheimer's disease as evidenced by a diverse range of clinical studies which have shown that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) substantially reduces the incidence of AD-related dementia delays disease progression. The central hypothesis guiding these studies is that microglia can detect and respond to fibrillar forms of amyloid by activation of intracellular signaling pathways which subserve the "activation" of the cells and the consequent secretion of proinflammatory products. The Specific Aims of this proposal are: 1. The characterization of membrane proteins that interact with AB fibrils and serve as primary signal transducing elements linked to intracellular signaling pathways. We demonstrate that the B-class scavenger receptor, CD36, and an integrin mediate the adhesion of monocytes to AB fibrils and activation of tyrosine kinase based signaling cascades. We propose to identify the relevant integrin and ascertain how these cell surface molecules are linked to intracellular signal transduction complexes. 2. Identification of the signal transduction pathways activated in response to AB which subserve the production of proinflammatory products and the acquisition of an activated phenotype by the microglia. Specifically, we will investigate signaling pathways that mediate the activation of the transcription factors NFkB and the peroxisome proliferation activated receptor, PPARy. We will also investigate ABinducted expression of cyclooxygenase-2. 3. We propose to employ an animal model of Alzheimer's disease to the effects of anti-inflammatory drugs on microglial activation. Transgenic mice expressing mutant forms of both the amyloid precursor gene and the presenelin 1 gene develop amyloid plaques and exhibit dramatic activation of plaqueassociated microglia. We will test the efficacy of the classical NSAID, indomethacin, as well a PPARy agonists and a COX-2 specific inhibitor in blocking the acquisition of a reactive phenotype by microglial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Coleman, Amber C.; Chemistry and Biochemistry; Florida Atlantic University Boca Raton, Fl 33431 Timing: Fiscal Year 2002; Project Start 24-AUG-2002; Project End 02-MAY-2003 Summary: The pseudopterosins and seco-pseudopterosins are diterpene glycosides isolated from the marine soft coral, Pseudopterogorgia elisabethae. These compounds exhibit anti-inflammatory and analgesic activity greater than the industry standard, indomethacin. Our objective is to develop a production method of these potent compounds and biosynthetically related anti-inflammatory metabolites by completing biosynthetic studies, enzymology and synthetic work. We plan to elucidate the biosynthetic pathway in order to gain detailed knowledge of the biosynthesis and enzymology of the system, and utilize the information in the development of the production method. In addition, purification of the diterpene cyclase will supply sequence data needed to facilitate cloning of the enzyme into a vector. Synthetic aromatization and oxidation of the cyclized enzymatic product will be studied in order to produce the promising anti-inflammatory compounds in significant quantities. Since the only present supply of these compounds is from extraction of harvested coral, this production method could provide these compounds for clinical development or for a commercial market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROPATHIC PAIN FROM AN EXPERIMENTAL NEURITIS Principal Investigator & Institution: Bennett, Gary J.; Professor; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 03-JUL-1998; Project End 30-JUN-2004 Summary: An experimental inflammation of the rat's sciatic nerve (a neuritis) has been produced by applying Complete Freunds Adjuvant to the surface of the nerve at the mid-thigh level. The neuritis produces heat- and mechano-hyperalgesia and cold- and mechano-allodynia in the ipsilateral hind paw that last for up to 5-6 days. At the time of peak symptom severity, there is an endoneurial immune cell infiltrate and evidence for plasma extravasation at the site of treatment, but little or no structural damage to axons or glia. The absence of degeneration and regeneration in the nerve, and the brief duration of the syndrome, are uniquely different than all present models of neuropathic pain. The mechanisms producing neuropathic pain in the territory of the inflamed nerve are likely to be distinctly different than those producing pain after cutaneous injury because the latter involves changes in receptor terminal transduction and impulse generation properties that are not present at "mid-axon" level. Our results suggest two novel concepts: (1) a focal, strictly inflammatory process in a nerve may give rise to neuropathic pain sensations in a distant region, and (2) such pain may be due to a neuroimmune interaction that generates ectopic discharge in uninjured nociceptor axons. The objectives of this proposal are to discover the causative factors involved in the genesis of the pain. Histological and immunocytochemical techniques will be used to determine the spatial and temporal extent of the inflammation, to identify the immune cell types that infiltrate the nerve, to determine whether pro-inflammatory cytokines and NGF are present, and to confirm the presence of plasma extravasation. To test whether a neuroimmune factor is involved, inhibitors of immune function will be given to see if they prevent the neuropathic pain. Electrophysiological recordings from identified sensory axons will determine if abnormal discharge arises at the site of inflammation and if there is peripheral sensitization due to an antidromically-conducted ectopic discharge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROSTEROIDS: PHYSIOLOGICAL RELEVANCE Principal Investigator & Institution: Guidotti, Alessandro; Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 30-JUN-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NO AND THE MAGNOCELLULAR NEUROENDOCRINE SYSTEM Principal Investigator & Institution: Kadekaro-Kutyna, Massako; Professor; Surgery; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) The investigators have shown previously that nitric oxide (NO), a lipophilic gas synthesized by NO synthase (NOS) from L-arginine, has important functions in neuroendocrine and behavioral osmoregulation, as well as blood pressure control. The experiments proposed in this application will clarify the site and mechanisms by which NO modulates the magnocellular neuroendocrine system. Since NO is synthesized in magnocellular

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neurons and cells in the supraoptic nuclei (SON) project almost exclusively to the posterior lobe of the pituitary gland to regulate neuroendocrine responses to fluid and electrolyte imbalances our studies will focus on the SON. The studies are designed to test two hypotheses: 1) NO synthesized locally in the SON during osmotic stimulation activates guanylyl cyclase to increase 3',5' cyclic guanosine monophosphate (cGMP) which results in 2) inhibition of angiotensin II and prostaglandin release in the SON to attenuate peripheral secretion of oxytocin. The specific aims are to determine: 1a) whether the activities of NOS (i.e. citrulline) and guanylyl cyclase (i.e. cGMP) increase in microdialysates of the SON during osmotic stimulation; 1b) whether inhibiting the production of NO with L-Name retrodialyzed in both SON prevents the increase of cGMP in microdialysates associated with increasing plasma levels of oxytocin during osmotic stimulation; 1c) whether retrodialyzing both SON with 1H-[1,2,4) oxodiazolo [4,3-a)quinoxalin-1-one (ODQ), a specific inhibitor of soluble guanylyl cyclase, decreases intranuclear production of cGMP and reproduces the effects of L-Name on plasma secretion of oxytocin during osmotic stimulation. 2a) whether ANG II and prostaglandin levels increase locally in the SON following retrodialysis with L-NAME during osmotic stimulation; 2b1) whether this neuroendocrine response to L-NAME can be prevented by losartan, an ANG II AT1 subtype receptor antagonist, or 2b2) indomethacin, an inhibitor of cyclooxygenase, the enzyme that converts arachidonic acid to prostaglandins. This research is important because it will further our understanding of the neurobiology of body fluid regulation by NO. Since NO is required for plasticity of neural systems involved in learning and memory, as well as participates in neurotoxicity, clarifying the mechanisms of action of this novel neurotransmitter may lead to new drug therapies selective for treatment of pathological disorders affecting water balance with minimal effect on other physiological responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSIOLOGICAL ADAPTATION TO STRAIN IN AIRWAY EPITHELIUM Principal Investigator & Institution: Waters, Christopher M.; Associate Professor; Physiology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 07-SEP-1999; Project End 31-AUG-2004 Summary: The airway epithelium represents the first line of defense for the lungs against inhaled-pollutants and infectious agents. Injury to the airway epithelium occurs during mechanical ventilation and in inflammatory diseases such as asthma. Movement of air into and out of the lungs during respiration causes wide variations in the distension of airways, and the epithelial cells lining the airways are thus exposed to both circumferential wall strain depending upon changes in airway diameter and longitudinal elongation or compression depending upon the expansion of the lung volume. Although there has been much interest in the function of epithelium in response to injury and in the pathogenesis of asthma and other chronic obstructive diseases, there has not been an investigation of the role of mechanical strain on the function of airway epithelium. The central hypothesis of this proposal is that physiological levels of mechanical strain regulate the rate of wound closure and the synthesis of eicosanoids in airway epithelial cells by mechanisms involving reactive oxygen species. This hypothesis will be investigated by stretching both primary cultures of cat tracheal epithelial cells and human bronchial epithelial cells as well as lines of human bronchial epithelial cells grown on elastic membranes using a novel biaxial strain device. Preliminary results demonstrate that both cyclic mechanical elongation and compression delay wound closure by inhibiting cell spreading and migration.

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Furthermore, indomethacin inhibits and prostaglandin E2 (PGE2) enhances wound closure. Cyclic strain inhibits synthesis of PGE2, and other prostanoids by inactivating the enzyme cyclooxygenase (COX). Preliminary evidence also suggests that COX inactivation is oxidant-mediated. In Specific Aim 1, the mechanisms by which cyclic stretch and compression inhibit wound closure in epithelial monolayers will be determined. Measurements of wound width, cell area, and internuclear distances will indicate cell spreading and migration at the wound edge. In Specific Aim 2, the mechanisms by which cyclic strain regulates the metabolism of arachidonic acid to prostanoids will be determined. Western blots of COX-l and COX-2 protein expression and Northern blots of mRNA levels will be used to determine the adaptation response to cyclic strain. In Specific Aim 3, the role of epithelial oxidant/antioxidant balance in the stretch-induced regulation of wound closure and COX inhibition will be examined. Investigation of the mechanisms underlying epithelial repair and injury during cyclic strain may lead to better strategies for the management of patients during mechanical ventilation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PPAR GAMMA AGONISTS FOR THE PREVENTION OF COLON CANCER Principal Investigator & Institution: Wargovich, Michael J.; Professor; Pathology and Microbiology; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 05-JAN-2001; Project End 31-DEC-2003 Summary: Epidemiological studies strongly associate non-steroidal anti- inflammatory drug (NSAID) use with reduced risk for colon cancer. NSAIDS prevent colon cancer. However, alternative explanations may exist. Certain NSAIDS are ligands for peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily of transcription factors. The overall investigating agonists of PPAR gamma as possible chemopreventives for colon cancer. Colon cancer is the second cancer. The hypothesis to be tested is that agonists of PPAR gamma, a form of PPAR highly expressed in the colon epithelium and colon tumors, will be chemopreventive for he colon. I propose two aims to test the hypothesis, protein expression in rat colon epithelium. Effects on normal and colon carcinogen-treated rodent colon will be explored. We will test troglitazone, pioglitazone, rosiglitazone, BRL 49653 and the antiinflammatory NSAIDs, indomethacin and ibuprofen. Results from these studies will provide a direct link between the reportedly elevated expression levels of PPAR gamma in the colon and compounds that activate it. In Aim 2, we will determine in the rat colon using inhibition of aberrant crypt foci (ACF) as an intermediate endpoint. These studies are aimed at determining whether PPAR gamma agonists are inhibitors of tumorigenesis in vivo. Secondary studies will assess the effects of these compounds on colonic cell proliferation and apoptotic rates. These studies will define PPAR gamma as a possible target for chemopreventive drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DISABILITIES

PREDOCTORAL

FELLOWSHIPS

FOR

STUDENTS

WITH

Principal Investigator & Institution: Alberding, Jonathan P.; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-JUL-2002

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Summary: (provided by applicant): Study of Filtration Under Pulsatile Pressure in Large Arteries. Measuring filtration in large arteries undergoing pulsatile pressure is rarely attempted due to the difficulty of distinguishing effects of arterial distension from those of true filtration. Accurate measurements of filtration are necessary to evaluate convective lipoprotein deposition in large arteries. My preliminary results show that pulsatile pressure induces a transient increase in apparent filtration. However, this could be mediated by an increase in arterial distension. Optical Coherence Tomography now permits accurate measurements of vessel distension so that true filtration can be determined. Using this technique the effect of pulsatile pressure on arterial transport and mechanical properties will be evaluated. The aims are as follows: 1) To determine whether pulsatile pressure increases arterial hydraulic conductance or residual distension. 2) Observe whether the apparent increase in filtration occurs after a change in pulsatile pressure amplitude and/or frequency as well as at the onset of pulsatile pressure. 3) Use paired carotid arteries (one de-endothelialized) to measure the effects the endothelium has upon the response. 4) Observe the effects of pulsatile pressure on gaps in endothelial junctions (provided the observed filtration is found to be endothelial-mediated), using Silver Nitrate staining. 5) If apparent filtration is due to changes in arterial distension, rather than changes in hydraulic conductance: A) Use an eNOS inhibitor to see if distention is Nitric oxide dependent. B) Or use indomethacin and/or ibuprofen to see if the distension is dependent on release of vasodilators PGI2/PGE2 from smooth muscle cells and/or endothelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTANOIDS AND LIVER MICROCIRCULATION IN STRESSES Principal Investigator & Institution: Zhang, Jian X.; Biology; University of North Carolina Charlotte Office of Research Services Charlotte, Nc 282230001 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Endotoxemia is a common but severe complication of cirrhosis frequently causing liver injury and even organ failure. The mechanism underlying the increased susceptibility of the cirrhotic liver to endotoxemia in the sequential stresses, however, is not completely understood. Studies have shown a hepatic upregulation of constrictor endothelin (ET) and a decreased release of vasodilator nitric oxide (NO) in the cirrhotic liver. Our preliminary studies have shown that in cirrhosis, constrictor prostanoids are released in response to ET, and the action of the prostanoids is modulated by NO. We also showed that endotoxemia as a secondary stress caused an additional upregulation in already increased ET gene expression in the cirrhotic rat liver, but endotoxin-induced expression of inducible nitric oxide synthase was blunted by the preexisting cirrhosis. We therefore hypothesize that liver cirrhosis as a pre-existing condition primes the hepatic microcirculation for predisposition to an imbalance between constrictor and dilator influences by sensitizing the ET/constrictor prostanoids pathway and decreasing production of NO. We further hypothesize that endotoxemia as a secondary stress further activates the pathway leading to dysregulation of the hepatic microcirculation and ultimately hepatocellular injury. To test these hypotheses, three specific aims are proposed: 1) determine whether cirrhosis as a pre-existing condition primes the hepatic microcirculation for predisposition of an imbalance between constrictor and dilator influences by sensitizing the ET-mediated release of vasoconstrictor prostanoids; 2) determine whether endotoxemia as a secondary stress enhances the pressor response mediated by the release of vasoconstrictor prostanoids in response to ET; 3) determine whether an overwhelming increase in ET accompanied by the sensitization of ET-induced release of prostanoids

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and an attenuated expression in iNOS following the sequential stresses result in an imbalanced regulation of vasoconstriction and vasodilation and dysregulation of the hepatic microcirculation. This proposal not only will allow us to evaluate the role of constrictor prostanoids in regulation of hepatic microcirculation in cirrhosis and endotoxin-induced sequential stresses, but also will provide invaluable information on therapeutic strategies to prevent hepatic microcirculatory failure under the double stressed conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTOGLANDINS AND UVB CARCINOGENESIS Principal Investigator & Institution: Oberyszyn, Tatiana M.; Assistant Professor; Pathology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2004 Summary: The skin has historically been considered to function as a barrier against chemical or physical insults from the external environment. In addition to these barrier functions, the skin is now recognized to be an organ with important immunological and biochemical functions that can impact the health of the entire organism. Ultraviolet B radiation (UVB, 290-320nm) is responsible for the majority of cutaneous damage following both acute and long term exposure and is believed to be the single most important etiologic agent in human skin cancer. UVB carcinogenesis has recently been associated with an inflammatory response that includes the production and release of prostaglandins, which may be critical to the observed damaging effects of UVB on skin, which include the formation of oxidative DNA adducts. The underlying Hypothesis for the proposed studies is that there is a link between selective induction of one of the isoforms of the gene responsible for prostaglandin production, i.e. cyclooxygenase-2 (COX-2), and the resulting formation of oxidative DNA damage within the cutaneous microenvironment which ultimately results in the epigenetic and genetic alterations observed during UVB induced mutagenesis and carcinogenesis. Studies in the first specific aim will take advantage of the development of knock-out mice that do not contain either the constitutive isoform of the COG gene, COX-1 or mice which are COX2 null. These studies will determine the critical nature of the presence of prostaglandins derived from these genes on the formation of DNA adducts, the induction of focal p53 clustering within the hyperplastic skin and to the kinetics of development and growth of UVB- induced papillomas and carcinomas. Studies in specific aim 2 will examine the ability of NSAIDS, specific inhibitors of the cyclooxygenase isoforms including, NS-398 and indomethacin, to prevent UV induced tumor growth. These studies offer a unique opportunity to gain insight into the role that COX-1 and COX-2 derived prostaglandins play in UV induced squamous cell carcinoma development and provide a potentially important pharmacological approach to abrogate or inhibit the deleterious effects of UVB exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RANDOMIZED INDOMETHACIN GMH/IVH PREVENTION TRIAL Principal Investigator & Institution: Ment, Laura R.; Professor; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-SEP-1989; Project End 31-MAR-2005 Summary: Intraventricular hemorrhage (IVH), or hemorrhage into the germinal matrix tissues of the developing brain, remains a major problem of preterm neonates. We enrolled 505 neonates of 600 - 1250 g birth weight in a prospective, randomized,

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placebo- controlled multicenter trial to test the hypothesis that indomethacin would lower the incidence of IVH. This study demonstrated that indomethacin both lowered the incidence and decreased the severity of IVH in preterm infants with no evidence for hemorrhage at 6 - 11 hours (p = 0.03, trend test). Infants randomized to indomethacin had less parenchymal hemorrhage (p = 0.01), less cerebral ventriculomegaly at term (p = 0.04), and improved survival (p = 0.08) compared to placebo infants. At 54 months corrected age (C.A.) categorical analysis demonstrated a modest benefit on both the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) full scale IQ (p= 0.035) and the Peabody Picture Vocabulary - Revised (PPVT-R, p =0.02). At 72 months C.A., indomethacin children were found to perform significantly better on the WPPSI-R verbal IQ (p = 0.04), the PPVT-R (p = 0.009), and the Vineland Communication Score (p = 0.009) when compared to placebo children; the Child Behavior Check List showed they had better social skills. We hypothesize that at 96 and 144 months C.A. children randomized to indomethacin will score significantly better on measures of cognitive function and achievement than placebo children. These are ages when and the educational demands are great. In addition, based on ultrasound data demonstrating less ventriculomegaly in indomethacin children, we hypothesize that indomethacin subjects will have significantly less cerebral volumetric abnormalities than placebo subjects when the entire cohort is assessed by volume magnetic resonance imaging. Because our indomethacin subjects appear to have significantly better verbal skills than placebo children, we will perform a verbal activation task using functional magnetic resonance imaging to test the hypothesis that indomethacin children will show significantly better patterns of fMRI activation than placebo children. Study subjects will undergo structured, systematic assessments for neuropsychiatric disorders and adaptive capacities in the social domain to test the hypothesis that indomethacin children will have less neuropsychiatric disorders, anxiety symptoms and socialization difficulties than placebo subjects. Finally, multivariate statistical analyses will be performed to determine the independent and important predictors of cognitive outcome and function at 8 and 12 years C.A. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CEREBRAL BLOOD FLOW Principal Investigator & Institution: Busija, David W.; Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-JAN-1991; Project End 30-JUN-2004 Summary: Prostanoids (prostaglandins and thromboxane), cyclooxygenase (COX)derived products of arachidonic acid, are important mediators of cerebrovascular responses in neonatal animals. However, little is known about the in vivo regulation of COX isoforms in cerebral tissues and blood vessels. This proposal is based upon a number of exciting observations by our laboratory. First, cerebral vascular and parenchymal levels of COX-2 (supposed inducible form) but not COX-1 (supposed constitutive form) increase rapidly (2-8 hours) during the reperfusion period after 10 minutes of total ischemia (ischemia/reperfusion; I/R) in piglets. Second, oxygen radicals and prostanoids are produced by I/R prior to induction of COX-2. Third, indomethacin pretreatment suppresses increases in mRNA and protein levels of COX-2 after I/R. Fourth, inhibition of the nuclear transcription factor kappa B (NF-kappaB) or exogenous nitric oxide (NO) inhibits synthesis of COX-2 in cultured astroglia. And fifth, prostanoid- and NO-dependent dilator responses are suppressed following ischemia. Specific hypotheses to be tested: a) Oxygen radicals or prostanoids promote increased synthesis of COX-2; b) Oxygen radical effects on COX-2 synthesis are via activation of

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NF-kappaB; c) Increased COX-2 levels will alter responsiveness of the cerebral circulation; d) NO restrains increases in COX-2 levels after I/R; and f) Substrate availability for NOS and COX will affect COX-2 expression after I/R. To test these hypotheses, two specific aims will be addressed in anesthetized piglets: 1) CHARACTERIZATION OF EFFECTS OF ISCHEMIA/REPERFUSION ON COX LEVELS IN CEREBRAL BLOOD VESSELS AND TISSUES. AND 2) DETERMINATION OF THE MECHANISMS INVOLVED IN REGULATION OF COX LEVELS IN CEREBRAL BLOOD VESSELS AND TISSUES. These studies will expand our understanding of control mechanisms and will provide information to facilitate development of approaches to alleviate vascular and neuronal impairments associated with ischemic-like events in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF THE DUCTUS ARTERIOSUS Principal Investigator & Institution: Clyman, Ronald I.; Cardiovascular Research Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-AUG-2003 Summary: In the premature infant, the doctus arteriosus frequently remains open for many days or weeks after delivery. As many as 70% of newborns delivered prior to 28 weeks gestation will require some form of therapy to close their patient doctus. If left unclosed, a persistent patent doctus arteriosus is associated with significant morbidity: bronchopulmonary dysplasia (with its prolonged need for mechanical ventilation) and necrotizing enterocolitis. Numerous studies have shown that early closure of the doctus arteriosus decreases the severity of bronchopulmonary dysplasia and decreases the incidence of necrotizing enterocolitis. Although inhibitors of prostaglandin synthesis, like indomethacin, induce doctus closure in 85% of preterm infants in whom they are used, doctus reopening occurs in 20-30% of treated infants. Recent studies demonstrate that the postnatal development of doctus wall hypoxia is an essential step in the anatomic remodeling (luminal endothelial proliferation, migration, and smooth muscle cell death) that leads to permanent closure. The studies proposed in this application will examine the mechanisms involved in early, spontaneous doctus closure in the full-term newborn and those involved in the delayed closure of the premature newborn. They will also examine the mechanisms involved in the high rate of doctus reopening after indomethacin-induced closure. They will use the premature baboon model of persistent patent doctus arteriosus, which is the only model that mimics the long-term events surrounding doctus patency in the preterm human. They will examine the hypothesis that vasoactive factors that alter doctus tone (e.g., prostaglandins, nitric oxide) also interact with an deregulate the growth factors and death factors involved in anatomic remodeling. They will examine mechanisms to increase doctus wall hypoxia in the preterm newborn. They will use immunohistochemical, Western, and Northern techniques to study changes in mRNA and protein expression; they will use assays of cell migration, proliferation, and cell death in isolated vessels, endothelial and smooth muscle cells in culture. They will characterize changes in receptor populations and test their findings in vivo. These studies should increase our understanding of what initiates and sustains the process of ductus closure after birth and why it does not occur in the preterm infant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTIVE ATHEROSCLEROSIS

INHIBITION

OF

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CYCLOOXYGENASE-2

IN

Principal Investigator & Institution: Catella-Lawson, Francesca; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRESS-INDUCED SICKNESS BEHAVIOR DURING SEPARATION Principal Investigator & Institution: Hennessy, Michael B.; Professor; Psychology; Wright State University Colonel Glenn Hwy Dayton, Oh 45435 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): In some species of primates as well as guinea pigs, infants exhibit a 2-stage, active/passive, response during maternal separation. This second stage (termed despair in primates) of separation from the maternal attachment figure has provided a long-standing animal model for the study of depressive illness. The proposed experiments will test in guinea pig pups the hypotheses that: (1) passive behaviors (crouched stance, eye-closing, and extensive piloerection together with low levels of vocalizing and locomotor activity) observed during prolonged isolation represent what have come to be known as "stress-induced sickness behaviors" (i.e., components of the inflammatory response that can be elicited by stressors as well as immunologic stimuli); and, (2) that the stress-responsive peptide CRF can stimulate inflammatory reactions to produce the passive behavioral responses. Specific Aim 1 will evaluate the first hypothesis by attempting to reverse the passive behavioral responses and increased core temperature observed in isolated guinea pig pups with: (1) infusion into the cerebral venticles of alpha-MSH, an anti-inflammatory peptide; and, (2) systemic administration of indomethacin, an inhibitor of prostaglandin synthesis. Specific Aim 2 will evaluate the second hypothesis by using the same two techniques to attempt to reverse passive behavioral responses produced by injection of CRF. Positive results in the proposed studies would provide an alternative perspective from which to view elements of the classic maternal separation response and would support recent conceptualizations of aspects of depressive symptomatology as behavioral components of the inflammatory response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND MECHANISM OF PROSTAGLANDIN H2 SYNTHASE Principal Investigator & Institution: Loll, Patrick J.; Biochemistry; Mcp Hahnemann University Broad & Vine Sts Philadelphia, Pa 19102 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: (adapted from applicant's abstract) The goal of this project is to develop a structural understanding of how prostaglandin H2synthase (PGHS) functions focusing on both the enzyme's recognition of inhibitors and fatty acid substrates and on the relationship between the enzyme's two distinct activities. PGHS catalyzes the conversion of arachidonic acid to prostaglandin H2 and this process is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, naproxen, and indomethacin. The specific aims of the project are: (1) exploration of active site plasticity: structures of PGHS complexed with conformationally constrained

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indomethacin analogs will be determined to investigate the ability of the active site to adopt alternate conformations in recognizing various NSAIDs, and to better understand the possible mechanism by which the cyclooxygenase and peroxidase active sites communicate with each other. (2) Analysis of fatty acid binding and cyclooxygenase catalysis. The nature of the Michaelis complex of arachidonic acid or related fatty acids bound to PGHS will be determined using crystals soaked in substrate solutions under anaerobic conditions. The structural data will be used to elucidate the spatial relationship of the substrate with the radical tryosine 385 in addition to any conformational constraints imposed by the enzyme on the substrate. The purpose of this specific aim is to examine the structures of fatty acids substrates and inhibitors bound to PGHS to test whether tyr-385 is situated appropriately to act as a hydrogen atom abstractor. Specific Aim (3) Examination of the relationship between the peroxidase and cyclooxygenase catalytic activities: structures will be determined of peroxidase deficient forms of PGHS (using chemical modification techniques and/or reconstitution with non-iron metalloporphyrins. Comparison of these structures with that of the peroxidase competent form of the enzyme will contribute to the understanding of the peroxidase mechanism by revealing features of the active site necessary for substrate binding/catalysis. Finally, structures of different cyclooxygenase or peroxidase deficient forms of the enzyme will be determined to help clarify the relationship between the two activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRIAL OF INDOMETHACIN PROPHYLAXIS IN PREMATURE INFANTS Principal Investigator & Institution: Papile, Lu-Ann; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 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: VASCULAR REMODELING: THE DUCTUS ARTERIOSUS MODEL Principal Investigator & Institution: Koller, Beverly H.; Associate Professor; Genetics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: (the applicant's description verbatim): Pharmacological and clinical evidence has implicated prostanoids, arachidonic acid (AA) metabolites produced by cyclooxygenases 1 and 2 (COX-1 and COX-2), in the physiology of the blood vessel. In this proposal, we focus on the ductus arteriosus (DA) as a model for studying the role of prostanoids in vascular remodeling. The DA is an arterial connection in the fetus that directs blood away from the pulmonary circulation and towards the placenta where oxygenation occurs. Permanent closure of the DA depends on a series of structural changes that are independent of the reversible muscular contraction that initially reduces blood flow through this shunt after birth. It has been hypothesized that the DA has an intrinsic tone that is opposed by the dilatory effects of prostanoids such as PGE2 and that a postnatal decrease in levels of circulating prostanoids provides the signal that triggers DA closure. This idea was recently challenged by our observation of mice deficient in the EP4 receptor for PGE2. Contrary to our expectations, we found that the DA in EP4-/- mice remained patent throughout gestation but failed to close after birth,

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leading to perinatal death. To reconcile the results of previous pharmacological studies with those obtained through our genetic approach, we proposed a model in which EP4 expressed by the DA acts as a sensor that triggers closure of the DA in response to a perinatal drop in circulating levels of PGE2. We propose here to use a combined genetic, molecular, and pharmacological approach to develop a comprehensive molecular model for the mechanism by which the PGE2/EP4 pathway contributes to the events leading to vascular remodeling of the DA at birth. In addition, we propose to use a population of mice in which DA closure occurs in the absence of the EP4 receptor to identify other pathways that contribute to vascular remodeling of the DA. We believe that understanding these mechanisms and pathways will improve our general understanding of the way in which blood vessels are remodeled in specific disease states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASOACTIVE DRUGS AND NEONATAL CEREBROVASCULAR REACTIVITY Principal Investigator & Institution: Angeles, Danilyn M.; None; Loma Linda University Loma Linda, Ca 92350 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The candidate's broad experience with the care of sick neonates will be combined with her knowledge of basic science strategies to examine the effects of vasoactive pharmaceuticals such as indomethacin, dopamine and dobutamine on neonatal cerebrovascular reactivity. Although these drugs have wellestablished immediate cardiovascular effects, the more subtle and long lasting effects remain unstudied and unknown. This is particularly true for the cerebral circulation which when compared to the systemic circulation often exhibits unique patterns of responsiveness to many drugs. Most importantly, the long-term cerebrovascular effect of prolonged exposure to these medications during a time when the brain's perivascular innervation and receptor mechanisms are still maturing remains unknown. Utilizing tissues made available through human organ and tissue donation, the present proposal explores the specific hypothesis that exposure of immature cerebral arteries to commonly administered vasoactive pharmaceuticals during the neonatal period alters acute and long-term cerebrovascular reactivity. Because serotonin is a potent vasoconstrictor of cerebral arteries and produces contractions that are at least 100 times stronger than those produced by norepinephrine, the proposed studies will focus on how these pharmaceutical agents alter serotonin-induced tone. Our hypothesis has four corollaries each of which proposes a mechanism whereby exposure to these drugs may be influencing serotonin-induced contractile tone by altering: 1) artery morphology and composition, 2) endothelial function, 3) serotonin dose-response coupling, and 4) serotonin and inositol triphosphate affinity and receptor densities. Upon completion of these studies, the candidate's goal is to establish a translational research center whose main purpose is to examine clinical processes that may influence a neonate's long-term cerebrovascular and neurological function. More specifically, the candidate, in collaboration with nurses, neonatologists, pediatric neurologists and vascular physiologists is initiating a systematic exploration of variables that increase risk for cerebrovascular rupture and hemorrhage. To achieve this goal, the candidate plans to pursue a line of study that will lead to a thorough understanding of variables affecting cerebral blood flow and cerebrovascular smooth muscle function. Resources needed to complete this goal are all available in the candidate's institution. With the institution's and sponsor's commitment to the research career development of the candidate, the

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candidate is optimistic that results from her current and future investigations will lead to modification in therapies and an improvement in the quality of care given to critically ill neonates. 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 “indomethacin” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for indomethacin in the PubMed Central database: •

Combined Treatment with Interleukin-12 and Indomethacin Promotes Increased Resistance in BALB/c Mice with Established Leishmania major Infections. by Li J, Padigel UM, Scott P, Farrell JP.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128357

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Effect of indomethacin on the incidence of experimental Escherichia coli pyelonephritis. by Glauser MP, Francioli PB, Bille J, Bonard M, Meylan P.; 1983 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264887

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Effects of gamma interferon and indomethacin in preventing Brucella abortus infections in mice. by Stevens MG, Pugh GW Jr, Tabatabai LB.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257479

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Effects of Indomethacin on Acute, Subacute, and Latent Infections in Mice and Rats. by Robinson HJ, Phares HF, Graessle OE.; 1968 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252246

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Effects of indomethacin on ovarian leukocytes during the periovulatory period in the rat. by Gaytan F, Morales C, Bellido C, Tarradas E, Eugenio Sanchez-Criado J.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151798

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Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release. by Raud J, Dahlen SE, Sydbom A, Lindbom L, Hedqvist P.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279982

3 4

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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Increased sensitivity of Corynebacterium parvum-treated mice to toxic effects of indomethacin and lipopolysaccharide. by Hart DA.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263184

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Indomethacin promotes differentiation of Trypanosoma brucei. by Jack RM, Black SJ, Reed SL, Davis CE.; 1984 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263462

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Influence of indomethacin on the intrarenal uptake of gentamicin in endotoxemic rats. by Bergeron MG, Bergeron Y, Tardif M, Marchand S, Beauchamp D.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172651

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Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen cells to secrete prostaglandin E2, and indomethacin upregulates immune functions. by Fitzgerald TJ, Tomai MA, Trachte GJ, Rice T.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257718

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Renal disposition of ceftazidime illustrated by interferences by probenecid, furosemide, and indomethacin in rabbits. by Carbon C, Dromer F, Brion N, Cremieux AC, Contrepois A.; 1984 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176173

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Reversal of lipopolysaccharide-analog-induced antibody suppression by antitransforming growth factor beta and indomethacin. by Odean MJ, Johnson AG, Mohrman M, Hasegawa A.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173314

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Use of indomethacin to demonstrate enterotoxic activity in extracts of Entamoeba histolytica trophozoites. by Udezulu IA, Leitch GJ, Bailey GB.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351299

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Zidovudine Azido-Reductase in Human Liver Microsomes: Activation by Ethacrynic Acid, Dipyridamole, and Indomethacin and Inhibition by Human Immunodeficiency Virus Protease Inhibitors. by Fayz S, Inaba T.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105661

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 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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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 indomethacin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “indomethacin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for indomethacin (hyperlinks lead to article summaries): •

A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. Author(s): Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K, Langhendries JP. Source: The New England Journal of Medicine. 2000 September 7; 343(10): 674-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10974130

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A comparison of oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in preterm infants. Author(s): Chotigeat U, Jirapapa K, Layangkool T. Source: J Med Assoc Thai. 2003 August; 86 Suppl 3: S563-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700149

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A double-blind randomized study of fetal side effects during and after the short-term maternal administration of indomethacin, sulindac, and nimesulide for the treatment of preterm labor. Author(s): Sawdy RJ, Lye S, Fisk NM, Bennett PR. Source: American Journal of Obstetrics and Gynecology. 2003 April; 188(4): 1046-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12712108

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A patient with cluster headache responsive to indomethacin: any relationship with chronic paroxysmal hemicrania? Author(s): Buzzi MG, Formisano R. Source: Cephalalgia : an International Journal of Headache. 2003 June; 23(5): 401-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780773

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A preliminary study on pharmacokinetics of oral indomethacin in premature infants in north India. Author(s): Sharma PK, Garg SK, Narang A. Source: The Indian Journal of Medical Research. 2003 April; 117: 164-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604305

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A retrospective study of the effect of postoperative indomethacin rectal suppositories on the need for narcotic analgesia in patients who had a cesarean delivery while they were under regional anesthesia. Author(s): Ambrose FP. Source: American Journal of Obstetrics and Gynecology. 2001 June; 184(7): 1544-7; Discussion 1547-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408878

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Activation of peroxisome proliferator-activated receptor gamma does not explain the antiproliferative activity of the nonsteroidal anti-inflammatory drug indomethacin on human colorectal cancer cells. Author(s): Hawcroft G, Gardner SH, Hull MA. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 May; 305(2): 632-7. Epub 2003 February 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606626

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Activity of the non-steroidal anti-inflammatory drug indomethacin against colorectal cancer. Author(s): Hull MA, Gardner SH, Hawcroft G. Source: Cancer Treatment Reviews. 2003 August; 29(4): 309-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927571

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Allergic contact dermatitis due to indomethacin and diclofenac. Author(s): Gomez A, Florido JF, Quiralte J, Martin AE, Saenz de San Pedro B. Source: Contact Dermatitis. 2000 July; 43(1): 59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10902602

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Allergic contact dermatitis from indomethacin. Author(s): Pulido Z, Gonzalez E, Alfaya T, Alvarez JA, Cena M, de la Hoz B. Source: Contact Dermatitis. 1999 August; 41(2): 112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10445701

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An evidence-based approach to predicting low IQ in very preterm infants from the neurological examination: outcome data from the indomethacin Indomethacin Intraventricular Hemorrhage Prevention Trial. Author(s): Pleacher MD, Vohr BR, Katz KH, Ment LR, Allan WC. Source: Pediatrics. 2004 February; 113(2): 416-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14754962

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Angiotensin II in human veins: development of rapid desensitization and effect of indomethacin. Author(s): Harada K, Ohmori M, Kitoh Y, Sugimoto K, Fujimura A. Source: Clinical and Experimental Pharmacology & Physiology. 1999 December; 26(12): 959-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10626062

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Anti-lymphoma effect of naproxen and indomethacin in a patient with relapsed diffuse large B-cell lymphoma. Author(s): Yoshinaga K, Teramura M, Iwabe K, Kobayashi S, Masuda M, Motoji T, Mizoguchi H. Source: American Journal of Hematology. 2001 March; 66(3): 220-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279630

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Aspirin and indomethacin exhibit antiproliferative effects and induce apoptosis in T98G human glioblastoma cells. Author(s): Amin R, Kamitani H, Sultana H, Taniura S, Islam A, Sho A, Ishibashi M, Eling TE, Watanabe T. Source: Neurological Research. 2003 June; 25(4): 370-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870263

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Bartter syndrome in a neonate: early treatment with indomethacin. Author(s): Mourani CC, Sanjad SA, Akatcherian CY. Source: Pediatric Nephrology (Berlin, Germany). 2000 February; 14(2): 143-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10684365

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Bioavailability studies on fast release formulations of indomethacin. Author(s): Verma MM, Kumar MT, Balasubramaniam J, Pandit JK. Source: Boll Chim Farm. 2002 May-June; 141(3): 176-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12197414

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Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin? Author(s): Locatelli A, Vergani P, Bellini P, Strobelt N, Ghidini A. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 March; 108(3): 325-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11281476

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Can dopamine prevent the renal side effects of indomethacin? A prospective randomized clinical study. Author(s): Baenziger O, Waldvogel K, Ghelfi D, Arbenz U, Fanconi S. Source: Klinische Padiatrie. 1999 November-December; 211(6): 438-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10592922

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Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin. Author(s): Christmann V, Liem KD, Semmekrot BA, van de Bor M. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(4): 440-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061361

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Chronic bilateral headache responding to indomethacin. Author(s): Hannerz J. Source: Headache. 2000 November-December; 40(10): 840-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11135030

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Chronic daily bilateral headache responsive to indomethacin. Author(s): Solomon S, Newman LC. Source: Headache. 1999 November-December; 39(10): 754-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279952

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Colchicine and indomethacin for the treatment of relapsing polychondritis. Author(s): Mark KA, Franks AG Jr. Source: Journal of the American Academy of Dermatology. 2002 February; 46(2 Suppl Case Reports): S22-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807462

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Combined indomethacin/gentamicin eyedrops to reduce pain after traumatic corneal abrasion. Author(s): Alberti MM, Bouat CG, Allaire CM, Trinquand CJ. Source: Eur J Ophthalmol. 2001 July-September; 11(3): 233-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11681501

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Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants. Author(s): Su PH, Chen JY, Su CM, Huang TC, Lee HS. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 December; 45(6): 665-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651538

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Cost-effectiveness of prophylactic indomethacin in very-low-birth-weight infants. Author(s): Moya MP, Goldberg RN. Source: The Annals of Pharmacotherapy. 2002 February; 36(2): 218-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11847937

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Cough headache associated with Chiari type-I malformation: responsiveness to indomethacin. Author(s): Ertsey C, Jelencsik I. Source: Cephalalgia : an International Journal of Headache. 2000 June; 20(5): 518-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11037749

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COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin. Author(s): Sigthorsson G, Crane R, Simon T, Hoover M, Quan H, Bolognese J, Bjarnason I. Source: Gut. 2000 October; 47(4): 527-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10986213

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Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. Author(s): Hirai H, Tanaka K, Takano S, Ichimasa M, Nakamura M, Nagata K. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 February 1; 168(3): 981-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801628

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Cyclic monoterpene extract from cardamom oil as a skin permeation enhancer for indomethacin: in vitro and in vivo studies. Author(s): Huang YB, Fang JY, Hung CH, Wu PC, Tsai YH. Source: Biological & Pharmaceutical Bulletin. 1999 June; 22(6): 642-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408241

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Decrease in nucleophosmin/B23 mRNA and telomerase activity during indomethacininduced apoptosis of gastric KATO-III cancer cells. Author(s): You BJ, Huang IJ, Liu WH, Hung YB, Chang JH, Yung BY. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1999 December; 360(6): 68390. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10619186

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Determination of indomethacin polymorphic contents by chemometric near-infrared spectroscopy and conventional powder X-ray diffractometry. Author(s): Otsuka M, Kato F, Matsuda Y. Source: The Analyst. 2001 September; 126(9): 1578-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592653

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Development of model aqueous ophthalmic solution of indomethacin. Author(s): Dimitrova E, Bogdanova S, Mitcheva M, Tanev I, Minkov E. Source: Drug Development and Industrial Pharmacy. 2000 December; 26(12): 1297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11147131

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Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc. Author(s): Zhu GH, Wong BC, Ching CK, Lai KC, Lam SK. Source: Biochemical Pharmacology. 1999 July 1; 58(1): 193-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403534

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Differing mechanisms of inhibition of calcium increases in human uterine myocytes by indomethacin and nimesulide. Author(s): Landen CN Jr, Zhang P, Young RC. Source: American Journal of Obstetrics and Gynecology. 2001 May; 184(6): 1100-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11349169

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Distribution of indomethacin in human milk and estimation of its milk to plasma ratio in vitro. Author(s): Beaulac-Baillargeon L, Allard G. Source: British Journal of Clinical Pharmacology. 1993 November; 36(5): 413-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959288

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Do we need another NSAID instead of indomethacin for treatment of ductus arteriosus in preterm infants? Author(s): Leonhardt A, Seyberth HW. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 September; 92(9): 996-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599056

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Don't discard your indomethacin yet. Author(s): Cotton RB. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 November; 89(11): 1278-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106035

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Dopamine versus no treatment to prevent renal dysfunction in indomethacin-treated preterm newborn infants. Author(s): Barrington K, Brion LP. Source: Cochrane Database Syst Rev. 2002; (3): Cd003213. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137683

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Doppler sonographic study of the effect of indomethacin on cardiac and pulmonary hemodynamics of the preterm infant. Author(s): Benders MJ, van de Bor M, van Bel F. Source: European Journal of Ultrasound : Official Journal of the European Federation of Societies for Ultrasound in Medicine and Biology. 1999 May; 9(2): 107-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10413746

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Dose, efficacy and tolerability of long-term indomethacin treatment of chronic paroxysmal hemicrania and hemicrania continua. Author(s): Pareja JA, Caminero AB, Franco E, Casado JL, Pascual J, Sanchez del Rio M. Source: Cephalalgia : an International Journal of Headache. 2001 November; 21(9): 90610. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903285

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Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome. Author(s): Van Overmeire B, Van de Broek H, Van Laer P, Weyler J, Vanhaesebrouck P. Source: The Journal of Pediatrics. 2001 February; 138(2): 205-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11174617

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Early versus late treatment of PDA with indomethacin. Author(s): Wadhawan R, Rubin LP. Source: The Journal of Pediatrics. 2002 April; 140(4): 487-8; Author Reply 488-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006972

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Echocardiographic flow pattern of patent ductus arteriosus: a guide to indomethacin treatment in premature infants. Author(s): Su BH, Peng CT, Tsai CH. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1999 November; 81(3): F197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10525023

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Effect of age and birth weight on indomethacin pharmacodynamics in neonates treated for patent ductus arteriosus. Author(s): Shaffer CL, Gal P, Ransom JL, Carlos RQ, Smith MS, Davey AM, Dimaguila MA, Brown YL, Schall SA. Source: Critical Care Medicine. 2002 February; 30(2): 343-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11889306

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Effect of early targeted indomethacin on the ductus arteriosus and blood flow to the upper body and brain in the preterm infant. Author(s): Osborn DA, Evans N, Kluckow M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 November; 88(6): F477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602694

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Effect of high dose ramipril with or without indomethacin on glomerular selectivity. Author(s): Pisoni R, Ruggenenti P, Sangalli F, Lepre MS, Remuzzi A, Remuzzi G. Source: Kidney International. 2002 September; 62(3): 1010-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164885

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Effect of indomethacin on amniotic fluid prostaglandin and aldosterone levels in a fetus with Bartter syndrome. Author(s): Amsalem H, Valsky DV, Yagel S, Celnikier DH, Anteby EY. Source: Prenatal Diagnosis. 2003 May; 23(5): 431-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749044

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Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. Author(s): Spence JD. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 August; 14(8 Pt 1): 835. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11497204

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Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. Author(s): Morgan TO, Anderson A, Bertram D. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2000 November; 13(11): 1161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11078175

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Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients. Author(s): Conlin PR, Moore TJ, Swartz SL, Barr E, Gazdick L, Fletcher C, DeLucca P, Demopoulos L. Source: Hypertension. 2000 September; 36(3): 461-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988282

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Effect of indomethacin on IL-1beta, IL-6 and TNFalpha production by mononuclear cells of preterm newborns and adults. Author(s): Sirota L, Punsky I, Bessler H. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 March; 89(3): 331-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772282

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Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study. Author(s): Fogari R, Zoppi A, Carretta R, Veglio F, Salvetti A; Italian Collaborative Study Group. Source: Journal of Hypertension. 2002 May; 20(5): 1007-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011663

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Effect of inhaled indomethacin in asthmatic patients taking high doses of inhaled corticosteroids. Author(s): Tamaoki J, Nakata J, Nishimura K, Kondo M, Aoshiba K, Kawatani K, Nagai A. Source: The Journal of Allergy and Clinical Immunology. 2000 June; 105(6 Pt 1): 1134-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856147

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Effect of lysine modification on the conformation and indomethacin binding properties of human serum albumin. Author(s): Tayyab S, Haq SK, Sabeeha, Aziz MA, Khan MM, Muzammil S. Source: International Journal of Biological Macromolecules. 1999 November; 26(2-3): 173-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10517526

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Effect of patent ductus arteriosus and indomethacin treatment on serum cardiac troponin T levels in preterm infants with respiratory distress syndrome. Author(s): Trevisanuto D, Zaninotto M, Lachin M, Altinier S, Plebani M, Ferrarese P, Zanardo V. Source: European Journal of Pediatrics. 2000 April; 159(4): 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10789933

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Effect of the nonsteroidal anti-inflammatory drug indomethacin on proliferation and apoptosis of colon carcinoma cells. Author(s): Kralj M, Kapitanovic S, Kovacevic D, Lukac J, Spaventi S, Pavelic K. Source: Journal of Cancer Research and Clinical Oncology. 2001; 127(3): 173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11260862

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Effects of aspirin and indomethacin on endothelial cell proliferation in vitro. Author(s): Pearce HR, Kalia N, Bardhan KD, Brown NJ. Source: Journal of Gastroenterology and Hepatology. 2003 October; 18(10): 1180-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974906

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Effects of fluoxetine, indomethacine and placebo on 3 alpha, 5 alpha tetrahydroprogesterone (THP) plasma levels in uncomplicated alcohol withdrawal. Author(s): Romeo E, Pompili E, di Michele F, Pace M, Rupprecht R, Bernardi G, Pasinib A. Source: World J Biol Psychiatry. 2000 April; 1(2): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607205

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Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. Author(s): Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli FF. Source: The Journal of Pediatrics. 1999 December; 135(6): 733-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586177

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Effects of indomethacin on cerebral blood flow at rest and during hypercapnia: an arterial spin tagging study in humans. Author(s): St Lawrence KS, Ye FQ, Lewis BK, Weinberger DR, Frank JA, McLaughlin AC. Source: Journal of Magnetic Resonance Imaging : Jmri. 2002 June; 15(6): 628-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112512

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Effects of indomethacin on energy metabolism in rat and human jejunal tissue in vitro. Author(s): Jacob M, Bjarnason I, Simpson RJ. Source: Clinical Science (London, England : 1979). 2001 November; 101(5): 493-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11672454

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Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo. Author(s): Jacob M, Bjarnason I, Simpson RJ. Source: Clinical Science (London, England : 1979). 2002 May; 102(5): 541-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11980573

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Effects of indomethacin on the L-selectin expression in humans. Author(s): Dirnberger E, Albinni S, Roggla M, Jilma B. Source: Scandinavian Journal of Immunology. 2001 November; 54(5): 525-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11696205

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Effects of indomethacin suppository and lidocaine pomade for the relief of postepisiotomy pain. Author(s): Seckin B, Avsar F, Parlakyigit E, Aksakal O. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 August; 78(2): 159-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12175719

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Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Author(s): Rubin BR, Burton R, Navarra S, Antigua J, Londono J, Pryhuber KG, Lund M, Chen E, Najarian DK, Petruschke RA, Ozturk ZE, Geba GP. Source: Arthritis and Rheumatism. 2004 February; 50(2): 598-606. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872504

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Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial. Author(s): Di Monda V, Nicolodi M, Aloisio A, Del Bianco P, Fonzari M, Grazioli I, Uslenghi C, Vecchiet L, Sicuteri F. Source: Headache. 2003 September; 43(8): 835-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940804

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Efficacy of indomethacin 0.1% and fluorometholone 0.1% on conjunctival inflammation following chronic application of antiglaucomatous drugs. Author(s): Baudouin C, Nordmann JP, Denis P, Creuzot-Garcher C, Allaire C, Trinquand C. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 November; 240(11): 929-35. Epub 2002 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486516

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Enhanced inhibition of platelet aggregation in-vitro by niosome-encapsulated indomethacin. Author(s): Pillai GK, Salim ML. Source: International Journal of Pharmaceutics. 1999 December 20; 193(1): 123-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10581429

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Eosinophilic pustular folliculitis (Ofuji's disease): indomethacin as a first choice of treatment. Author(s): Ota T, Hata Y, Tanikawa A, Amagai M, Tanaka M, Nishikawa T. Source: Clinical and Experimental Dermatology. 2001 March; 26(2): 179-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298111

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Epidural injections of indomethacin for postlaminectomy syndrome: a preliminary report. Author(s): Aldrete JA. Source: Anesthesia and Analgesia. 2003 February; 96(2): 463-8, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538197

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Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors. Author(s): Kalgutkar AS, Marnett AB, Crews BC, Remmel RP, Marnett LJ. Source: Journal of Medicinal Chemistry. 2000 July 27; 43(15): 2860-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10956194

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Evaluation of chronopharmacodynamics of indomethacin by the kaolin-induced pain model in mice. Author(s): Cui Y, Sugimoto K, Araki N, Fujimura A. Source: Chronobiology International. 2003 May; 20(3): 473-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868542

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Evaluation of long-term treatment with indomethacin in hereditary hypokalemic saltlosing tubulopathies. Author(s): Reinalter SC, Grone HJ, Konrad M, Seyberth HW, Klaus G. Source: The Journal of Pediatrics. 2001 September; 139(3): 398-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11562620

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Evaluation of Tanacetum larvatum for an anti-inflammatory activity and for the protection against indomethacin-induced ulcerogenesis in rats. Author(s): Petrovic SD, Dobric S, Bokonjic D, Niketic M, Garcia-Pineres A, Merfort I. Source: Journal of Ethnopharmacology. 2003 July; 87(1): 109-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787963

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Evaluation of the analgesic effect of 0.1% indomethacin solution on corneal abrasions. Author(s): Patrone G, Sacca SC, Macri A, Rolando M. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 1999; 213(6): 350-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10567865

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Evaluation of the inhibitory activity of topical indomethacin, betamethasone valerate and emollients on UVL-induced inflammation by means of non-invasive measurements of the skin elasticity. Author(s): Dobrev H. Source: Photodermatology, Photoimmunology & Photomedicine. 2001 August; 17(4): 184-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499541

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Exposure of human breast cancer cells to the anti-inflammatory agent indomethacin alters choline phospholipid metabolites and Nm23 expression. Author(s): Natarajan K, Mori N, Artemov D, Bhujwalla ZM. Source: Neoplasia (New York, N.Y.). 2002 September-October; 4(5): 409-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12192599

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Factors associated with permanent closure of the ductus arteriosus: a role for prolonged indomethacin therapy. Author(s): Quinn D, Cooper B, Clyman RI. Source: Pediatrics. 2002 July; 110(1 Pt 1): E10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093991

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Factors influencing successful closure with indomethacin of the patent ductus arteriosus in premature infants. Author(s): Kalis NN, Pieper C, van der Merwe PL, Nel ED. Source: Cardiovasc J S Afr. 2001 October-November; 12(5): 268-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753466

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Furosemide for symptomatic patent ductus arteriosus in indomethacin-treated infants. Author(s): Brion LP, Campbell DE. Source: Cochrane Database Syst Rev. 2001; (3): Cd001148. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11686979

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Furosemide for symptomatic patent ductus arteriosus in indomethacin-treated infants. Author(s): Cochrane Database Syst Rev. 2001;(2):CD001454 Source: Cochrane Database Syst Rev. 2000; (2): Cd001148. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11405991

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Gastroesophageal endoscopic findings and gastrointestinal symptoms in preterm neonates with and without perinatal indomethacin exposure. Author(s): Ojala R, Ruuska T, Karikoski R, Ikonen RS, Tammela O. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 February; 32(2): 182-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11321390

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Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis. Author(s): Boushey RP, Yusta B, Drucker DJ. Source: The American Journal of Physiology. 1999 November; 277(5 Pt 1): E937-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10567023

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Hemicrania continua: an indomethacin-responsive case with an underlying malignant etiology. Author(s): Eross EJ, Swanson JW, Dodick DW. Source: Headache. 2002 June; 42(6): 527-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167144

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Hemicrania with response to indomethacin and prevalent autonomic symptoms: four cases. Author(s): Donnet A, Lucas C, Massardier E, Boulliat J. Source: Cephalalgia : an International Journal of Headache. 2003 March; 23(2): 157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603375

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Heterotopic ossification prophylaxis with indomethacin increases the risk of longbone nonunion. Author(s): Burd TA, Hughes MS, Anglen JO. Source: The Journal of Bone and Joint Surgery. British Volume. 2003 July; 85(5): 700-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892193

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Hexokinase translocation during neutrophil activation, chemotaxis, and phagocytosis: disruption by cytochalasin D, dexamethasone, and indomethacin. Author(s): Huang JB, Kindzelskii AL, Petty HR. Source: Cellular Immunology. 2002 July-August; 218(1-2): 95-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12470617

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How can one apply rescue indomethacin therapy to a 1-month-old baby with antenatal Bartter syndrome in the case of severe vomiting? Author(s): Proesmans W. Source: Pediatric Nephrology (Berlin, Germany). 2001 June; 16(6): 532. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11420924

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Hypnic headache: another indomethacin-responsive headache syndrome? Author(s): Dodick DW, Jones JM, Capobianco DJ. Source: Headache. 2000 November-December; 40(10): 830-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11135028

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Ibuprofen as effective as indomethacin for patent ductus arteriosus. Author(s): SoRelle R. Source: Circulation. 2000 July 25; 102(4): E9007-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10908230

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Ibuprofen versus indomethacin for closure of patent ductus arteriosus. Author(s): Casalaz D. Source: The New England Journal of Medicine. 2001 February 8; 344(6): 457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11221607

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Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. Author(s): Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Source: Jama : the Journal of the American Medical Association. 2003 March 5; 289(9): 1124-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622582

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In partial defense of prolonged indomethacin therapy for patent ductus arteriosus. Author(s): Hammerman C. Source: The Journal of Pediatrics. 2000 May; 136(5): 707-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10802512

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In vitro growth inhibition by indomethacin on human oral squamous cell carcinoma lines synergistically suppressed by all-trans retinoic acid correlating to apoptosis. Author(s): Yang CC, Tu SF, Wu CH, Chang RC, Kao SY. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 December; 65(12): 600-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636206

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Incidence and outcome of a 10-fold indomethacin overdose in premature infants. Author(s): Narayanan M, Schlueter M, Clyman RI. Source: The Journal of Pediatrics. 1999 July; 135(1): 105-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393614

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Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion. Author(s): Al-Waili NS. Source: Bju International. 2002 August; 90(3): 294-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133068

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Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action. Author(s): Puscas I, Ifrim M, Maghiar T, Coltau M, Domuta G, Baican M, Hecht A. Source: Int J Clin Pharmacol Ther. 2001 June; 39(6): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430635

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Indomethacin activity in the fetal vasculature of normal and meconium exposed human placentae. Author(s): Holcberg G, Sapir O, Huleihel M, Katz M, Bashiri A, Mazor M, Malek A, Tsadkin M, Schneider H. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 February; 94(2): 230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11165730

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Indomethacin and corticosteroids: an additive constrictive effect on the fetal ductus arteriosus. Author(s): Levy R, Matitiau A, Ben Arie A, Milman D, Or Y, Hagay Z. Source: American Journal of Perinatology. 1999; 16(8): 379-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772195

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Indomethacin and cyclosporin a inhibit in vitro ischemia-induced expression of ICAM-1 and chemokines in human brain endothelial cells. Author(s): Zhang W, Smith C, Monette R, Hutchison J, Stanimirovic DB. Source: Acta Neurochir Suppl. 2000; 76: 47-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11450070

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Indomethacin and ibuprofen effect on IL-1ra production by mononuclear cells of preterm newborns and adults. Author(s): Bessler H, Ziyada S, Bergman M, Punsky I, Sirota L. Source: Biology of the Neonate. 2002 August; 82(2): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169827

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Indomethacin and ibuprofen induce Hsc70 nuclear localization and activation of the heat shock response in HeLa cells. Author(s): Lagunas L, Bradbury CM, Laszlo A, Hunt CR, Gius D. Source: Biochemical and Biophysical Research Communications. 2004 January 23; 313(4): 863-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706622

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Indomethacin and telomerase activity in tumor growth retardation. Author(s): Lonnroth C, Andersson M, Lundholm K. Source: International Journal of Oncology. 2001 May; 18(5): 929-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295037

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Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils. Author(s): Stubbs VE, Schratl P, Hartnell A, Williams TJ, Peskar BA, Heinemann A, Sabroe I. Source: The Journal of Biological Chemistry. 2002 July 19; 277(29): 26012-20. Epub 2002 April 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11980903

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Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures. Author(s): Burd TA, Lowry KJ, Anglen JO. Source: The Journal of Bone and Joint Surgery. American Volume. 2001 December; 83A(12): 1783-8. Erratum In: J Bone Joint Surg Am 2002 January; 84-A(1): 100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11741055

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Indomethacin decreases insulin secretion in patients with type 2 diabetes mellitus. Author(s): Pereira Arias AM, Romijn JA, Corssmit EP, Ackermans MT, Nijpels G, Endert E, Sauerwein HP. Source: Metabolism: Clinical and Experimental. 2000 July; 49(7): 839-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10909992

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Indomethacin delays gastric restitution: association with the inhibition of focal adhesion kinase and tensin phosphorylation and reduced actin stress fibers. Author(s): Szabo IL, Pai R, Jones MK, Ehring GR, Kawanaka H, Tarnawski AS. Source: Experimental Biology and Medicine (Maywood, N.J.). 2002 June; 227(6): 412-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037131

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Indomethacin does not affect endogenous glucose production in type 2 diabetes mellitus. Author(s): Pereira Arias AM, Bisschop PH, Ackermans MT, Endert E, Romijn JA, Sauerwein HP. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 November; 33(11): 659-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733868

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Indomethacin does not influence natural cell-mediated cytotoxic response to endurance exercise. Author(s): Braun WA, Flynn MG, Jacks DE, McLoughlin T, Sowash J, Lambert CP, Mylona E. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1999 December; 87(6): 2237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10601173

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Indomethacin for 3 days is not effective as prophylaxis for heterotopic ossification after primary total hip arthroplasty. Author(s): van der Heide HJ, Koorevaar RT, Schreurs BW, van Kampen A, Lemmens A. Source: The Journal of Arthroplasty. 1999 October; 14(7): 796-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10537252

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Indomethacin for asymptomatic patent ductus arteriosus in preterm infants. Author(s): Cooke L, Steer P, Woodgate P. Source: Cochrane Database Syst Rev. 2003; (2): Cd003745. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804488

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Indomethacin for brain edema following stroke. Author(s): Schwarz S, Bertram M, Aschoff A, Schwab S, Hacke W. Source: Cerebrovascular Diseases (Basel, Switzerland). 1999 July-August; 9(4): 248-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393414

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Indomethacin for preterm labor: a randomized comparison of vaginal and rectal-oral routes. Author(s): Abramov Y, Nadjari M, Weinstein D, Ben-Shachar I, Plotkin V, Ezra Y. Source: Obstetrics and Gynecology. 2000 April; 95(4): 482-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725476

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Indomethacin for the treatment of Alzheimer's disease patients. Author(s): Tabet N, Feldman H. Source: Cochrane Database Syst Rev. 2002; (2): Cd003673. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076498

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Indomethacin improves oxygen-induced retinopathy in the mouse. Author(s): Nandgaonkar BN, Rotschild T, Yu K, Higgins RD. Source: Pediatric Research. 1999 August; 46(2): 184-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10447113

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Indomethacin increases 15-PGDH mRNA expression in HL60 cells differentiated by PMA. Author(s): Frenkian M, Pidoux E, Baudoin C, Segond N, Jullienne A. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2001 February; 64(2): 87-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11237475

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Indomethacin increases the cytotoxicity of cis-platinum and 5-fluorouracil in the human uterine cervical cancer cell lines SKG-2 and HKUS by increasing the intracellular uptake of the agents. Author(s): Ogino M, Minoura S. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2001 April; 6(2): 84-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11706755

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Indomethacin induced avascular necrosis of head of femur. Author(s): Prathapkumar KR, Smith I, Attara GA. Source: Postgraduate Medical Journal. 2000 September; 76(899): 574-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10964124

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Indomethacin induced bulky lymphadenopathy and eosinophilic pneumonia. Author(s): Oishi Y, Sando Y, Tajima S, Maeno T, Maeno Y, Sato M, Hosono T, Suga T, Kurabayashi M, Nagai R. Source: Respirology (Carlton, Vic.). 2001 March; 6(1): 57-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11264764

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Indomethacin induced psychosis. Author(s): Tharumaratnam D, Bashford S, Khan SA. Source: Postgraduate Medical Journal. 2000 November; 76(901): 736-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11060173

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Indomethacin induces apoptosis and inhibits proliferation in chronic myeloid leukemia cells. Author(s): Zhang G, Tu C, Zhang G, Zhou G, Zheng W. Source: Leukemia Research. 2000 May; 24(5): 385-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10785260

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Indomethacin induces differential expression of beta-catenin, gamma-catenin and Tcell factor target genes in human colorectal cancer cells. Author(s): Hawcroft G, D'Amico M, Albanese C, Markham AF, Pestell RG, Hull MA. Source: Carcinogenesis. 2002 January; 23(1): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756231

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Indomethacin lowers the threshold thermal exposure for hyperthermic radiosensitization and heat-shock inhibition of ionizing radiation-induced activation of NF-kappaB. Author(s): Locke JE, Bradbury CM, Wei SJ, Shah S, Rene LM, Clemens RA, Roti Roti J, Horikoshi N, Gius D. Source: International Journal of Radiation Biology. 2002 June; 78(6): 493-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065054

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Indomethacin modulates circulating cytokine responses to strenuous exercise in humans. Author(s): Rhind SG, Gannon GA, Shephard RJ, Shek PN. Source: Cytokine. 2002 August 7; 19(3): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242082

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Indomethacin prophylaxis for patent ductus arteriosus (PDA) in infants with a birth weight of less than 1250 grams. Author(s): Supapannachart S, Khowsathit P, Patchakapati B. Source: J Med Assoc Thai. 1999 November; 82 Suppl 1: S87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10730525

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Indomethacin reduces CSF pressure in intracranial hypertension. Author(s): Forderreuther S, Straube A. Source: Neurology. 2000 October 10; 55(7): 1043-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061268

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Indomethacin reduces lung adenoma number in A/J mice. Author(s): Moody TW, Leyton J, Zakowicz H, Hida T, Kang Y, Jakowlew S, You L, Ozbun L, Zia H, Youngberg J, Malkinson A. Source: Anticancer Res. 2001 May-June; 21(3B): 1749-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11497255

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Indomethacin responsiveness of patent ductus arteriosus and renal abnormalities in preterm infants treated with indomethacin. Author(s): Itabashi K, Ohno T, Nishida H. Source: The Journal of Pediatrics. 2003 August; 143(2): 203-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970633

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Indomethacin therapy in hydramnios. Author(s): Abhyankar S, Salvi VS. Source: Journal of Postgraduate Medicine. 2000 July-September; 46(3): 176-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298464

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Indomethacin therapy in the treatment of polyhydramnios due to placental chorioangioma. Author(s): Kriplani A, Abbi M, Banerjee N, Roy KK, Takkar D. Source: The Journal of Obstetrics and Gynaecology Research. 2001 October; 27(5): 245-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776505

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Indomethacin tocolysis and intraventricular hemorrhage. Author(s): Suarez RD, Grobman WA, Parilla BV. Source: Obstetrics and Gynecology. 2001 June; 97(6): 921-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11384697

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Indomethacin tocolysis and risk of necrotizing enterocolitis. Author(s): Parilla BV, Grobman WA, Holtzman RB, Thomas HA, Dooley SL. Source: Obstetrics and Gynecology. 2000 July; 96(1): 120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862854

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Indomethacin treatment decreases renal blood flow velocity in human neonates. Author(s): Kang NS, Yoo KH, Cheon H, Choi BM, Hong YS, Lee JW, Kim SK. Source: Biology of the Neonate. 1999 November; 76(5): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10516392

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Indomethacin treatment of infantile cortical periostosis in twins. Author(s): Couper RT, McPhee A, Morris L. Source: Journal of Paediatrics and Child Health. 2001 June; 37(3): 305-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11468051

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Indomethacin versus meloxicam for prevention of heterotopic ossification after total hip arthroplasty. Author(s): Legenstein R, Bosch P, Ungersbock A. Source: Archives of Orthopaedic and Trauma Surgery. 2003 April; 123(2-3): 91-4. Epub 2003 March 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12664317

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Indomethacin versus radiation therapy for heterotopic ossification after hip arthroplasty. Author(s): D'Lima DD, Venn-Watson EJ, Tripuraneni P, Colwell CW. Source: Orthopedics. 2001 December; 24(12): 1139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11770090

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Indomethacin, a cox inhibitor, enhances 15-PGDH and decreases human tumoral C cells proliferation. Author(s): Frenkian M, Segond N, Pidoux E, Cohen R, Jullienne A. Source: Prostaglandins & Other Lipid Mediators. 2001 May; 65(1): 11-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352223

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Indomethacin: a review of its cerebral blood flow effects and potential use for controlling intracranial pressure in traumatic brain injury patients. Author(s): Slavik RS, Rhoney DH. Source: Neurological Research. 1999 July; 21(5): 491-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10439431

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Indomethacin: continuous versus bolus administration. Author(s): Cotton RB. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(4): 369-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061347

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Indomethacin-induced apoptosis in esophageal adenocarcinoma cells involves upregulation of Bax and translocation of mitochondrial cytochrome C independent of COX-2 expression. Author(s): Aggarwal S, Taneja N, Lin L, Orringer MB, Rehemtulla A, Beer DG. Source: Neoplasia (New York, N.Y.). 2000 July-August; 2(4): 346-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11005569

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Indomethacin-induced disturbances in villous microcirculation in the rat ileum. Author(s): Ruh J, Schmidt E, Vogel F, Klar E. Source: Microvascular Research. 1999 September; 58(2): 137-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458929

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Indomethacin-induced postoperative psychosis. Author(s): Nassif JM, Ritter MA. Source: The Journal of Arthroplasty. 1999 September; 14(6): 769-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10512453

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Indomethacin-induced radiosensitization and inhibition of ionizing radiationinduced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase. Author(s): Bradbury CM, Markovina S, Wei SJ, Rene LM, Zoberi I, Horikoshi N, Gius D. Source: Cancer Research. 2001 October 15; 61(20): 7689-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11606413

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Indomethacin-induced rectovaginal fistula in a postpartum patient. Author(s): Abdul-Wahid FS, Qureshi A, Soon-Keng C. Source: Diseases of the Colon and Rectum. 2002 June; 45(6): 843-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072643

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Indomethacin-responsive headaches in children and adolescents. Author(s): Moorjani BI, Rothner AD. Source: Semin Pediatr Neurol. 2001 March; 8(1): 40-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11332865

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Inhaled indomethacin in bronchorrhea in bronchioloalveolar carcinoma: role of cyclooxygenase. Author(s): Tamaoki J, Kohri K, Isono K, Nagai A. Source: Chest. 2000 April; 117(4): 1213-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10767270

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Inhibition of cyclooxygenase by indomethacin modulates osteoblast response to titanium surface roughness in a time-dependent manner. Author(s): Sisk MA, Lohmann CH, Cochran DL, Sylvia VL, Simpson JP, Dean DD, Boyan BD, Schwartz Z. Source: Clinical Oral Implants Research. 2001 February; 12(1): 52-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168271

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Interaction of indomethacin with cytokine production in whole blood. Potential mechanism for a brain-protective effect. Author(s): Bour AM, Westendorp RG, Laterveer JC, Bollen EL, Remarque EJ. Source: Experimental Gerontology. 2000 October; 35(8): 1017-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11121687

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Intractable hypoglycemia following indomethacin therapy for patent ductus arteriosus. Author(s): Hosono S, Ohno T, Ojima K, Kimoto H, Nagoshi R, Shimizu M, Nozawa M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2000 August; 42(4): 372-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10986869

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Intravenous indomethacin for preventing mortality and morbidity in very low birth weight infants. Author(s): Cochrane Database Syst Rev. 2001;(3):CD001148 Source: Cochrane Database Syst Rev. 2000; (2): Cd000174. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11686979

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Is indomethacin or ibuprofen better for medical closure of the patent ductus arteriosus? Author(s): Swartz EN. Source: Archives of Disease in Childhood. 2003 December; 88(12): 1134-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670792

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LASH: a syndrome of long-lasting autonomic symptoms with hemicrania (A new indomethacin- responsive headache). Author(s): Rozen TD. Source: Headache. 2000 June; 40(6): 483-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10849046

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Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. Author(s): Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S, Solimano A, Vincer M, Wright LL; Trial of Indomethacin Prophylaxis in Preterms Investigators. Source: The New England Journal of Medicine. 2001 June 28; 344(26): 1966-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430325

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Low-dose continuous indomethacin in early days of age reduce the incidence of symptomatic patent ductus arteriosus without adverse effects. Author(s): Nakamura T, Tamura M, Kadowaki S, Sasano T. Source: American Journal of Perinatology. 2000; 17(5): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110346

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Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F(2alpha) and indomethacin. Author(s): Ulug U, Goldman S, Ben-Shlomo I, Shalev E. Source: Molecular Human Reproduction. 2001 December; 7(12): 1187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11719597

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Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation. Author(s): St Lawrence KS, Ye FQ, Lewis BK, Frank JA, McLaughlin AC. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2003 July; 50(1): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815684

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Meloxicam and indomethacin activity on human matrix metalloproteinases in synovial fluid. Author(s): Barracchini A, Franceschini N, Minisola G, Pantaleoni GC, Di Giulio AD, Oratore A, Amicosante G. Source: Annals of the New York Academy of Sciences. 1999 June 30; 878: 665-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10415802

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Microcrystallization of indomethacin using a pH-shift method. Author(s): Kim ST, Kwon JH, Lee JJ, Kim CW. Source: International Journal of Pharmaceutics. 2003 September 16; 263(1-2): 141-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954189

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Minimal effective dose of indomethacin for the treatment of patent ductus arteriosus in preterm infants. Author(s): Dumas de la Roque E, Fayon M, Babre F, Demarquez JL, Pedespan L. Source: Biology of the Neonate. 2002; 81(2): 91-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844876

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Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and functional brain activation. Author(s): Bruhn H, Fransson P, Frahm J. Source: Journal of Magnetic Resonance Imaging : Jmri. 2001 March; 13(3): 325-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11241803

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Modulatory effects of indomethacin on androgen metabolism in human gingival and oral periosteal fibroblasts. Author(s): Tilakaratne A, Soory M. Source: Steroids. 2001 December; 66(12): 857-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711113

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Molecular basis of indomethacin-human serum albumin interaction. Author(s): Trivedi VD, Vorum H, Honore B, Qasim MA. Source: The Journal of Pharmacy and Pharmacology. 1999 May; 51(5): 591-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411219

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MUC5AC mucin release from human airways in vitro: effects of indomethacin and Bay X1005. Author(s): Roger P, Gascard JP, Bara J, de Montpreville VT, Brink C. Source: Mediators of Inflammation. 2001 February; 10(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11324902

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Necrotizing enterocolitis and gastrointestinal complications after indomethacin therapy and surgical ligation in premature infants with patent ductus arteriosus. Author(s): O'Donovan DJ, Baetiong A, Adams K, Chen A, Smith EO, Adams JM, Weisman LE. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2003 June; 23(4): 286-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774134

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Neonatal acute haemorrhagic gastritis and antenatal exposure to indomethacin for tocolysis. Author(s): Bolisetty S, Patole S, Koh G, Stalewski H, Whitehall J. Source: Anz Journal of Surgery. 2001 February; 71(2): 122-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11413591

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Neonatal necrotizing enterocolitis with intestinal perforation in extremely premature infants receiving early indomethacin treatment for patent ductus arteriosus. Author(s): Fujii AM, Brown E, Mirochnick M, O'Brien S, Kaufman G. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 October-November; 22(7): 535-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12368968

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Neonatal outcome after exposure to indomethacin in utero: a retrospective case cohort study. Author(s): Abbasi S, Gerdes JS, Sehdev HM, Samimi SS, Ludmir J. Source: American Journal of Obstetrics and Gynecology. 2003 September; 189(3): 782-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526313

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Neurodevelopmental follow-up at 36 months' corrected age of preterm infants treated with prophylactic indomethacin. Author(s): Couser RJ, Hoekstra RE, Ferrara TB, Wright GB, Cabalka AK, Connett JE. Source: Archives of Pediatrics & Adolescent Medicine. 2000 June; 154(6): 598-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10850507

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Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone. Author(s): Olsen NV, Jensen NG, Hansen JM, Christensen NJ, Fogh-Andersen N, Kanstrup IL. Source: Clinical Science (London, England : 1979). 1999 October; 97(4): 457-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10491346

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Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomized trial at Ramathibodi Hospital. Author(s): Supapannachart S, Limrungsikul A, Khowsathit P. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1252-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549803

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Outcome of children in the indomethacin intraventricular hemorrhage prevention trial. Author(s): Ment LR, Vohr B, Allan W, Westerveld M, Sparrow SS, Schneider KC, Katz KH, Duncan CC, Makuch RW. Source: Pediatrics. 2000 March; 105(3 Pt 1): 485-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10699097

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Parenteral indomethacin (the INDOTEST) in cluster headache. Author(s): Antonaci F, Costa A, Ghirmai S, Sances G, Sjaastad O, Nappi G. Source: Cephalalgia : an International Journal of Headache. 2003 April; 23(3): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12662186

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Patent ductus arteriosus in micropreemies and full-term infants: the relative merits of surgical ligation versus indomethacin treatment. Author(s): Little DC, Pratt TC, Blalock SE, Krauss DR, Cooney DR, Custer MD. Source: Journal of Pediatric Surgery. 2003 March; 38(3): 492-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632374

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Perinatal indomethacin treatment and neonatal complications in preterm infants. Author(s): Ojala R, Ikonen S, Tammela O. Source: European Journal of Pediatrics. 2000 March; 159(3): 153-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10664225

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Peroral sustained-release indomethacin treatment for rectal adenomas in familial adenomatous polyposis: a pilot study. Author(s): Akasu T, Yokoyama T, Sugihara K, Fujita S, Moriya Y, Kakizoe T. Source: Hepatogastroenterology. 2002 September-October; 49(47): 1259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239919

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Persistent Doppler flow predicts lack of response to multiple courses of indomethacin in premature infants with recurrent patent ductus arteriosus. Author(s): Keller RL, Clyman RI. Source: Pediatrics. 2003 September; 112(3 Pt 1): 583-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949288

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PGHS-2 inhibitors, NS-398 and DuP-697, attenuate the inhibition of PGHS-1 by aspirin and indomethacin without altering its activity. Author(s): Rosenstock M, Danon A, Rimon G. Source: Biochimica Et Biophysica Acta. 1999 August 25; 1440(1): 127-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10477832

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Phospholipid profiles of invasive human breast cancer cells are altered towards a less invasive phospholipid profile by the anti-inflammatory agent indomethacin. Author(s): Natarajan K, Mori N, Artemov D, Aboagye EO, Chacko VP, Bhujwalla ZM. Source: Advances in Enzyme Regulation. 2000; 40: 271-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10828355

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Prevention of deep-vein thrombosis after total knee arthroplasty in Asian patients. Comparison of low-molecular-weight heparin and indomethacin. Author(s): Wang CJ, Wang JW, Weng LH, Hsu CC, Huang CC, Yu PC. Source: The Journal of Bone and Joint Surgery. American Volume. 2004 January; 86-A(1): 136-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711956

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Prevention of heterotopic bone formation after total hip arthroplasty: a prospective randomised study comparing postoperative radiation therapy with indomethacin medication. Author(s): Kienapfel H, Koller M, Wust A, Sprey C, Merte H, Engenhart-Cabillic R, Griss P. Source: Archives of Orthopaedic and Trauma Surgery. 1999; 119(5-6): 296-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10447627

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Prevention of heterotopic ossification after spinal cord injury with indomethacin. Author(s): Banovac K, Williams JM, Patrick LD, Haniff YM. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 2001 July; 39(7): 370-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464310

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Prevention of heterotopic ossification after total hip replacement: a prospective comparison of indomethacin and salmon calcitonin in 60 patients. Author(s): Gunal I, Hazer B, Seber S, Gokturk E, Turgut A, Kose N. Source: Acta Orthopaedica Scandinavica. 2001 October; 72(5): 467-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728072

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Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus. Author(s): Hosono S, Ohono T, Kimoto H, Nagoshi R, Shimizu M, Nozawa M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 October; 43(5): 465-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737706

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Prophylactic indomethacin for preterm infants: a systematic review and metaanalysis. Author(s): Fowlie PW, Davis PG. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 November; 88(6): F464-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602691

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Prophylactic indomethacin reduces grades III and IV intraventricular hemorrhages when compared to early indomethacin treatment of a patent ductus arteriosus. Author(s): Yanowitz TD, Baker RW, Sobchak Brozanski B. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2003 June; 23(4): 317-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774141

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Prophylactic indomethacin: factors determining permanent ductus arteriosus closure. Author(s): Narayanan M, Cooper B, Weiss H, Clyman RI. Source: The Journal of Pediatrics. 2000 March; 136(3): 330-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10700689

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Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Author(s): Fowlie PW, Davis PG. Source: Cochrane Database Syst Rev. 2002; (3): Cd000174. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137607

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Prophylaxis of heterotopic ossification after total hip arthroplasty: a prospective randomized study comparing indomethacin and meloxicam. Author(s): Barthel T, Baumann B, Noth U, Eulert J. Source: Acta Orthopaedica Scandinavica. 2002 December; 73(6): 611-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553505

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Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD. Author(s): Douma CE, de Waart DR, Zemel D, Struijk DG, Krediet RT. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 April; 16(4): 803-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274278

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Psychiatric side effects of indomethacin in parturients. Author(s): Clunie M, Crone LA, Klassen L, Yip R. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 JuneJuly; 50(6): 586-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826551

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Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus. Author(s): Patel J, Roberts I, Azzopardi D, Hamilton P, Edwards AD. Source: Pediatric Research. 2000 January; 47(1): 36-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10625080

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Randomized trial of prolonged low-dose versus conventional-dose indomethacin for treating patent ductus arteriosus in very low birth weight infants. Author(s): Lee J, Rajadurai VS, Tan KW, Wong KY, Wong EH, Leong JY. Source: Pediatrics. 2003 August; 112(2): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897285

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Real-time changes in 1H and 31P NMR spectra of malignant human mammary epithelial cells during treatment with the anti-inflammatory agent indomethacin. Author(s): Glunde K, Ackerstaff E, Natarajan K, Artemov D, Bhujwalla ZM. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2002 November; 48(5): 819-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417996

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Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants. Author(s): Vermillion ST, Newman RB. Source: American Journal of Obstetrics and Gynecology. 1999 November; 181(5 Pt 1): 1083-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10561622

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Recovery of prostaglandin production associated with reopening of the ductus arteriosus after indomethacin treatment in preterm infants with respiratory distress syndrome. Author(s): Seyberth HW, Muller H, Wille L, Pluckthun H, Wolf D, Ulmer HE. Source: Pediatr Pharmacol (New York). 1982; 2(2): 127-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760405

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Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery. Author(s): Rapanos T, Murphy P, Szalai JP, Burlacoff L, Lam-McCulloch J, Kay J. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 August; 46(8): 725-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10451130

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Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacininduced expression of gamma-glutamylcysteine synthetase. Author(s): Sekhar KR, Spitz DR, Harris S, Nguyen TT, Meredith MJ, Holt JT, Gius D, Marnett LJ, Summar ML, Freeman ML, Guis D. Source: Free Radical Biology & Medicine. 2002 April 1; 32(7): 650-62. Erratum In: Free Radic Biol Med 2002 July 31; 33(1): 149. Guis David [corrected to Gius David]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909699

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Reduction in blood glucose values following indomethacin therapy for patent ductus arteriosus. Author(s): Hosono S, Ohno T, Kimoto H, Nagoshi R, Shimizu M, Nozawa M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 1999 October; 41(5): 525-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10530066

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Reduction of beta-catenin/T-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated beta-catenin. Author(s): Dihlmann S, Klein S, Doeberitz Mv MK. Source: Molecular Cancer Therapeutics. 2003 June; 2(6): 509-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12813129

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Regional hemodynamic effects of dopamine in the indomethacin-treated preterm infant. Author(s): Seri I, Abbasi S, Wood DC, Gerdes JS. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 June; 22(4): 300-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032793

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Regrowth of 5-fluorouracil-treated human colon cancer cells is prevented by the combination of interferon gamma, indomethacin, and phenylbutyrate. Author(s): Huang Y, Horvath CM, Waxman S. Source: Cancer Research. 2000 June 15; 60(12): 3200-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10866311

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Renal follow up of premature infants with and without perinatal indomethacin exposure. Author(s): Ojala R, Ala-Houhala M, Ahonen S, Harmoinen A, Turjanmaa V, Ikonen S, Tammela O. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2001 January; 84(1): F28-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11124920

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Renal tubular dysgenesis-like lesions and hypocalvaria. Report of two cases involving indomethacin. Author(s): Robin YM, Reynaud P, Orliaguet T, Lemery D, Vanlieferingen P, Dechelotte P. Source: Pathology, Research and Practice. 2000; 196(11): 791-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186177

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Resistive index in patients with renal colic: differences after medical treatment with indomethacin and ketorolac. Author(s): Bertolotto M, Quaia E, Gasparini C, Calderan L, Pozzi Mucelli R. Source: Radiol Med (Torino). 2003 October; 106(4): 370-5. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612828

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Reversible fetal hydrops associated with indomethacin use. Author(s): Pratt L, Digiosia J, Swenson JN, Trampe B, Martin CB Jr. Source: Obstetrics and Gynecology. 1997 October; 90(4 Pt 2): 676-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11770593

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Risk of persistent renal insufficiency in premature infants following the prenatal use of indomethacin for suppression of preterm labor. Author(s): Butler-O'Hara M, D'Angio CT. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 October-November; 22(7): 541-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12368969

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Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Author(s): Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, Saia OS. Source: European Journal of Pediatrics. 2002 April; 161(4): 202-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12014386

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Safety and efficacy of ibuprofen versus indomethacin in preterm infants. Author(s): Morley GM. Source: European Journal of Pediatrics. 2003 January; 162(1): 62; Author Reply 63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607538

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School-age outcomes of very low birth weight infants in the indomethacin intraventricular hemorrhage prevention trial. Author(s): Vohr BR, Allan WC, Westerveld M, Schneider KC, Katz KH, Makuch RW, Ment LR. Source: Pediatrics. 2003 April; 111(4 Pt 1): E340-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671149

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Severe heart failure due to ductal constriction caused by maternal indomethacin. Author(s): Mushiake K, Motoyoshi F, Kinoshita Y, Nakagawa A, Ito M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 April; 44(2): 174-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896878

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Short-lasting primary headaches: focus on trigeminal automatic cephalgias and indomethacin-sensitive headaches. Author(s): Goadsby PJ. Source: Current Opinion in Neurology. 1999 June; 12(3): 273-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10576887

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Should a prolonged or short course of indomethacin be used in preterm infants to treat patent ductus arteriosus? Author(s): Shah S. Source: Archives of Disease in Childhood. 2003 December; 88(12): 1132-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670791

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Similarities between ileal Crohn's disease and indomethacin experimental jejunal ulcers in the rat. Author(s): Anthony A, Pounder RE, Dhillon AP, Wakefield AJ. Source: Alimentary Pharmacology & Therapeutics. 2000 February; 14(2): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10651666

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Simultaneous densitometric determination of indomethacin and its degradation products, 4-chlorobenzoic acid and 5-methoxy-2-methyl-3-indoleacetic acid, in pharmaceutical preparations. Author(s): Krzek J, Starek M. Source: J Aoac Int. 2001 November-December; 84(6): 1703-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11767134

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Spontaneous motility in preterm infants treated with indomethacin. Author(s): Bos AF, Venema IM, Bergervoet M, Zweens MJ, Pratl B, van Eykern LA. Source: Biology of the Neonate. 2000 October; 78(3): 174-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044765

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Square-wave adsorptive cathodic stripping voltammetric determination of antiinflammatory indomethacin drug in tablets and human serum at a mercury electrode. Author(s): El-Hefnawy GB, El-Hallag IS, Ghoneim EM, Ghoneim MM. Source: Analytical and Bioanalytical Chemistry. 2003 May; 376(2): 220-5. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682707

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Stable bony integration with and without short-term indomethacin prophylaxis. A 5year follow-up. Author(s): Trnka HJ, Zenz P, Zembsch A, Easley M, Ritschl P, Salzer M. Source: Archives of Orthopaedic and Trauma Surgery. 1999; 119(7-8): 456-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10613239

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Strictly unilateral headache reminiscent of hemicrania continua resistant to indomethacin but responsive to gabapentin. Author(s): Mariano Da Silva H, Alcantara MC, Bordini CA, Speciali JG. Source: Cephalalgia : an International Journal of Headache. 2002 June; 22(5): 409-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12110117

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Structure-activity relationship of indomethacin analogues for MRP-1, COX-1 and COX-2 inhibition. identification of novel chemotherapeutic drug resistance modulators. Author(s): Touhey S, O'Connor R, Plunkett S, Maguire A, Clynes M. Source: European Journal of Cancer (Oxford, England : 1990). 2002 August; 38(12): 166170. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12142058

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Study of the solid-phase extraction of diclofenac sodium, indomethacin and phenylbutazone for their analysis in human urine by liquid chromatography. Author(s): Bakkali A, Corta E, Berrueta LA, Gallo B, Vicente F. Source: J Chromatogr B Biomed Sci Appl. 1999 June 11; 729(1-2): 139-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410936

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Surgical excision of heterotopic bone after hip surgery followed by oral indomethacin application: is there a clinical benefit for the patient? Author(s): Wick M, Muller EJ, Hahn MP, Muhr G. Source: Archives of Orthopaedic and Trauma Surgery. 1999; 119(3-4): 151-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10392508

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Synergistic effect of indomethacin with adriamycin and cisplatin on tumor growth. Author(s): Hattori K, Matsushita R, Kimura K, Abe Y, Nakashima E. Source: Biological & Pharmaceutical Bulletin. 2001 October; 24(10): 1214-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11642337

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Synthesis of indomethacin analogues for evaluation as modulators of MRP activity. Author(s): Maguire AR, Plunkett SJ, Papot S, Clynes M, O'Connor R, Touhey S. Source: Bioorganic & Medicinal Chemistry. 2001 March; 9(3): 745-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11310610

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The controversy surrounding indomethacin for tocolysis. Author(s): Macones GA, Marder SJ, Clothier B, Stamilio DM. Source: American Journal of Obstetrics and Gynecology. 2001 February; 184(3): 264-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228471

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The effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate. Author(s): Suarez VR, Thompson LL, Jain V, Olson GL, Hankins GD, Belfort MA, Saade GR. Source: American Journal of Obstetrics and Gynecology. 2002 October; 187(4): 886-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12388970

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The effect of indomethacin on hepatitis B virus replication in chronic healthy carriers. Author(s): Kapicioglu S, Sari M, Kaynar K, Baki A, Ozoran Y. Source: Scandinavian Journal of Gastroenterology. 2000 September; 35(9): 957-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11063156

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The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial. Author(s): Panter KR, Hannah ME, Amankwah KS, Ohlsson A, Jefferies AL, Farine D. Source: British Journal of Obstetrics and Gynaecology. 1999 May; 106(5): 467-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430197

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The effect of sofalcone on indomethacin-induced gastric ulcers in a Helicobacter pylori-infected gnotobiotic murine model. Author(s): Kabir AM, Shimizu K, Aiba Y, Igarashi M, Takagi A, Koga Y. Source: Alimentary Pharmacology & Therapeutics. 2000 April; 14 Suppl 1: 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807428

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The effects of indomethacin on intracranial pressure and cerebral haemodynamics in patients undergoing craniotomy: a randomised prospective study. Author(s): Rasmussen M, Tankisi A, Cold GE. Source: Anaesthesia. 2004 March; 59(3): 229-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984519

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The effects of meloxicam, indomethacin or NS-398 on eicosanoid synthesis by fresh human gastric mucosa. Author(s): Tavares IA. Source: Alimentary Pharmacology & Therapeutics. 2000 June; 14(6): 795-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10848664

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The effects of smoking and indomethacin on small intestinal permeability. Author(s): Suenaert P, Bulteel V, Den Hond E, Hiele M, Peeters M, Monsuur F, Ghoos Y, Rutgeerts P. Source: Alimentary Pharmacology & Therapeutics. 2000 June; 14(6): 819-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10848667

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The influence of indomethacin on the metabolism and cytokine secretion of human aneurysmal aorta. Author(s): Franklin IJ, Walton LJ, Greenhalgh RM, Powell JT. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 1999 July; 18(1): 35-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10388637

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The marked anticancer effect of combined VCR, MTX, and indomethacin against drug-resistant recurrent small cell lung carcinoma after conventional chemotherapy: report of a case. Author(s): Kobayashi S, Okada S, Hasumi T, Sato N, Fujimura S. Source: Surgery Today. 1999; 29(7): 666-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452250

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The modulation of androgen metabolism by estradiol, minocycline, and indomethacin in a cell culture model. Author(s): Tilakaratne A, Soory M. Source: J Periodontol. 2002 June; 73(6): 585-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083529

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The nonsteroidal anti-inflammatory drugs aspirin and indomethacin attenuate betacatenin/TCF-4 signaling. Author(s): Dihlmann S, Siermann A, von Knebel Doeberitz M. Source: Oncogene. 2001 February 1; 20(5): 645-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11313997

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The role of mitogen-activated protein kinases and their relationship with NF-kappaB and PPARgamma in indomethacin-Induced apoptosis of colon cancer cells. Author(s): Kim TI, Jin SH, Kang EH, Shin SK, Choi KY, Kim WH. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485869

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The use of indomethacin for the prevention of intraventricular brain hemorrhage in high-risk neonates. Author(s): Al-Shawaf EM, Al-Alaiyan SA, Aqeel AY, Gamal MH. Source: Saudi Med J. 2000 March; 21(3): 274-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11533797

•

Thiazole analogues of the NSAID indomethacin as selective COX-2 inhibitors. Author(s): Woods KW, McCroskey RW, Michaelides MR, Wada CK, Hulkower KI, Bell RL. Source: Bioorganic & Medicinal Chemistry Letters. 2001 May 21; 11(10): 1325-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11392547

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Tolerance to early human milk feeding is not compromised by indomethacin in preterm infants with persistent ductus arteriosus. Author(s): Bellander M, Ley D, Polberger S, Hellstrom-Westas L. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 September; 92(9): 1074-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599073

•

Topical 0.1% indomethacin solution versus topical 0.1% dexamethasone solution in the prevention of inflammation after cataract surgery. The Study Group. Author(s): Missotten L, Richard C, Trinquand C. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2001 January-February; 215(1): 4350. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11125269

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Transcriptional induction of Nur77 by indomethacin that results in apoptosis of colon cancer cells. Author(s): Kang HJ, Song MJ, Choung SY, Kim SJ, Le MO. Source: Biological & Pharmaceutical Bulletin. 2000 July; 23(7): 815-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10919358

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Treating extremely low birthweight infants with prophylactic indomethacin. Evidence for short term benefits only. Author(s): McGuire W, Fowlie PW. Source: Bmj (Clinical Research Ed.). 2002 January 12; 324(7329): 60-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786435

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•

Tricuspid regurgitation in a pair of twins at birth secondary to antenatal indomethacin. Author(s): Kumar R, Sharma YP, Gupta I. Source: Indian Pediatrics. 2001 October; 38(10): 1185-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11677312

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Tubulointerstitial nephritis with anti-neutrophil cytoplasmic antibody following indomethacin treatment. Author(s): Sakai N, Wada T, Shimizu M, Segawa C, Furuichi K, Kobayashi K, Yokoyama H. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 November; 14(11): 2774. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534532

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Tympanic displacement analysis in healthy volunteers after indomethacin administration. Author(s): Walsted A, Wagner N, Andersen KM. Source: Acta Oto-Laryngologica. 2002 December; 122(8): 822-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12542199

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Uncommon adverse maternal effects with indomethacin for tocolysis. Author(s): Lissak A, Fruchter O, Abramovici H. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 December; 67(3): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10659904

•

UV erythema reducing capacity of mizolastine compared to acetylsalicylic acid or both combined in comparison to indomethacin. Author(s): Grundmann JU, Bockelmann R, Bonnekoh B, Gollnick HP. Source: Photochemistry and Photobiology. 2001 October; 74(4): 587-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11683039

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CHAPTER 2. NUTRITION AND INDOMETHACIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and indomethacin.

Finding Nutrition Studies on Indomethacin 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 “indomethacin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “indomethacin” (or a synonym): •

A comparative study of the antipyretic effects of indomethacin and dipyrone in rats. Author(s): Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de Sao Paulo, Ribeirao Preto, Brazil. [email protected] Source: De Souza, G E P Cardoso, R A Melo, M C C Fabricio, A S C Silva, V M S Lora, M De Brum Fernandes, A J Rae, G A Ferreira, S H Zampronio, A R Inflamm-Res. 2002 January; 51(1): 24-32 1023-3830

•

Chitosan microspheres prepared by an aqueous process: release of indomethacin. Author(s): Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147 002, India. Source: Aggarwal, A Kaur, S Tiwary, A K Gupta, S J-Microencapsul. 2001 NovDecember; 18(6): 819-23 0265-2048

•

Chronic administration of indomethacin increases role of nitric oxide in hypercapnic cerebrovasodilation in piglets. Author(s): University of Texas Health Science Center, San Antonio, USA. [email protected] Source: Son, Minnette Zuckerman, Samuel Prostaglandins-Other-Lipid-Mediat. 2002 January; 67(1): 1-11 1098-8823

•

Indomethacin attenuates post-suspension hypotension in Sprague-Dawley rats. Author(s): Depts. of Pharmacology/Toxicology, Morehouse School of Medicine, Atlanta, Georgia, USA. [email protected] Source: Bayorh, M A Eatman, D Wang, M Socci, R R Emmett, N Thierry Palmer, M JGravit-Physiol. 2001 December; 8(2): 77-83 1077-9248

•

Indomethacin, caffeine and prochlorperazine alone and combined revert hyperalgesia in in vivo models of migraine. Author(s): Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy. Source: Galeotti, N Ghelardini, C Grazioli, I Uslenghi, C Pharmacol-Res. 2002 September; 46(3): 245-50 1043-6618

•

Inhibitory actions of indomethacin on electrical and mechanical responses produced by nerve stimulation in circular smooth muscle of the guinea-pig gastric fundus. Author(s): Department of Physiology, Nagoya City University Medical School, Nagoya, Japan. Source: Yoneda, S Kito, Y Suzuki, H J-Smooth-Muscle-Res. 2001 August; 37(3-4): 81-93 0916-8737

•

The effect of nimesulide on the indomethacin- and ethanol-induced gastric ulcer in rats. Author(s): Department of Pharmacology, Ataturk University, Medical Faculty, Erzurum, Turkey. [email protected] Source: Suleyman, Halis Akcay, Fatih Altinkaynak, Konca Pharmacol-Res. 2002 February; 45(2): 155-8 1043-6618

•

The protective action of melatonin on indomethacin-induced gastric and testicular oxidative stress in rats. Author(s): Zoology Department, Faculty of Science, University of Mansoura, Egypt. Source: Othman, A I El Missiry, M A Amer, M A Redox-Repage 2001; 6(3): 173-7 13510002

Nutrition

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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

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

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/

•

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/

•

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

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMD®Health: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to indomethacin; 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 Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com

•

Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com

•

Food and Diet Garlic Alternative names: Allium sativum Source: Integrative Medicine Communications; www.drkoop.com

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CHAPTER 3. DISSERTATIONS ON INDOMETHACIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to indomethacin. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “indomethacin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on indomethacin, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Indomethacin ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to indomethacin. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Exercise Training, Indomethacin, and Isoproterenol-Induced Myocardial Necrosis (Infarction, Prostaglandin, 6-Keto-PGF (1-alpha), Prostacyclin, Creatine Kinase) by Brodowicz, Gary Ray, PhD from The Ohio State University, 1986, 134 pages http://wwwlib.umi.com/dissertations/fullcit/8618752

•

The Role of Inflammation in Delayed Muscle Soreness (DMS) and the Effects of Indomethacin on DMS and Perceived Exertion (Exercise) by Smith, Lucille Lakier, PhD from Virginia Polytechnic Institute and State University, 1986, 246 pages http://wwwlib.umi.com/dissertations/fullcit/8620667

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Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 4. CLINICAL TRIALS AND INDOMETHACIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning indomethacin.

Recent Trials on Indomethacin The following is a list of recent trials dedicated to indomethacin.8 Further information on a trial is available at the Web site indicated. •

Fluorouracil, Phenylbutyrate, Indomethacin, and Interferon Gamma in Treating Patients With Advanced Colorectal Cancer Condition(s): stage IV colon cancer; Stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum Study Status: This study is currently recruiting patients. Sponsor(s): Mount Sinai Medical Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon-gamma may interfere with the growth of tumor cells and slow the growth of the tumor. Combining more than one drug with interferon-gamma may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining fluorouracil with phenylbutyrate, indomethacin, and interferon-gamma in treating patients who have stage IV colorectal cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002796

8

These are listed at www.ClinicalTrials.gov.

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•

Indomethacin

Randomized Indomethacin GMH/IVH Prevention Trial Condition(s): intraventricular hemorrhage (IVH); bleeding in the brain; prematurity; very low birth weight infants Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this multicenter trial is to determine if indomethacin prevents bleeding in the brain of very low birth weight preterm infants. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033917

•

Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP) Condition(s): Infant, very low birth weight; Infant, premature; Ductus Arteriosus, Patent Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD); Medical Research Council of Canada Purpose - Excerpt: This trial will determine whether giving low-dose indomethacin to infants weight 500 to 999 grams (approximately 1 to 2 pounds) at birth improves their survival without cerebral palsy or developmental problems at 18 to 22 months of age. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009646

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 “indomethacin” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON INDOMETHACIN 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 “indomethacin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on indomethacin, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Indomethacin By performing a patent search focusing on indomethacin, 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 indomethacin: •

Article useful for administration of transdermally, orally or by means of implant

pharmacologically-active

substances

Inventor(s): Berner; Bret (Ardsley on Hudson, NY), Kydonieus; Agis (Kendall Park, NJ), Shah; Kishore R. (Bridgewater, NJ) Assignee(s): Hercon Laboratories Corporation (new York, Ny) Patent Number: 5,468,501 Date filed: February 8, 1995 Abstract: A device useful for administration of pharmacologically-active substances transdermally, orally, or by means of subdermal implant includes an impermeable backing layer, a plasticized polyvinyl chloride layer, and an adhesive layer, wherein the plasticized polyvinyl chloride layer includes from about 20 up to about 70% by weight of a polyvinyl chloride resin, from about 20 up to about 70% by weight of a plasticizer, and from about 0.5 up to about 35% by weight of a pharmacologically-active substance such as isosorbide dinitrate, nicotine, clonidine, guanfacine, indomethacin, nitroglycerin, and prostaglandin and optionally excipients. Excerpt(s): This invention relates broadly to articles of manufacture for administration of pharmacologically-active substances, transdermally, orally and by means of implant (e.g., subdermal implant). The devices consist essentially of a vinyl chloride polymer or copolymer of vinyl chloride containing a majority of vinyl chloride monomeric units and a small amount of other vinyl monomeric units, e.g., vinyl acetate, and intimately dispersed therewith at least one of said pharmacologically-active agents and a plasticizer. Examples of pharmacologically-active agents are isosorbide dinitrate, nicotine, indomethacin, clonidine, glyceryl trinitrate, guanfacine and prostaglandin. Contemplated within the scope of this invention are devices for the controlled release and transdermal administration of such pharmacologically-active agents as nitroglycerine (e.g., in the treatment of conditions, e.g., angina pectoris). Many prior art articles of manufacture have been disclosed for controlled release delivery of various drugs including transdermal delivery of nitroglycerin. In general, however, available commercial devices and indeed devices published in the prior art are limited with respect to rate of delivery of pharmacologically-active substance. Canadian Patent No. 930,668 discloses a bandage for administering drugs comprised of a backing member, a pressure sensitive adhesive, and at least one reservoir disposed between the backing member and pressure sensitive adhesive. The reservoir is comprised of a systemically active drug formulation confined within a wall member, the wall member being formed from a drug release rate controlling material. The reservoir can be in the form of discrete microcapsules or distinct reservoir compartments or layers. The reservoir can also be in the form of walled containers having one or more interior drug-containing chambers, as well as solid matrices having a systemically active drug distributed therethrough. The Canadian patent discloses a wide variety of materials which can be used to form the reservoir. Among the materials mentioned are silicone rubbers, hydrophilic polymers of monoesters of an olefinic acid, polyvinylalcohol, polyvinylacetate, plasticized polyvinylchloride, plasticized nylon, collagen, modified collagen, gelatin, and waxes such as polyethylene wax, oxidized polyethylene wax, hydrogenated castor oil and the like, with the silicone rubbers being preferred. The Canadian patent does not contain any examples showing the use of plasticized polyvinyl chloride.

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Web site: http://www.delphion.com/details?pn=US05468501__ •

Combinations of tumor necrosis factors and anti-inflammatory agents and methods for treating malignant and non-malignant diseases Inventor(s): Fiers; Walter C. (Destelbergen, BE), Goldberg; Alfred L. (Brookline, MA), Kettelhut; Isis C. (Brookline, MA) Assignee(s): Biogen, Inc. (cambridge, Ma), President and Fellows of Harvard College (cambridge, Ma) Patent Number: 4,980,160 Date filed: June 29, 1989 Abstract: This invention relates to combinations and methods for the treatment of malignant and non-malignant diseases. More particularly, this invention relates to combinations of natural or recombinant tumor necrosis factors ("TNF") and nonsteroidal anti-inflammatory agents, such as indomethacin and ibuprofen, useful for the growth inhibition or killing of transformed cells. According to this invention, the nonsteroidal anti-inflammatory agents are used to reduce or eliminate the toxic side effects of high doses of TNFs employed in the treatment of malignant and non-malignant neoplastic diseases. Advantageously, the combinations and methods of this invention allow the administration of higher doses of TNF than those tolerated in conventional treatment regimens based upon TNF alone. Excerpt(s): Malignant diseases are a group of diseases characterized by tumorigenic or neoplastic cell growth. Such diseases include malignant hematological systemic diseases, carcinomas, sarcomas, myelomas, melanomas, lymphomas and papillomas. Non-malignant neoplastic diseases, including non-malignant tumors, are also characterized by neoplastic cell growth which is localized to a specific area. The transformation of normal cells within the body into either malignant or non-malignant neoplasms may be induced by chemical carcinogens, radiation, physical agents or spontaneous tumorigenic growth. The precise etiology of many malignant and nonmalignant diseases remains unknown. Accordingly, treatments for these diseases are limited, and effective agents are not always conventionally available for a specific disease. Such diseases have been treated, for example, by surgical techniques or by nonsurgical methods including chemotherapy, radiation and immunotherapy. Any value of such treatment techniques, however, is often diminished by adverse side effects or risks attendant with their use. For example, non-surgical techniques such as chemotherapy generally have immunosuppressant effects and may increase the patient's susceptibility to secondary infections. Surgical treatments to excise malignant or non-malignant tumors involve risks which accompany any invasive procedure and may not effectively remove or eliminate the entire transformed cell population. Moreover, certain malignant diseases are resistant to conventional treatment techniques. For example, most skin melanomas are considered to be radio-resistant. No single agent or combination chemotherapy has been successful in effecting consistent regressions of malignant melanomas. Malignant renal cell carcinoma is also resistant to available single agent and combination chemotherapies. Web site: http://www.delphion.com/details?pn=US04980160__

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Complex of tea-leaf extract and active aluminum hydroxide Inventor(s): Asai; Hajime (Nagoya, JP), Hara; Yukihiko (Shizuoka, JP), Kitamikado; Tadashi (Inuyama, JP), Nakamura; Kozo (Tokyo, JP), Okushio; Kazuo (Shizuoka, JP), Yamamoto; Hajimu (Nagoya, JP) Assignee(s): Mitsui Norin Co., Ltd. (tokyo, Jp) Patent Number: 4,913,909 Date filed: October 2, 1986 Abstract: Extract of tea leaves or (-)-epigallocatechin gallate as the principal ingredient of the extract forms a complex with active aluminum hydroxide. The animal test using rats has established that these complexes have therapeutic effect for gastric ulcers, e.g. pylorus-ligated ulcer and indomethacin-induced ulcer, when orally administered. Tests were also undertaken for the effect on the secretion of gastric juice and acute toxicity of these complexes using rats and mice as the test animals. Excerpt(s): The present invention relates to a complex of tea-leaf extract, of which the principal ingredient is (-)-epigallocatechin gallate, referred to as EGCg hereinbelow, and active aluminum hydroxide or a complex of the EGCg per se and active aluminum hydroxide. The complex of the present invention has excellent antiulcer activity, antipeptic activity and antacid activity so that it is useful as a therapeutic medicine for digestive ulcers. The complex of the present invention is a novel material not known in the prior art. The inventors have previously undertaken extensive investigations on an industrial method for the preparation of tealeaf extract containing EGCg as the principal ingredient, which is one of the starting materials for the preparation of the inventive complex, and the results are disclosed in Japanese Patent Kokai No. 59-219384 (See also U.S. Pat. No. 4,673,530). They further have continued investigations on a method for the fractionation of catechin compounds from the tea-leaf extract and the results are disclosed in Japanese Patent Kokai No. 60-13780 (See also U.S. Pat. No. 4,613,672). Web site: http://www.delphion.com/details?pn=US04913909__

•

Composition comprising indomethacin [non-steroidal anti-inflammatory agent] and effectively non-antibacterial tetracycline to reduce bone loss Inventor(s): Golub; Lorne M. (Smithtown, NY), Greenwald; Robert A. (Melville, NY), McNamara; Thomas F. (Port Jefferson, NY), Ramamurthy; Nangavarum S. (Smithtown, NY) Assignee(s): The Research Foundation of State University of New York (albany, Ny) Patent Number: 5,459,135 Date filed: February 23, 1994 Abstract: A method for treating mammals suffering from rheumatoid arthritis and other tissue-destructive (chronic inflammatory or other) conditions associated with excess metalloproteinase activity comprising administering to the mammal an amount of a tetracycline that is effectively anti-metalloproteinase, but that is not effectively antimicrobial, and an amount of non-steroidal anti-inflammatory agent which, when combined with the effectively anti-metalloproteinase amount of tetracycline, results in a significant reduction of tissue destruction and/or bone loss. Excerpt(s): The present invention relates to an anti-collagenolytic composition useful in the treatment of rheumatoid arthritis and other tissue-destructive conditions associated

Patents 85

with excess collagenolytic activity as well as a method for using such formulations. Tetracycline as well as the 5-OH (terramycin) and 7-Cl (Aureomycin) derivatives exist in nature, and are well known antibiotics. Natural tetracyclines may be modified without losing their antibiotic properties, although certain elements of the structure must be retained. The modifications that may and may not be made to the basic tetracycline structure have been reviewed by Mitscher in The Chemistry of Tetracyclines, Chapter 6. According to Mitscher, the substituents at positions 5-9 of the tetracycline ring system may be modified without the complete loss of antibiotic properties. Changes to the basic ring system or replacement of the substituents at positions 1-4 and 10-12, however, generally lead to synthetic tetracyclines with substantially less or effectively no antibacterial activity. For example, 4-dedimethylaminotetracycline is commonly considered to be a non-antibacterial tetracycline. The use of tetracycline antibiotics, while effective, may lead to undesirable side effects. For example, the long term administration of antibiotic tetracyclines may reduce or eliminate healthy flora, such as intestinal flora, and may lead to the production of antibiotic resistant organisms or the overgrowth of yeast and fungi. Web site: http://www.delphion.com/details?pn=US05459135__ •

Compound compositions with improved analgesic antipyretic and anti-inflammatory activity Inventor(s): Di Schiena; Michele G. (Cisliano, IT), Paster; Zvi (Givataim, IL) Assignee(s): Life Science Research Israel Ltd (ness Ziona, Il), Ricerfarma S.r.l. (milan, It) Patent Number: 4,859,658 Date filed: February 29, 1988 Abstract: Pharmaceutical compositions containing thioacetamol and an amount of a non-steroidal anti-inflammatory drug selected from aspirin, indomethacin, dichlofenac, naproxen, sulindac and fenbufen potentiate the activity of these drugs and reduce their undesiderable side-effects. Excerpt(s): This invention is directed to improved compositions useful as analgesic, antipyretic or anti-inflammatory agents either in human or veterinary therapy. Thiocetamol, p-acetamidophenyl thiophene-2-carboxylate, is a known compound described in GB-ANo. 1585047 (Anphar S. A.). It is therapeutically useful as an analgesic and anti-pyretic agent in treatment of the common cold or influenza. Moreover, its acute median lethal dose (LD.sub.50) is far lower than that of the parent paracetamol because of its remarkable lower toxicity towards the hepatic parenchyma. Aspirin, indomethacin, diclofenac, naproxen, sulindac and fenbufen (henceforward designated FANS) are, on the other hand, all well known compounds, therapeutically useful as analgesic, antipyretic and anti-inflammatory non-steroidal drugs. Unfortunately, however, these drugs may all cause a variety of undesirable side effects including in some cases, especially when aspirin or indomethacin is administered, a painless bleeding from the gastrointestinal tract. Web site: http://www.delphion.com/details?pn=US04859658__

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Controlled release indomethacin Inventor(s): Mehta; Atul M. (Ramsey, NJ) Assignee(s): Norjec Development Associates, Inc. (ramsey, Ny) Patent Number: 4,938,968 Date filed: July 26, 1988 Abstract: In accordance with the present invention, the controlled release formulation contains coated pellets of indomethacin of only one type. The pellet releases indomethacin in both immediate and sustained release form. The immediate release indomethacin is rapidly absorbed from the stomach to provide a bolus dose of active agent. The sustained release indomethacin is gradually released over time to maintain the blood levels at effective concentrations for long periods of time. Excerpt(s): This invention relates to a novel oral pharmaceutical formulation of indomethacin having controlled release properties. The formulation is directed to a coated pellet from which a pharmaceutical compound is slowly released over time. This formulation has been shown to exhibit excellent controlled release properties. The formulation provides an immediate release indomethacin for elevating blood levels to pharmacologically effective levels and sustained release indomethacin for maintaining those levels. It has long been known that almost all pharmacologically active compounds are most effective when present in plasma within a certain concentration range. Above this range, there sometimes may be a danger that deleterious side effects may become manifest and even when there is not the danger, excess drug in the blood plasma may be wasted if the concentration is significantly above the blood level that results in the maximum pharmacological effect. Below this range, there often may be a danger that the active agent may not be maximally effective or even effective at all. Web site: http://www.delphion.com/details?pn=US04938968__

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Divalent metal complexes of indomethacin, compositions and medical methods of use thereof Inventor(s): Biffin; John R. (New South Wales, AU), Regtop; Hubertus L. (New South Wales, AU) Assignee(s): Biochemical Veterinary Research Pty. Ltd. (au) Patent Number: 5,466,824 Date filed: March 24, 1994 Abstract: The present invention provides a process for the preparation of a complex of indomethacin and a divalent metal comprising forming a solution by dissolving indomethacin and a salt of said divalent metal in a tertiary amide or cyclic tertiary amide, adding a C.sub.1-4 alkanol or C.sub.3-6 ketone to the solution to precipitate the complex, and separating the precipitated complex from the solution. The present invention also provides a method for the treatment of inflammation or pain in a mammal requiring such treatment, comprising administering to said mammal an antiinflammatory or analgesically effective amount of a complex of indomethacin and a divalent metal, the complex having the formula [M].sub.2 [indomethacin].sub.4 [S].sub.n, wherein M is the divalent metal, S is a molecule of a tertiary amide or a cyclic tertiary amide, and n is 2 or 3, or of a pharmaceutical composition comprising said complex together with a pharmaceutically acceptable carrier, diluent and/or excipient.

Patents 87

The present invention further provides a complex of indomethacin and a divalent metal, the complex having the formula [M].sub.2 [indomethacin].sub.4 [S].sub.n, wherein M, S, and n are defined above, and a pharmaceutical composition comprising this complex together with a pharmaceutically acceptable carrier, diluent and/or excipient. Excerpt(s): The present invention relates to a process for the preparation of complexes of indomethacin and divalent metals, and more particularly to an efficient process for the preparation of copper-indomethacin complexes. The invention also relates to a composition containing a complex of indomethacin and a divalent metal and more particularly to an oral composition containing copper-indomethacin complexes. The invention further relates to a method for the treatment of various conditions in mammals and in particular to shin soreness and other musculo-skeletal inflammation in mammals, including man, and more particularly to the treatment of those conditions in horses. Web site: http://www.delphion.com/details?pn=US05466824__ •

Enhancement of benzalkonium chloride preservative activity in formulations containing an incompatible drug Inventor(s): Lucero; Jasmin C. (Irvine, CA) Assignee(s): Allergan, Inc. (irvine, Ca) Patent Number: 5,504,113 Date filed: March 2, 1994 Abstract: A formulation and method includes an acceptable drug, such as Prostaglandins, Flurbiprofen, Keterolac Tromethamine, Cetirizine HCl Indomethacin and Bufrolin, which are interactive with benzalkonium chloride to form a precipitate along with benzalkonium chloride acting as a preservative and an amino acid having enough positive charge at the pH of the formulation and/or Tromethamine present in an amount sufficient to interfere with the interaction between the drug and benzalkonium chloride in order to maintain the preservative activity of the benzalkonium chloride. Further, the use of Lysine, L-arginine, or Histidine is also useful in reducing the cytotoxicity of the formulation. Excerpt(s): The present invention generally relates to improved formulations and solutions and more particularly to improved preservative systems for acceptable drug formulations which have an incompatibility with benzalkonium chloride (BAK) such as Prostaglandins, Flurbiprofen, Keterolac Tromethamine, Cetirizine HCl and Indomethacin. More specifically, the present invention pertains to the preservative for an ophthalmologically acceptable drug such as Bufrolin having activity for treating seasonal allergies, allergic conjunctivitis, giant papillar conjunctivitis, and vernal keratoconjunctivitis. Ophthalmologically acceptable drug formulations generally contain effective compounds and a number of ophthalmologically acceptable excipients. formulations generally include solutions, ointments, and suspensions, etc. The formulations may include excipients such as stabilizing agents, surfactants, buffering systems, chelating systems, viscosity agents, tonicity agents, and, importantly, a preservative. Ophthalmic formulations, understandably, must be sterile and if a multidose regimen is intended, the formulation must be preserved with an effective antimicrobial agent. Web site: http://www.delphion.com/details?pn=US05504113__

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Gelatin or collagen hydrolysate containing drug formulation that provides for immediate release of nanoparticle drug compounds Inventor(s): Freidenreich; Jurgen (Schriesheim, DE), Schick; Ursula (Schriesheim, DE), Werry; Jurgen (Ludwigshafen, DE), Wunderlich; Jens-Christian (Heidelberg, DE) Assignee(s): Alfatec Pharma Gmbh (heidelberg, De) Patent Number: 5,932,245 Date filed: October 25, 1994 Abstract: Nanosols and process for preparing the same allow colloidally dispersed solutions of scarcely water-soluble active substances to be stabilized with gelatin or its derivatives, by partly or fully setting the iso-ionic point (IIP, equivalent to a neutral charge) between the gelatin and the surface charged active substance particles. In order to neutralize the charge of the system composed of active substance particles and gelatin, the surface charge of the particles is compensated by a corresponding opposite charge of the gelatin molecules. For that purpose, a determined charge in relation to the isoelectric point (IEP) and the pH value of the solution is set on the gelatin molecules. By stabilizing in this way the practically monodispersed state thus generated, the Ostwald maturation of the colloidal particles of scarcely soluble active substance is strongly reduced. A new form of pharmaceutical administration having new properties can thus be obtained with generally scarcely water-soluble inorganic and organic compounds, in particular medicaments with a problematic bioavailablity. Preferred medicaments are glibenclamide and 3-indolylacetic acid derivatives, such as indomethacin or acemetacin. Excerpt(s): The present invention relates to a process for the preparation of a colloidally disperse system of poorly water-soluble pharmaceutical substances or of poorly watersoluble inorganic and/or organic compounds. It furthermore relates to a pharmaceutically administrable nanosol, i.e. a stable colloidally disperse system of poorly water-soluble pharmaceutical substances with gelatin. It furthermore relates to an immediate-effect medicament for the treatment of rheumatic and/or inflammatory diseases, which contains a 3-indolylacetic acid derivative. It finally relates to an immediate-effect medicament for the treatment of diabetes, which contains glibenclamide. c.sub.t : concentration of the substance concerned in solution at time t. This equation gives a mathematical expression for the rate of solution of substances generally (in this case pharmaceutical substances). In this equation the changeable target quantities for the pharmacist are only the saturation concentration (saturation solubility) of the pharmaceutical substance and the substance surface area which can effectively be attacked by the solvent. An increase in these two parameters should also result in an increase in the rate of solution. Web site: http://www.delphion.com/details?pn=US05932245__

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Indomethacin injections and their production method Inventor(s): Hasegawa; Masatoshi (Takatsuki, JP), Matsuda; Shu (Ibaraki, JP), Takenaka; Hiroshi (Kyoto, JP) Assignee(s): Sumitomo Pharmaceuticals Company, Limited (osaka, Jp) Patent Number: 4,990,530 Date filed: August 2, 1989

Patents 89

Abstract: Injections containing anhydrous sodium indomethacin and methods for producing injections containing an hydrous sodium indomethacin which comprise converting a solution of indomethacin to a solution of sodium indomethacin by adding dropwise an aqueous solution of a carbonate of sodium, followed by freeze-drying and heating.The injections of the present invention are practically useful indomethacin injections in which sodium indomethacin anhydride has high safety and chemically high purity and stability, and the lyophilized pharmaceutical preparations are excellent also in that redissolution thereof is facilitated. By the methods for the production of the present invention, it is possible to produce said anhydrous sodium indomethacin efficiently. Excerpt(s): This invention relates to practically useful injections of indomethacin and the methods for the production thereof. The injections of the present invention are useful for the therapy, prophylaxis or the like of, for example, acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC). Indomethacin is a medicament which has heretofore been widely used as an antiinflammatory, antipyretic and analgesic in the clinical field, and also, the use thereof as a therapeutic agent for cancers has been attempted. In recent years, much attention has been paid to the use of it for the treatment of AIDS and ARC. Recently, it has come to be suggested that indomethacin which is a cyclo-oxygenase-inhibitor and prostaglandin-synthesisinhibitor can be used as a therapeutic agent for patients of AIDS and ARC, from an in vitro assessment with the use of lymphocytes of patients of AIDS and ARC [F. H. Valone et al, J. Clin. Immunol., 4, 383-387 (1984) and M. M. Reddy et al, Internal. J. Immunopharmacol., 7, 917-921 (1985)]. Furthermore, in vivo application or clinical application has been attempted. It has been shown that when indomethacin is orally administered to patients of AIDS or ARC, fever, languidness, anorexia and other clinical symptoms disappear or are improved, their body weight increase as well, and furthermore patients complicated by esophagus candidiasis can be cured of candidiasis without antifungal therapy [J. Ramirez et al, Lancet, Sep. 6, 570 (1986) and M. H. Grieco et al, Internal. J. Immunother., 11, 295-300 (1986)]. Among those patients, as far as those who retain immune function to some extent are concerned, their immune function can be recovered by oral administration of indomethacin. There is an invention in which the effectiveness on HIV of some prostaglandin-synthesis-inhibitors and cyclo-oxygenaseinhibitors have been confirmed based on in vitro evaluation, and these inhibitors have been made use of as treatment agents for AIDS (EP-A-237796). However, in this invention, it is not clear how effects on AIDS differ depending on the species of medicaments of the prostaglandin-synthesis-inhibitors, and the relationship between in vivo evaluation and clinical effects is not made clear. Web site: http://www.delphion.com/details?pn=US04990530__ •

Medicaments Inventor(s): Bunce; Keith T. (Luton, GB2), Humphrey; Patrick P. A. (Bedford, GB2) Assignee(s): Glaxo Group Limited (london, Gb2) Patent Number: 4,983,621 Date filed: July 6, 1989 Abstract: The invention relates to the co-administration in human or veterinary medicine of 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4Hcarba zol-4-one or a physiologically acceptable salt or solvate thereof and a cyclooxygenase inhibitor such as indomethacin or piroxicam.The two active ingredients,

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which may be administered separately either simultaneously or sequentially, or may be combined in a single pharmaceutical preparation, are useful in the relief and/or prevention of nausea and vomiting. Excerpt(s): This invention relates to improvements in the treatment of gastrointestinal disorders. More particularly it relates to the use of a compound having antagonist activity at 5HT.sub.3 receptors in conjunction with a cyclo-oxygenase inhibitor in the treatment of emesis, and to pharmaceutical compositions containing the two compounds. In the aforementioned specification the compounds are described as potent and selective antagonists of 5-hydroxytryptamine (5HT) at `neuronal` 5HT receptors of the type located on terminals of primary afferent nerves, and which are also present in the central nervous system. Receptors of this type are now designated 5HT.sub.3 receptors. The compounds are described as being of use in the treatment of a human or animal subject suffereing from a condition caused by a disturbance of neuronal 5HT function, for example in the treatment of migraine pain or a psychotic disorder such as schizophrenia. The compounds may also be useful in the treatment of conditions such as anxiety, obesity and mania. We have found, as described in our published European Patent Specification No. 226266, that the compounds disclosed in UK Patent Specification No. 2153821A additionally promote gastric emptying, and are thus useful in the treatment of conditions which may be relieved by the promotion of gastric emptying. Such conditions include gastric stasis and symptoms of gastrointestinal dysfunction such as dyspepsia, reflux oesophagitis, peptic ulcer and flatulence. Web site: http://www.delphion.com/details?pn=US04983621__ •

Method and composition for determining the immunological activity of bioactive substances Inventor(s): Blach-Olszewska; Zofia (Wroclaw, PL), Inglot; Anna (Wroclaw, PL) Assignee(s): Torf Establishment (li) Patent Number: 5,543,300 Date filed: April 26, 1994 Abstract: The immunological activity of certain bioactive substances is determined by treating a human peripheral blood leukocyte (PBL) culture or a suspension of BALB/c mice resident peritoneal cells (RPC), with a solution of the substance to be tested in order to induce production of cytokines which then are determined according to standard identification methods; amplification of the results may be achieved by admixing, to the solution to be tested, a non-steroidal anti-inflammatory drug, preferably indomethacin. The method is also useful for determining the immunological response of a human individual to a therapy using a cytokine inducing substance. Excerpt(s): The present invention relates to a method and composition for assaying certain bioactive substances and determining their immunological activity with respect to their ability to induce production of cytokines. Cytokines, such as interferons (IFNs) and tumor necrosis factors-(TNFs), are hormone-like proteins which play an important role in virtually all immunological reactions, as well as in the regulatory process responsible for the maintenance of homeostasis. The production of such cytokines can be induced by certain substances which, on account of their bioactive and immunomodulating activity, are useful in the therapy of immunodeficiencies and related diseases. There is, of course, a substantial need of methods for properly and easily assaying the immunological activity of such bioactive substances. It is the object of

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the present invention to provide such a method. The method according to the present invention allows one to determine whether a tested substance is able to induce production of different cytokines and permits a quick and efficient check of the properties of certain substances, namely their immunological activity, at each stage of production, separation, purification and formulation into final compositions. The present invention provides also a composition and kits suitable for carrying out said method. Web site: http://www.delphion.com/details?pn=US05543300__ •

Method for enhancing healing of corneal endothelial wounds Inventor(s): Joyce; Nancy C. (Sudbury, MA), Jumblatt; Marcia M. (Louisville, KY), Neufeld; Arthur H. (Newton Highlands, MA) Assignee(s): Eye Research Institute of Retina Foundation, Inc. (boston, Ma) Patent Number: 5,051,443 Date filed: April 13, 1989 Abstract: The composition and method of using a non-steroidal antiinflammatory compound, such as indomethacin and/or a growth factor that causes a change in cell function when bound to specific cell surface receptor, such as epidermal growth factor (EGF), to enhance healing and restore function of the corneal endothelium. The compositions can be administered alone, in combination, or in sequence, before or after injury, for example, in an irrigation solution or in combination with a nutritive solution for storage of cornea prior to transplant. Excerpt(s): This invention is generally in the area of ophthalmic compositions and more specifically relates to a method and compositions for enhancing healing of injuries to the corneal endothelium. The corneal endothelium, a single layer of hexagonal cells at the boundary between the fluid-filled anterior chamber and the clear collagenous stroma at the posterior surface of the cornea, is critical for the maintenance of transparency of the tissue. The cell layer is avascular, lacks innervation, and is bathed on its apical face by aqueous humor. In the aging human, the density of corneal endothelial cells gradually decreases and the remaining cells retain their polygonal shape while becoming wider and thinner to maintain a permeability barrier. When a wound or discontinuity occurs in this tissue, the cells bordering the defect become elongated, migratory, and, perhaps, synthesize new extracellular matrix material. Clinically significant dysfunctions of the endothelium, due to cell loss associated with dystrophies or degenerations caused by ocular diseases, drugs, trauma or surgery, are responsible for the majority of corneal transplants. Despite its physiologic importance, the corneal endothelium is an extremely fragile tissue. Since the endothelium is relatively amitotic in the adult human, repair to areas of injury is via migration and spreading of neighboring cells to cover the defect in the monolayer. At low cell densities, these repair mechanisms may be insufficient to restore the endothelium to full physiologic function. If the endothelial barrier and pump functions become compromised, water enters the stroma and disrupts the precise arrangement of collagen fibrils, eventually resulting in visual impairment. Web site: http://www.delphion.com/details?pn=US05051443__

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Method for treating arthritically inflamed body joints, particularly joints having gouty arthritis Inventor(s): Gertner; Sheldon (39 Ridge Dr., Berkeley Heights, NJ 07922) Assignee(s): None Reported Patent Number: 5,061,724 Date filed: July 18, 1989 Abstract: A method of treating inflammations of body joints in humans by topical application of anti-inflammatory agents may be used to treat joints afflicted by arthritic conditions such as gouty arthritis. The steps of the method include dissolving a predetermined quantity of a known anti-inflammatory drug, applying the medium with dissolved anti-inflammatory drug directly onto the skin covering a body joint known to be inflamed and allowing the medium with dissolved anti-inflammatory drug to be absorbed into the skin. Possible non-steroidal, anti-inflammatory drugs which may be used with the method include indomethacin, phenylbutazone and colchicine. Steroidal non-inflammatory drugs may also be used. Excerpt(s): The present invention relates to a method for treating inflammations of body joints in humans, and in particular, joints afflicted by arthritic conditions such as gouty arthritis. The chronic treatment of gout affecting the big toe or other toes requires daily or prophylactic treatment with one or more drugs. These drugs, such as colchicine, allopurinol, probenecid or indomethacin or combinations of these, have numerous side effects that can cause with time considerable toxicity. In addition, they may adversely affect the action of other drugs given to the patient to treat completely different conditions. More importantly, when the drugs are used to affect small areas such as the toes, relatively high doses must be given which produce overall much greater effects on other body tissues than the toes due to the general distribution of the drug when given by the oral route. It would appear more logical, when the object of therapy is to produce a local anti-inflammatory effect, to treat each local site of inflammation with lower doses of the anti-inflammatory drugs than would be given orally. The local concentrations under these conditions, at the joint, would still be considerably higher than giving such anti-inflammatory drugs orally, where the drug is distributed to all the body tissues and thus diluted. This local application should be domethacin and phenylbutazone (nonsteroidal anti-inflammatory agents) as well as colchicine, which works by a different mechanism. Web site: http://www.delphion.com/details?pn=US05061724__

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Method of attenuating physical damage to the spinal cord Inventor(s): Guth; Lloyd (Ford's Colony, VA), Roberts; Eugene (Monrovia, CA) Assignee(s): City of Hope (duarte, Ca), The Center for Innovative Technology (herndon, Va), The College of William and Mary (williamsburg, Va) Patent Number: 5,574,022 Date filed: April 14, 1994 Abstract: A method is disclosed for attenuation of nervous system damage after injury which comprises administering therapeutic amounts of PREG, PREG-S, or esters of PREG or PREG-S together with an enhancer of secretory processes in non-neural cells

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such as a bacterial lipopolysaccharide and a non-steroidal antiinflammatory substance such as indomethacin. Excerpt(s): This invention relates to the attenuation of nervous system damage after injury produced externally or by processes occurring within the organism itself. More particularly, the invention relates to the prevention of sequelae of nervous system injury by the coadministration of steroid hormones or steroid precursors such as pregnenolone, pregnenolone sulfate, and structurally similar organic compounds together with substances such as bacterial lipopolysaccharides (hereinafter referred to by the abbreviation LPS), ImuVert, muramyl dipeptide, and pyran or dextran polymers that stimulate secretion of cytokines by glia, monocytes, macrophages, and Schwann cells and with non-steroidal antiinflammatory substances or drugs (hereinafter referred to by the abbreviation NSAIDs) such as aspirin, indomethacin, ibuprofen, acetaminophen, sodium salicylate, BW755c, diclofenac, naproxen, and BF389 that suppress the inflammatory effects of enhanced activation of the above-mentioned nonneural cells while not diminishing the recovery-promoting effects of the cytokines secreted by them. Externally initiated injuries to the nervous system are exemplified by contusions or compressions produced by direct blows to the head or spinal cord or by injuries to brain or spinal cord as a result of falls or other accidents; by penetrating wounds caused by knife blades, bullets, or other types of foreign objects or by complete severance of the spinal cord caused by such wounds; by X-rays, electromagnetic radiation, or exposure to radioactive fallout; by infections caused by bacteria, protozoa, yeast, fungi, or viruses. Indigenous modes of injury are exemplified by partial or complete occlusions of blood vessels by immune complexes, platelet aggregations, arteriosclerotic plaques, or sickle cell erythrocytes; by aneurysms, strokes, vascular spasms; by deposition of lipofuscin and/or amyloid; by autoimmune processes in allergic reactions, lupus erythematosus, and demyelinating disorders; by variously produced irritative inflammatory processes in endothelial cells of capillaries of blood vessels which result in permeabilization of blood vessels and the consequent edematous swelling in regions of the brain and spinal cord; or by invasive lesions caused by benign or malignant tumors. Both regionally and globally, the whole functional terrain in the nervous system is disturbed after injury occurs. There is damage to microvasculature and there are losses of neuronal cells, decreases in neuronal processes in surviving cells, and increases in various glial elements and/or changes in their proportions and functions. Accelerated degeneration of neural, endothelial, neuroendocrine, and endocrine elements together with incoordination of the networks of relations among the cellular components of the immune system with coincident disruption of neurovascular relations and breakdown of the blood-brain barrier in the affected regions predispose to development of circulating and cellular autoantibodies to various polymeric cellular components of cellular and extracellular components in the disrupted regions. This leads to enhanced cellular destruction and deposition of the relatively indigestible debris of immune complexes in capillaries and extracellular sites. A further consequence of perturbation of the immune system is immunosuppression, with resultant activation of latent viruses destructive to the nervous system. Web site: http://www.delphion.com/details?pn=US05574022__

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Method of inhibiting secretory effects caused by Cholera Inventor(s): Fang; Guodong D. (Charlottesville, VA), Fonteles; Manasses C. (Porangabussu, BR), Guerrant; Richard L. (Charlottesville, VA) Assignee(s): Uva Patent Foundation (charlottesville, Va) Patent Number: 5,929,095 Date filed: June 17, 1997 Abstract: The administration of the PAF antagonists BN 52021 and SR 27417, in combination with cyclooxygenase antagonist indomethacin are disclosed as effective in inhibiting the secretory effects caused by Cholera toxin. Excerpt(s): The invention relates to the treatment of antibiotic associated colitis, typically due to Clostridium difficile using Platelet Activating Factor antagonists, such as WEB 2170, SR 27417 or BN 52021, or the cyclooxygenase antagonists, such as indomethacin. The PAF antagonists BN 52021 and SR 27417 and the cyclooxygenase antagonist indomethacin were effective in inhibiting the secretory effects caused by C. difficle Toxin A and even by Cholera toxin. Clostridium difficile is one of the most frequently recognized bacterial causes of diarrheal disease in hospitalized adults in industrialized countries. The microorganism can be acquired nosocomially and is present in environmental sources. Antibiotic associated colitis and pseudomembranous colitis are frequently associated with cytotoxigenic Clostridium difficile. The frequency of Clostridium difficile toxin associated with antibiotic associated colitis is 50-80% and with pseudomembranous colitis is 90-100%. Despite available treatment for antibiotic associated colitis and pseudomembranous colitis, relapses occur in 20-25% of patients. Vancomycin and metronidazole can be effective, but are subject to relapse after the use of the drugs may occur. Clostridium difficile produces two toxins, A (enterotoxic) and B (cytopathic), the former (Toxin A) being implicated in the pathogenesis of pseudomembranous colitis. Toxin A causes hemorrhagic fluid accumulation associated with mucosal damage and a cytopathic effect in tissue culture cells. In experimental animals such as rabbits, toxin A causes hemorrhagic fluid secretion and cell damage in ligated intestinal segments of loops, and is considered to be the cause of antibioticassociated colitis in experimental hamsters and in people. Web site: http://www.delphion.com/details?pn=US05929095__

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Methods for administration of antilipemic drugs Inventor(s): Kuhrts; Eric H. (Woodside, CA), Morrow; Jason D. (Nashville, TN), Roberts, II; L. Jackson (Nashville, TN) Assignee(s): Lipoprotein Technologies, Inc. (woodside, Ca), Vanderbilt University (nashville, Tn) Patent Number: 5,773,453 Date filed: April 19, 1995 Abstract: The present invention concerns methods for reducing cutaneous flushing in a patient to whom niacin is administered. According to the present method, two or more doses of a nonsteroidal anti-inflammatory drug are administered to a patient prior to administering niacin. Alternatively, the nonstcroidal anti-inflammatory drug can be administered concurrently with niacin administration. The nonstcroidal antiinflammatory drug can be aspirin, ibuprofen, indomethacin, phenylbutazone, or

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naproxen. The nonsteroidal anti-inflammatory drug is administered in an amount effective to reduce cutaneous flushing caused by the niacin, and is administered in an amount up to 160 mg for aspirin and ibuprofen, 10 mg for indomethacin, and 100 mg for phenylbutazone and naproxen. Excerpt(s): The invention concerns methods and compositions for administration of antihyperlipidemic (ie., hypolipemic or antilipemic) drugs, particularly nicotinic acid and its derivatives, while producing decreased flushing reaction. Abnormally high levels of circulating lipids (hyperlipidemias) are a major predisposing factor in development of atherosclerosis. Elevated levels of serum cholesterol and cholesteryl esters, which are carried by the beta-lipoprotein or low density lipoprotein (LDL) and lipoprotein (a) (Lp(a)) fractions of serum lipids, are known to be atherogenic. Also implicated in cardiovascular disease are elevated levels of triglycerides, carried mostly in the very low density lipoprotein (VLDL) fraction. Drugs which lower serum lipids (i.e., hypolipemic drugs) frequently are prescribed to retard development of atherosclerotic lesions in individuals exhibiting hyperlipidemias. Many of these drugs are effective when taken regularly, but suffer from poor patient compliance due to unpleasant side effects. Examples of effective but underutilized hypolipemic drugs include the bile acid binding resins, such as cholestyramine. Web site: http://www.delphion.com/details?pn=US05773453__ •

N-hydroxyamide, N-hydroxythioamide, hydroxyurea, derivatives of selected nsaids as antiinflammatory agents

and

N-hydroxythiourea

Inventor(s): Belliotti; Thomas R. (Ypsilanti, MI), Cetenko; Wiaczeslaw A. (Ann Arbor, MI), Connor; David T. (Ann Arbor, MI), Flynn; Daniel L. (Mundelein, IL), Kostlan; Catherine R. (Saline, MI), Kramer; James B. (Sylvania, OH), Sircar; Jagadish C. (Ann Arbor, MI) Assignee(s): Warner-lambert Co. (morris Plains, Nj) Patent Number: 4,981,865 Date filed: May 26, 1989 Abstract: The present invention includes N-hydroxyamide, N-hydroxyurea, Nhydroxythioamide, and N-hydroxythiourea derivatives of fenamates, indomethacin, cicloprofen, oxepinac, and indoprofen as dual inhibitors or selective inhibitors of cyclooxygenase and 5-lipoxygenase. Excerpt(s): The present invention is novel compounds which are N-hydroxyamide, Nhydroxyurea, N-hydroxythioamide and N-hydroxythiourea derivatives of fenamate, indomethacin, cycloprofen, oxapinac and indoprofen, and pharmaceutically acceptable acid addition or base salts thereof, pharmaceutical compositions and methods of use therefor. The invention compounds are now found to have activity as dual inhibitors or selective inhibitors of 5-lipoxygenase and cyclooxygenase providing treatment of conditions advantageously affected by such inhibition including inflammation, arthritis, pain, fever, and the like. Thus, the present invention is also a pharmaceutical composition or method of use therefor. Specific hydroxamates of fenamic acid are shown in copending U.S. application Ser. No. 134,725 which includes a reference to European Application Publication No. 0,196,184 having broad disclosure of hydroxamic acid derivatives of selected aryl ring systems effective as high potency inhibitors of 5lipoxygenase. Summers et al also disclosed hydroxamic acid inhibitors of 5lipoxygenase in an abstract, September, 1987 and J. Med. Chem., 1987, 30, 574-80. Indole,

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benzofuran and benzothiophine each having an --A--N--C--R.sub.1 substituent is disclosed in European Application Publication No. 0279,263. Additionally various ring systems are known which are attached to a similar N--C containing substituent. For example, a (phenylalkoxy) phenyl; a biphenyl alkyl; a phenyl or naphthyl; 7-oxabicyclo (2.2.2) heptane; dibenzofuran; and (alkoxy) or (phenyloxy)-phenyl and naphthyl or thiofurane are disclosed in European Application Publication No. 279,281, British No. 2,191,194, PCT Application No. GB 86/00791, British No. 2,194,531, U.S. Pat. No. 4,769,387, and European Application Publication No. 292,699 respectively. European Application Publication No. 196,674 also discloses compounds including an --N--C-containing moiety having phenyl, naphthyl or sulfur heterocyclic ring systems attached directly or through various linking groups to the N of the moiety. The J. Org. Chem. 1989, 54, 1221-1223 and J. Med. Chem., 31, 1, pp. 3-5 (January 1988) disclose (hydroxy) or (phenylalkoxy)-phenyl, naphthyl and phenoxyphenyl rings in like manner attached to an --N--C-- containing substituent. However, none of the above noted disclosures describe hydroxamates of the configuration disclosed in this application on the selected nonsteroidal antiinflammatory type substrates. Web site: http://www.delphion.com/details?pn=US04981865__ •

Ointment and method for treating skin lesions due to herpes virus Inventor(s): Harendza-Harinxma; Alfred J. (50 Merion Place, Lawrenceville, NJ 08648) Assignee(s): None Reported Patent Number: 4,847,283 Date filed: June 9, 1987 Abstract: An ointment containing Indole or an Indole derivative such as Indican or Indomethacin as the active ingredient and a base. Also, a process for treating inflammations and lesions on the human skin including the step of applying an ointment containing the ointment to the lesion. Excerpt(s): This invention relates to compositions containing indole and indole derivatives, and a method for treatment of inflamation caused by herpes virus, including herpes zoster, herpes simplex I and herpes simplex II, using the aforesaid compositions. Since the middle ages, physicians have used urine for healing of various infectious diseases. The medical reference book Studio Medico-Chiurgico, by Dr. Samuel Schaarschmidt, published in 1760 reveals, at pages 348-349 that lesions caused by Gonorrhea may be healed in their early stages by washing the lesions repeatedly with urine, lime water or a mixture of both. The treatment and prevention of venereal infections using urine, continued until the end of World War II. During that time, physicians advised soldiers to urinate after intercourse and if possible to wash their penis with urine. The use of urine as a remedy to treat and prevent infectious diseases inspired the inventor to investigate the therapeutic qualities of the constituents of urine. Web site: http://www.delphion.com/details?pn=US04847283__

Patents 97

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Orally administrable pharmaceutical compositions Inventor(s): Evans; Brian K. (Dinas Powis, GB7), Rhodes; John (Cardiff, GB7) Assignee(s): Tillotts Pharma AG (ziefen, Ch) Patent Number: 5,541,170 Date filed: March 10, 1995 Abstract: A solid dosage form, such as a capsule or tablet, containing a pharmacologically active agent is coated with an anionic polymer, which is insoluble in gastric juice and in intestinal juice below pH7 but soluble in colonic intestinal juice, in a sufficient amount that the oral dosage form remains intact until it reaches the colon. The preferred anionic polymer is a partly methyl esterified methacrylic acid polymer in which the ratio of free carboxylic groups to ester groups is about 1:2. The invention has particular application to dosage forms of prednisolone and salts thereof, indomethacin, ibuprofen, and, especially, 5-amino-salicylic acid. Excerpt(s): The present invention relates to the administration of pharmacologically active agents to the large intestine and provides an orally administrable pharmaceutical composition for said purpose. It has particular, but not exclusive, application to the administration of 5-amino-salicylic acid (hereinafter referred to as 5-ASA) for the treatment of colonic or rectal disorders. In the treatment of diseases or ailments of the colon or rectum administration of the pharmacologically active agent to the affected site may be required. Orally administrable pharmaceutical compositions however have frequently been found ineffective in this respect as a result of the absorption of the pharmacologically active agent in the digestive tract before the colon or rectum is reached. Consequently, the delivery of pharmacologically active agents to the colon or rectum has conventionally been achieved by rectal administration, by the use of either suppositories or enemas. However, rectal administration generally is less convenient and less acceptable to a patient than oral administration. Further, said rectal administration is not suitable for treating the right side of the colon. In particular, suppositories are only effective lot the rectum and enemas rarely reach beyond the left side of the colon. Several "delayed release" forms of orally administrable pharmaceuticals have been proposed. The delayed release may result from the physical properties of the pharmaceutical composition or from the chemical and physical properties of a derivative of the active ingredient. It is known to provide tablets and capsules for oral administration with a coating which will disintegrate to release the pharmacologically active agent gradually when the tablet or capsule has reached the acid environment or the stomach or the alkaline environment or the small intestine. Similarly it is known to provide tablets and capsules with a coating permeable to the pharmacologically active agent contained within and through which the agent is gradually released. Web site: http://www.delphion.com/details?pn=US05541170__

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Pharmaceutical delivery systems Inventor(s): Flynn; Michael J. (Surrey, GB2), Story; Michael J. (Threapwood, GB2) Assignee(s): T.i.l. Medical Ltd. (middlesex, Gb2) Patent Number: 4,944,949 Date filed: December 17, 1987

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Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) including diclofenac, flufenamic acid, flurbiprofen, ibuprofen, indomethacin, ketoprofen, naproxen, phenylbutazone, piroxicam and sulindac are administered in micelles to alleviate their adverse effects on the gastrointestinal tract. The drugs are formulated with surfactants such as polyethoxylated nonionics to give micelle-forming compositions. Excerpt(s): This invention relates to pharmaceutical compositions for use in the treatment of inflammatory arthropathy. Inflammatory arthropathy is the general name for a collection of debilitating and painful diseases which are extremely common in many countries of the world. Their classification is somewhat difficult, but inflammatory arthropathy or rheumatic disease seem to be the most common generic terms. In this specification, the term "inflammatory arthropathy" is used as the preferred generic term, but is to be understood to include forms of the disease known to some practitioners as rheumatic disease. Of the various forms of inflammatory arthropathy, osteoarthrosis (or osteoarthritis) on the one hand and rheumatoid arthritis on the other hand are the commonest. Some workers in the field prefer the term osteoarthrosis to the term osteoarthritis, although it has been suggested that there is a place for both words. It is has been suggested that osteoarthrosis is the most sensible way of labelling the presence of simple degenerative joint disease but osteoarthritis separates the acute episodes of an inflammatory nature which occur in degenerative joint disease. Web site: http://www.delphion.com/details?pn=US04944949__ •

Pharmaceutical formulation containing indomethacin Inventor(s): Rainsford; Kim D. (No. 1 Butt Lane, Great Wilbraham, Cambridgeshire, GB2), Whitehouse; Michael W. (43 Malcolm Street, Millswood, South Australia, AU) Assignee(s): None Reported Patent Number: 4,885,279 Date filed: March 27, 1987 Abstract: A pharmaceutical preparation comprising indomethacin as active antiinflammatory drug and a metabolizable carbohydrate and a salt of a metabolic carboxylic acid and a metabolizable carbohydrate to protect both the stomach and the intestinal tract against damage by the drug. Excerpt(s): The invention relates to a pharmaceutical formulation containing the drug indomethacin. This formulation, when taken orally, prevents damage comprising ulceration, mucosal lesions, bleeding and peritonitis, to both the stomach as well as the lower regions of the small and large intestine. Certain anti-inflammatory drugs, in particular aspirin, are known to cause gastric damage, i.e. to the stomach, but no appreciable damage to the large or small intestine. In contrast, damage can be caused to the intestinal tract by indomethacin as well as that in the stomach. The former can be very severe and relatively high doses of the drug administered over a period of a few days have induced fatal peritonitis in laboratory rats. In rare instances, such fatal intestinal peritonitis as well as ulceration in the stomach have occurred in human patients treated with indomethacin. Although the damage to both the gastric mucosa and lower intestinal tract appears partly related to the activity of indomethacin as a potent inhibitor of prostaglandin synthesis, it is important to recognise that the mechanisms of gastric damage and damage to the lower portions of the intestinal tract are in fact quite different. The prostaglandins normally synthesised by certain cells on the surface of the gastrointestinal mucosa protect this tissue from the action of the many

Patents 99

irritating agents. Blockage of the synthesis of these natural protectants therefore exposes the mucosa of the gastrointestinal tract to other actions of these anti-inflammatory drugs, e.g. surface mucosal irritation, energy depletion, oxyradical-induced cell injury etc. Thus antigens normally present in the intestine, many of which are derived from the coliform bacteria that are normally present therein, enhance the damage in this region produced by indomethacin. Tests have shown that if no bacteria are present, indomethacin does not cause intestinal damage. It is also known that the unusual metabolism and pharmacokinetics of indomethacin which are responsible for the recycling of this drug from the bile to be absorbed back through the intestinal mucosa are a major feature accounting for damage in the latter region. Web site: http://www.delphion.com/details?pn=US04885279__ •

Pharmaceutical method and preparation containing indomethacin Inventor(s): Baudier; Philippe R. (Waterloo, BE), Deboeck; Arthur M. (Gurabo, PR), Fossion; Jacques J. (Braine-L'Alleud, BE), Maes; Paul J. (Vise, BE) Assignee(s): Pharlyse S.a. Societe Anonyme (luxembourg, Be) Patent Number: 5,036,100 Date filed: October 5, 1989 Abstract: This invention relates to a liquid pharmaceutical preparation for topical use on the skin of patients, said preparation containing indomethacin as active ingredient and dimethylisosorbide and isopropanol as excipients.The preparation according to the invention allows an easy and precise local administration by external application on the skin of a solution of indomethacin in the excipients. Excerpt(s): Among all the organs of the human body, the skin is the most accessible and extensive. Having a thickness of a few tenths of millimeter, the skin acts as a very efficient barrier against physical attacks and chemical agents. Since several centuries, many attempts have been made for treating topically body diseases, but a few positive results have only been obtained since a few decades. Particularly, in the field of inflammatory diseases, numerous treatments through the skin have been tried, for example, by means of product containing rubefacients. The latter cause a superficial feeling of warmth due to a local vasodilatation, but cause no decrease or only a small decrease of inflammation or pain. More recently, topical preparations containing corticosteroids or non-steroid antiinflammatory agents appeared on the market. The local treatment of inflammatory musculo-keletal affections is very interesting, since the pain is located in most cases in limited areas. An obvious psychological advantage of this type of treatment is that the painful area itself is treated and another advantage is that the oral administration may be avoided, so that it is possible to reduce and even to avoid completely the important systemic secondary effects which are important and frequently due to this type of drug, such as, for example, gastro-intestinal disorders. Web site: http://www.delphion.com/details?pn=US05036100__

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Preparation process for an aqueous pharmaceutical solution of an active principle constituted by an organic acid Inventor(s): Alain; Tournoux A. (Montpellier, FR), Coquelet; Claude (St Gely du Fese, FR), Maurin; Florence (Pignan, FR) Assignee(s): Laboratoires Chauvin-blache (fr) Patent Number: 4,866,088 Date filed: April 20, 1987 Abstract: Buffered opthalmic solutions of indomethacin. Excerpt(s): (c) at the time of use the product in a dry state is dissolved in a second aqueous solution containing the remainder of the buffer mixture, this remainder being such that the pH of the resulting solution is of a physiologically acceptable value. The present invention is concerned with a preparation process for an aqueous pharmaceutical solution of an active principle constituted by an organic acid normally considered as very slightly soluble or insoluble in water. The present invention is concerned more particularly with a preparation process for an aqueous pharmaceutical solution which contains notable quantities of such an active principle (generally from 0.05 to 5% by weight) and which is stable for at least one mouth in normal conditions of use. It is concerned in particular with a preparation process for ophthalmic solutions. Web site: http://www.delphion.com/details?pn=US04866088__

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Process for preparing pharmaceutical compositions for use with soft gelatin formulations Inventor(s): Ferdinando; Josephine Christine (Chippenham, GB), Lewis; Jacqueline Carol (Exmouth, GB), Tindal; Stephen Charles (Lakeside, GB), Webster; Christopher Clive (Chippenham, GB) Assignee(s): R.p. Scherer Technologies, Inc. (paradise Valley, Nv) Patent Number: 6,387,400 Date filed: August 29, 2000 Abstract: The invention disclosed herein is a process for increasing the achievable concentration of a pharmaceutically active ingredient relative to fill composition viscosity for dosage units. The process is particularly useful in the preparation of soft gelatin capsules containing ibuprofen, naproxen, indomethacin, and acetaminophen, as the pharmaceutically active ingredient. As a result of the process, lesser quantities of composition ingredients other than the pharmaceutically active ingredient are needed to accomplish the same therapeutically effective dosage, thereby significantly increasing the concentration of the pharmaceutically active ingredient resulting in either a reduction in overall fill volume and dosage unit size or an increase in concentration of pharmaceutically active ingredient per dosage form. Excerpt(s): The invention disclosed herein relates to the field of oral pharmaceutical formulations. In particular, the invention relates to an improved process for preparing pharmaceutical compositions for use in soft gel formulations. The inventive process allows for a given dose of active ingredient to be placed in a smaller dosage form. Filled one piece soft gels have been widely known and used for many years and for a variety of purposes. Because softgels have properties which are different from conventional telescoping two-piece hardshell capsules, the soft gels are capable of retaining liquid fill

Patents 101

material. Typically, softgels are used to contain orally consumable materials such as vitamins and pharmaceutical compositions in a liquid vehicle or carrier. In general, not all liquids are suitable as vehicles or carriers for inclusion in softgels. For example, water, propylene glycol, glycerin, low molecular weight alcohols, ketones, acids, amines and esters cannot be used as a carrier in softgels by themselves since they interact with the gel and, if present, they can only be present in relatively small amounts. Web site: http://www.delphion.com/details?pn=US06387400__ •

Ready-to-use indomethacin-based eye lotion Inventor(s): Coquelet; Claude (Saint Gely du Fesc, FR), Maurin; Florence (Vailhauques, FR), Pages; Bernard (Montbazin, FR) Assignee(s): Laboratoire Chauvin S.a. (montpellier Cedex 1, Fr) Patent Number: 5,744,154 Date filed: September 4, 1996 Abstract: The present invention relates to a ready-to-use indomethacin eye lotion comprising, in aqueous solution:indomethacin,a.beta.- or.gamma.-cyclodextrin etherified with C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 hydroxyalkyl groups, the cyclodextrin being present in a molar ratio with respect to the indomethacin of at least 10/1, and the pH of the solution being from 4.0 to 6.0. Excerpt(s): The present invention relates to a ready-to-use indomethacin-based eye lotion. It is known that indomethacin is a product which is substantially insoluble in water and that it is hydrolysed in the presence of water in alkaline medium. The use of various surfactants to dissolve indomethacin has already been recommended but the stability of the solutions obtained is not sufficient (Suleiman et al., Drug Development and Industrial Pharmacy, 16, 695, 1990) to make possible the manufacture of ready-touse eye lotions. Web site: http://www.delphion.com/details?pn=US05744154__

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Regulation of x-ray mediated gene expression Inventor(s): Hallahan; Dennis E. (Park Ridge, IL), Kufe; Donald W. (Wellesley, MA), Weichselbaum; Ralph R. (Chicago, IL) Assignee(s): Arch Development Corp. (chicago, Il), Dana-farber Cancer Institute (boston, Ma) Patent Number: 5,641,755 Date filed: July 20, 1994 Abstract: Treatment of cells with ionizing radiation is associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, protein kinase C induction and tumor necrosis factor gene expression. The addition of inhibitors of lipoxygenase, such as ketoconazole, prior to irradiation reduces the expression of of tumor necrosis factor while maintaining the expression of other radiation inducible genes, such as Egr-1 and c-jun. In contrast, indomethacin, an inhibitor of cyclooxygenase, enhanced the expression of tumor necrosis factor as well as other radiation inducible genes. The results show that lipoxygenase inhibitors are useful in the treatment of radiation-induced mucositis,

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dermatitis, pneumonitis, proctitis, and esophagitis. which may be due to the production of cytokines such as TNF. Excerpt(s): The present invention relates generally to the fields of radiation biology and cell biology. More particularly, it concerns the attenuation of the effect of ionizing radiation induced activation of cytokines, such as tumor necrosis factor, by inhibitors of extranuclear signal transduction. Tumor necrosis factor (TNF) is a polypeptide mediator of the inflammatory response and induces proliferation of fibroblasts, recruitment of inflammatory cells, activation of endothelial cells and hemorrhagic necrosis of tumors in mice (Fiers, 1991). Tumor necrosis factor also kills tumor cells directly through the induction of free radical formation and DNA fragmentation. These effects may explain the mechanism by which TNF enhances tumor cell killing by x-rays (Hallahan et al., 1990, Hallahan et al., 1989). Increased production of TNF is associated with inflammatory disorders such as autoimmune demyelination of the central nervous system and respiratory distress syndrome (Fiers, 1991). Tumor necrosis factor is produced by monocytes and macrophages in response to diverse stimuli, including ionizing radiation (Sherman et al., 1991, Wasserman et al., 1991). Increased TNF serum levels are associated with acute and subacute sequelae following total body irradiation (Holler et al., 1990). Radiation sequelae that correlate with TNF serum levels include pneumonitis, endothelial leakage syndrome, and veno-occlusive disease. Although, the effects of ionizing radiation on rapidly proliferating cell renewal systems have classically been theorized to be due to direct killing of stem cells within the injured organ, other work has suggested that TNF induction plays a role in the acute effects of irradiation by directly enhancing cell killing as well as mimicking the acute inflammatory response (Wong et al., 1991). Web site: http://www.delphion.com/details?pn=US05641755__ •

Sunburn treatment composition Inventor(s): Loomstein; Jack (9740 Bonhomme Estates Dr., Olivette, MO 63132) Assignee(s): None Reported Patent Number: 4,933,362 Date filed: June 6, 1989 Abstract: A composition for reducing heat and pain and preventing blistering in humans suffering from sunburn comprising indomethacin, benzocaine, and phenol in an aqueous alcoholic base. Excerpt(s): This invention relates to the treatment of sunburns in particular, relates to a composition for providing relief from the heat and pain of sunburn while also providing protection from infection and preventing blistering. A principal object of the present invention is to provide a composition and method for treating sunburn which provides relief for the heat and pain of the sunburned skin and also provides protection from infection and prevents blistering. Still another object is to provide a composition for treating a sunburn which has a combination of indomethacin, benzocaine, and phenol in a base of ethyl alcohol and water. Web site: http://www.delphion.com/details?pn=US04933362__

Patents 103

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Sustained-release preparation Inventor(s): Fujioka; Keiji (Amagasaki, JP), Sato; Shigeji (Ibaraki, JP), Yamahira; Yoshiya (Kobe, JP) Assignee(s): Sumitomo Pharmaceuticals Company, Limited (osaka, Jp) Patent Number: 4,855,134 Date filed: April 24, 1986 Abstract: A sustained-release preparation of indomethacin or interferon comprising the active ingredient in admixture with a pharmaceutically acceptable biodegradable carrier, particularly a carrier selected from collagen, gelatin, and a mixture thereof. The preparation is particularly suitable for parenteral administration and can release the active ingredient in an effective amount for a long period of time. Excerpt(s): 2 % antelocollagen (25 g) is dissolved in distilled water (100 ml), and indomethacin (0.5 g), is added thereto and the mixture is lyophilized to give a sustained-release preparation (A). 2 % atelocollagen (75 g) is dissolved in distilled water (300 ml), and indomethacin (0.5 g), is added thereto and the mixture is lyophilized to give a sustained-release preparation (B). Gelatin (10 g) is dissolved in distilled water (100 ml), indomethacin (0.5 g), is added thereto and the mixture is lyophilized to give a sustained-release preparation (C). Web site: http://www.delphion.com/details?pn=US04855134__

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Topical sod for treating hair loss Inventor(s): Proctor; Peter H. (Twelve Oaks Medical Tower 4126 SW. Freeway, Suite 1616, Houston, TX 77027) Assignee(s): None Reported Patent Number: 5,470,876 Date filed: April 18, 1994 Abstract: SOD for treating hair loss is disclosed. The SOD has utility in a topical pharmaceutical formulation for the cosmetic treatment of hair loss and the cosmetic stimulation of hair growth. The SOD comprises copper salicylate, copper aspirinate, indomethacin-copper, or a complex of an amino acid or peptide and a transition metal. Excerpt(s): This invention relates to topical superoxide dismutase (SOD), and the treatment of hair loss herewith. Recently, several anti-alopecia agents such as minoxidil and cyoctol have gained attention. However, most of these anti-alopecia agents are only minimally effective in some cases and/or can cause adverse dermatological or systemic reactions. Minoxidil, for example, is a therapeutic antihypertensive. Thus, the search continues for new, safer and more effective anti-alopecia agents which can be used without the risk of undesirable antihypertensive effects. Applicant has discovered that SOD can be used as a topical anti-alopecia agent which can desirably be essentially free of antihypertensives, for example, to stimulate cosmetic hair growth. Web site: http://www.delphion.com/details?pn=US05470876__

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Transdermal absorption preparation Inventor(s): Kiuchi; Chikako (Tokyo, JP), Ohtsuki; Tomohiro (Tokyo, JP), Yoshino; Yoshiko (Tokyo, JP) Assignee(s): Taisho Pharmaceutical Co., Ltd. (tokyo, Jp) Patent Number: 6,355,266 Date filed: April 14, 2000 Abstract: A transdermal absorption preparation containing.alpha.-form crystals of indomethacin in a vehicle. The present invention aims to provide an indomethacincontaining transdermal absorption preparation increased in the percutaneous absorption of indomethacin from the preparation, and improved in the stability of indomethacin in the preparation. Excerpt(s): The present invention relates to an indomethacin-containing transdermal absorption preparation. Preparations for external use, containing anti-inflammatory analgesics, such as indomethacin more effective than salicylic drugs, have been used as one of therapeutic drugs in the treatment of pain due to contusion, sprain or muscular fatigue, and pain associated with shoulder stiffness. These preparations have been useful in that they diminish systemic adverse reactions because of topical administration. However, the percutaneous absorption of indomethacin is not sufficient, so that indomethacin-containing transdermal absorption preparations hitherto used have been solutions. The solution type indomethacin is easily hydrolyzable and lacks stability. Indomethacin exists as.alpha.-form (needle-like),.beta.form, or.gamma.-form (platy) crystals because of polymorphism. The.gamma.-form is known as a stable form and the.alpha.-form as a meta-stable form. The conventional commercially available transdermal indomethacin preparations have contained the solution type indomethacin or the.gamma.-form crystals, and there have been no transdermal indomethacin preparations containing.alpha.-form crystals. Rectal absorption from suppositories containing.alpha.-form crystals of indomethacin has been reported to be better than that from suppositories containing.gamma.-form crystals (T. Yokoyama, Journal of the Pharmaceutical Society of Japan, 99, 837-842, 1979), but there have been no studies of the absorption of transdermal absorption preparations containing.alpha.-form crystals of indomethacin. Nor have there been any reports of the relationship between the crystal form of indomethacin and the stability of indomethacin in its preparations for external use. Web site: http://www.delphion.com/details?pn=US06355266__

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Treatment of Acquired Immunodeficiency Syndrome (AIDS) HTLV-111/LAV infections and Acquired Immunodeficiency Syndroms (AIDS) Related Complex (ARC) Inventor(s): McHugh; John E. (5139 Balboa Blvd., Ste. 1, Encino, CA 91316) Assignee(s): None Reported Patent Number: 4,970,233 Date filed: August 4, 1987 Abstract: There is disclosed a method of treating inflammatory viral infections of Acquired Immunodeficiency Syndrome (AIDS) HTLV-111/LAV virus and Acquired Immunodeficiency Syndrome (AIDS) Related Complex (ARC) in humans by stimulating

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and increasing the rate of Prostaglandin Biosynthesis to levels many times higher than that now occurring naturally thereby enhancing and reconstituting the Immune System, comprising the oral administration of an effective dosage of 3,3-Bis(p-hydroxyphenyl) phthalide (phenolphthalein) by itself or in composition with, or in combination with a Prostaglandin Synthetase inhibitor Aspirin or Indomethacin. Comprising the oral administration of an effective dosage of 3,3-Bis(p-hydroxyphenyl) phthalide (phenolphthalein) by itself or in composition with, or in combination with a Prostaglandins Synthetase inhibitor Aspirin or Indomethacin. Excerpt(s): This invention relates to the discovery that 3,3-Bis(phydroxyphenyl)phthalide (phenolphthalein) is an effective treatment for the viral infections Acquired Immunodeficiency Syndrome (AIDS) HTLF-111/LAV and Acquired Immunodeficiency Syndrome (AIDS) Related Complex C) in humans. Applicant also disclosed methods and uses of phenolphthalein as an antiviral drug in TREATMENT OF HERPES SIMPLEX INFECTIONS AND ACNE, U.S. Pat. No. 4,256,763, filed Sept. 19, 1978 and issued Mar. 17, 1981; and as an antiviral drug for treating mammalian inflammatory viral infections in U.S. Pat. Department No. 4,588,744 filed Jan. 27, 1981 and issued May 13, 1986. Acquired Immunodeficiency Syndrome (AIDS) HTLV-111/LAV virus is a sexually transmitted terminal disease that ravages the body's immune system and kills by a variety of infections, cancers and brain disorders. It has hit hardest at homosexuals and intravenous drug abusers in the United States, but it is a heterosexual disease in Africa and increasing numbers of cases of heterosexual transmission are being found in the United States and elsewhere. Web site: http://www.delphion.com/details?pn=US04970233__

Patent Applications on Indomethacin 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 indomethacin: •

Amide derivatives for antiangiogenic and/or antitumorigenic use Inventor(s): Kalgutkar, Amit S.; (Nashville, TN), Marnett, Lawrence J.; (Nashville, TN) Correspondence: Jenkins & Wilson, PA; 3100 Tower Blvd; Suite 1400; Durham; NC; 27707; US Patent Application Number: 20010034361 Date filed: March 27, 2001 Abstract: A method of treating animals having cancer by administration of secondary amide derivatives of various COOH-containing drugs, such as COOH-containing NSAIDs, for instance, indomethacin. Excerpt(s): The present invention, in general, relates to conversion of the carboxylic acid moiety of various compounds into amide derivatives of the compounds. More specifically, the present invention relates to secondary amide derivatives of nonsteroidal antiinflammatory drugs (NSAIDs), particularly of indomethacin (an NSAID), that exhibit inhibition of cyclooxygenase-2 (COX-2) far exceeding inhibition of

10

This has been a common practice outside the United States prior to December 2000.

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cyclooxygenase-1 (COX-1), and also, that still exhibit the analgesic, antiinflammatory, and/or antipyretic effect of the compound, i.e., of the NSAID, and moreover, also exhibit cancer inhibition, i.e., an antiangiogenic and/or antitumorigenic effect, in warm blooded vertebrate animals, including humans. As discussed in more detail below, the COX enzyme is really two enzymes, COX-1 and COX-2, which serve different physiological and pathophysiological functions. As is well known, at antiinflammatory and/or analgesic doses, indomethacin, aspirin, and other NSAIDs effect great inhibition of COX-1, which protects the lining of the stomach from acid, along with relatively minimal inhibition of COX-2, which provokes inflammation in response to joint injury or a disease like arthritis. Also, certain NSAIDs possess essentially the same inhibitory activity against both COX-1 and COX-2. Thus, zeroing in on inhibition of COX-2 alone has been the goal of drug developers for several years in order to reduce or eliminate the GI irritation caused by COX-1 inhibition. That COX activity originates from two distinct and independently regulated enzymes, termed COX-1 and COX-2, is described in DeWitt and Smith, "Primary Structure of Prostaglandin G/H Synthase from Sheep Vesicular Gland Determined from the Complementary DNA Sequence", Proc. Natl. Acad. Sci. U.S.A. (1988) Vol. 85, pp. 1412-1416; Yokoyama and Tanabe, "Cloning of Human Gene Encoding Prostaglandin Endoperoxide Synthase and Primary Structure of the Enzyme", Biochem. Biophys. Res. Commun. (1989) Vol. 165, pp. 888-894; and Hla and Neilson, "Human Cyclooxygenase-2-cDNA", Proc. Natl. Acad. Sci. U.S.A. (1992) Vol. 89, pp. 7384-7388. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating indomethacin responsive headaches Inventor(s): Galer, Bradley S.; (West Chester, PA), Newman, Lawrence; (Goldens Bridge, NY) Correspondence: Bret E. Field; Bozicevic, Field & Francis Llp; Suite 200; 200 Middlefield Road; Menlo Park; CA; 94025; US Patent Application Number: 20020143047 Date filed: January 5, 2001 Abstract: Methods and compositions, e.g., kits, are provided for treating a host suffering from an indomethacin responsive headache syndrome. In the subject methods, a topical indomethacin formulation is applied to a keratinized skin site proximal to the pain associated with the headache syndrome, e.g. a keratinized skin surface of the head, such as the forehead, temple, etc. Practice of the subject methods results in at least a reduction in the intensity of the pain associated with the syndrome. The subject methods and compositions find use in the treatment of a variety of indomethacin responsive headache syndromes, including syndromes that are absolutely responsive to indomethacin therapy and syndromes that are variably responsive to indomethacin therapy. Excerpt(s): The technical field of the invention is indomethacin-responsive headaches and the treatment thereof. The indomethacin-responsive headaches are a group of uncommon primary headache disorders that, by accepted definition of the International Headache Society Diagnostic Criteria, only demonstrate a prompt remission following therapy with indomethacin. The indomethacin responsive headaches can be further separated into two subcategories, based upon clinical features and degree of responsiveness to indomethacin. Those syndromes that exhibit an absolute response to therapy include the paroxysmal hemicranias and hemicrania continua. Syndromes

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exhibiting a variable response to therapy include idiopathic stabbing headaches (also called ice-pick headaches), and the benign forms of cough headache, exertional headache, and headaches associated with sexual activity. Unlike other primary headache disorders such as migraine, tension-type and cluster headaches, the indomethacin responsive headache conditions are resistant to treatment with all other classes of therapeutic agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic method for treatment of alzheimer's disease Inventor(s): Elsberry, Dennis D.; (New Hope, MN) Correspondence: Stephen W. Bauer; Medtronic, INC.; 710 Medtronic Parkway; Ms: Lc340; Minneaoplis; MN; 55432-5604; US Patent Application Number: 20010027309 Date filed: June 1, 2001 Abstract: A method and apparatus for treating Alzheimer's disease is disclosed. The method comprises delivering indomethacin or nonsteroidal anti-inflammatory agents having cyclooxygenase inhibitor action directly to the hippocampus or the lateral ventricle through an implanted catheter. The catheter has a flexible distal end that is implanted directly in the hippocampus or lateral ventricle as the preferred embodiment. The distal end has either a porous tip or a closed end. Where the distal end is closed, or a plurality of elution holes are present indomethacin is delivered to the hippocampus or lateral ventricle through either the porous tip or the elution holes. The catheter is part of a system for delivering indomethacin or nonsteroidal anti-inflammatory agents having cyclooxygenase inhibitor action to the hippocampus or lateral ventricle that includes a pump coupled to the catheter for delivering the indomethacin or nonsteroidal antiinflammatory agents having cyclooxygenase inhibitor action through the catheter to the hippocampus or lateral ventricle. Excerpt(s): This invention relates to a method of treating Alzheimer's disease and more specifically relates to delivering therapeutic nonsteroidal anti-inflammatory agents directly into the central nervous system or specific brain structures. Studies support an inverse relationship between anti-inflammatory medications used for treating patients with rheumatoid arthritis and an associated low prevalence of Alzheimer's disease [J. B. Rich et.al., Neurology 45:51-55, 1995]. Controlled studies of twin pairs having Alzheimer's disease onset greater than 3 years provide additional support that prior treatment with anti-inflammatory medications serves a protective role in Alzheimer's disease. [J. C. S. Breitner, et.,al., Neurology 44:227-232, 1994] Specifically, controlled double-blinded studies have found that the anti-inflammatory agent "indomethacin" administered orally has a therapeutic benefit for mild to moderately cognitively impaired Alzheimer's disease patients, and treatment with indomethacin during early stages of the disease has a retarding affect on disease progression compared to the placebo treated control group. [J. Rogers, et.al., Neurology 43:1609-1612, 1993] Alzheimner's patients with moderate cognitive impairment treated with indomethacin also exhibit a reduction in cognitive decline. However, patients treated with oral indomethacin developed drug related adverse effects that required their treatment to be discontinued and their removal from the study. Studies have shown indomethacin works at the cellular areas of the brain affected by Alzheimer's disease. These cellular areas include the hippocampus, entorhinal cortex, basal forebrain, amygdala and nucleus basalis of Meynert. In the normal brain, various enzyme systems act on amyloid

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precursor proteins to form peptides required for physiological brain functions including cellular membrane repair. 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 indomethacin, 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 “indomethacin” (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 indomethacin. You can also use this procedure to view pending patent applications concerning indomethacin. 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 6. PERIODICALS AND NEWS ON INDOMETHACIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover indomethacin.

News Services and Press Releases One of the simplest ways of tracking press releases on indomethacin 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 “indomethacin” (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 indomethacin. 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 “indomethacin” (or synonyms). The following was recently listed in this archive for indomethacin: •

Herbal supplement for prostate cancer contains indomethacin, DES and warfarin Source: Reuters Industry Breifing Date: April 10, 2002

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•

Indomethacin does not improve impairment-free survival of very low-birthweight infants Source: Reuters Industry Breifing Date: June 27, 2001

•

Indomethacin blunts the antihypertensive effects of captopril and losartan Source: Reuters Industry Breifing Date: October 06, 2000

•

Indomethacin protects against asthma exacerbations Source: Reuters Medical News Date: July 26, 2000

•

No adverse neurological effects from indomethacin treatment of preterm infants Source: Reuters Medical News Date: July 17, 2000

•

Ibuprofen as effective as indomethacin for ductal closure in preterm infants Source: Reuters Industry Breifing Date: July 12, 2000

•

Etoricoxib effective alternative to indomethacin in gout therapy Source: Reuters Industry Breifing Date: March 12, 2004

•

Prophylactic indomethacin does not reduce disability-free survival in preterms Source: Reuters Medical News Date: November 26, 2003

•

Indomethacin restores neurogenesis after brain inflammation Source: Reuters Industry Breifing Date: November 14, 2003

•

Indomethacin for recurrent patent ductus arteriosus unlikely to work if initial Doppler shows flow Source: Reuters Medical News Date: September 11, 2003

•

Indomethacin may increase serum phosphate in inherited hypophosphatemia Source: Reuters Medical News Date: September 02, 2003

•

Prolonged indomethacin not recommended for ductal closure in preemies Source: Reuters Medical News Date: August 04, 2003

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Parenteral indomethacin does not prevent cluster headache Source: Reuters Industry Breifing Date: May 02, 2003

•

Celecoxib appears safer than indomethacin for treatment of preterm labor Source: Reuters Industry Breifing Date: October 28, 2002

•

Indomethacin tocolysis does not increase risk of necrotizing enterocolitis Source: Reuters Industry Breifing Date: July 11, 2000

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•

American Academy of Neurology: Indomethacin a unique NSAID for headache relief Source: Reuters Medical News Date: April 23, 1999

•

Indomethacin may inhibit nitric oxide pathway activated in migraine Source: Reuters Medical News Date: March 17, 1999

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Indomethacin treats chronic daily bilateral headache Source: Reuters Medical News Date: August 31, 1998

•

Indomethacin Inhibits Tachyphylaxis To Acetaldehyde-Induced Bronchoconstriction In Asthma Source: Reuters Medical News Date: June 18, 1997

•

Indomethacin Suppositories: Effective In Patients With Rectal Polyposis Source: Reuters Medical News Date: October 15, 1996

•

MgSO4 Plus Indomethacin Offers Safe, Effective Tocolysis Source: Reuters Medical News Date: July 21, 1995 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “indomethacin” (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.

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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 “indomethacin” (or synonyms). If you know the name of a company that is relevant to indomethacin, 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 “indomethacin” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “indomethacin” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on indomethacin: •

Treating NDI: Emphasizing the First Year of Life Source: Endless Water. 4(4): 1-3. Fall 1999. Contact: Available from Diabetes Insipidus Foundation. 4533 Ridge Drive, Baltimore, MD 21229. (410) 247-3953. E-mail: [email protected]. Website: diabetesinsipidus.maxinter.net. Summary: Children with nephrogenic diabetes insipidus (NDI) are unable to concentrate their urine, requiring them to drink large volumes of water. This can impact them most during the first few years of life, when nutrition may take a backseat to preferential drinking. This article reviews patient care management strategies for these children, focusing on the first year of life. The fluid requirements in these children can be decreased in a number of ways, which may increase their caloric intake and improve their growth. Children with NDI usually fall from a growth status at or above the 50th percentile in height and weight at birth, to one below the 5th percentile during the first year. The causes of this growth failure may be due in part to inadequate caloric intake, as these children prefer water to food, milk, or formula. However, additional contributing factors may include bouts of dehydration or the presence of gastrointestinal (GI) symptoms such as disturbances in GI motility, reflux, or early satiety. Therapy for NID may include a combination of one of three medications including indomethacin (Indocin), amiloride (Midamor), and hydrochlorothiasize (Hydrodiuril) or chlorothiazide (Diuril). Salt reduction is a major focus of nutritional therapy of NDI. In addition, nutritional therapy must be undertaken to maximize caloric intake to promote

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adequate growth or even 'catch up' growth. The authors outline strategies to increase caloric content of the infant's formula. Enteral nutrition (tube feedings) may be indicated if the child is not able to consume adequate calories. The authors conclude that nutritional assessment and intervention in NDI needs to be an ongoing process that starts early in the first year of life, with special attention paid to the fact that every child has unique nutritional habits and needs. •

Keep an Eye on These Drugs: Possible Aggravators of Psoriasis Source: Psoriasis Resource. 3(2): 11. July 2001. Contact: Available from National Psoriasis Foundation. 6600 SW 92nd Avenue, Suite 300, Portland, OR 97223-7195. (800) 723-9166 or (503) 244-7404. Fax (503) 245-0626. Email: [email protected]. Website: www.psoriasis.org. PRICE: Contact NPF for current pricing. Summary: This newsletter article provides people who have psoriasis with information on drugs that can worsen this condition. One such drug is lithium, which is used to treat manic depression and other psychiatric disorders and which aggravates psoriasis in about 50 percent of those who take it. However, several alternatives to lithium are available. Carbamazepine, which is sometimes prescribed for the same mood disorders as lithium, has no history of worsening psoriasis. Valproic acid is another anticonvulsant that has been used as an alternative to lithium. Other medications that can cause psoriasis to flare are antimalarials such as quinacrine, chloroquine, and hydroxychloroquine; Inderal; quinidine; and indomethacin.

Academic Periodicals covering Indomethacin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to indomethacin. In addition to these sources, you can search for articles covering indomethacin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 7. 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 indomethacin. 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 non-profit 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 indomethacin. 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 indomethacin: Anti-Inflammatory Drugs, Nonsteroidal •

Ophthalmic - U.S. Brands: Ocufen; Profenal; Voltaren Ophthalmic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202647.html

•

Systemic - U.S. Brands: Actron; Advil; Advil Caplets; Advil, Children's; Aleve; Anaprox; Anaprox DS; Ansaid; Bayer Select Ibuprofen Pain Relief Formula Caplets; Cataflam; Clinoril; Cotylbutazone; Cramp End; Daypro; Dolgesic; Dolobid; EC-Naprosyn; Excedrin IB http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202743.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

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

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

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

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

•

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

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.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

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

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

•

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 “indomethacin” (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 33087 129 999 19 131 34365

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 “indomethacin” (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 indomethacin 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 indomethacin. 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 indomethacin. 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 “indomethacin”:

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Other guides Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Cartilage Disorders http://www.nlm.nih.gov/medlineplus/cartilagedisorders.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Medicines http://www.nlm.nih.gov/medlineplus/medicines.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 Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on indomethacin. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Gouty Arthritis Source: Physician Assistant. 23(11): 45-46. November 1999. Summary: This information sheet uses a question and answer format to provide people who have gouty arthritis with information on this disease, which produces swelling in one or more joints as a result of deposits of uric acid. Gouty arthritis, which is commonly called gout, occurs in 2 to 2.6 per 1,000 people in the United States. In the first phase of gout, known as asymptomatic hyperuricemia, the blood has high levels of uric acid but the person has no symptoms. In the next phase, gout causes pain, stiffness, and swelling in the affected joint. The third phase, known as intercritical gout, is the phase between attacks. In the final phase, accumulations of hard crystals of uric acid, called tophi, are deposited in various areas of the body. Diagnosis is based on a physical examination, blood tests, and x rays. Acute attacks of gout may be treated with nonsteroidal anti-inflammatory drugs, colchicine, corticosteroids, and adrenocorticotropic hormones. Nonpharmacologic methods of treating acute attacks include bedrest, hot or cold compresses, and elevation of the affected joint. Preventing future attacks involves following a diet low in purine; increasing fluid intake to 3 liters per day; losing weight; and taking medications such as colchicine, indomethacin, probenecid, sulfinpyrazone, and allopurinol. 1 figure.

Patient Resources 127

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 indomethacin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: 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 indomethacin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with indomethacin. 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 indomethacin. 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

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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 “indomethacin” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received 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 “indomethacin”. 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 “indomethacin” (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 “indomethacin” (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

•

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

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

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

•

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.

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•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

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

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

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/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

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/

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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

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

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/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

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

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

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

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

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

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on indomethacin: •

Basic Guidelines for Indomethacin Indocin overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002657.htm

•

Signs & Symptoms for Indomethacin Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Blurred vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm

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Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Nausea and/or vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Ringing in the ears Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003043.htm Stomach pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Unsteadiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Background Topics for Indomethacin Unconscious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

Online Glossaries 137

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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INDOMETHACIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH]

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Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [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] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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.

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[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] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH]

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Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] 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 Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] 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] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve

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function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] 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 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] 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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] 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] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthelmintic: An agent that is destructive to worms. [EU] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective

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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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] 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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [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] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a

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peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] 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] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arthropathy: Any joint disease. [EU] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] 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] 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] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording

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entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] 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]

Benzocaine: A surface anesthetic that acts by preventing transmission of impulses along nerve fibers and at nerve endings. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its

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composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] 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 modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH]

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Blepharitis: Inflammation of the eyelids. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Flow Velocity: A value equal to the total volume flow divided by the cross-sectional area of the vascular bed. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [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] 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 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

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trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] 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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [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]

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Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] 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]

Cardiac: Having to do with the heart. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule,

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especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange

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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] Cephaloridine: A cephalosporin antibiotic. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] 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] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [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] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in

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response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorion: The outermost extraembryonic membrane. [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 renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis,

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it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] 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] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] 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] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but

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now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [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] 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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU]

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Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]

Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Contusion: A bruise; an injury of a part without a break in the skin. [EU] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to

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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 Circulation: The circulation of blood through the coronary vessels of the heart. [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] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] 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] Craniotomy: An operation in which an opening is made in the skull. [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] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.

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[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] 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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure.

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The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [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] Dermatitis: Any inflammation of the skin. [NIH] Dermatologic Agents: Drugs used to treat or prevent skin disorders or for the routine care of skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] 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] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel

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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] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or 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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [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] Dysgenesis: Defective development. [EU] Dysmenorrhea: Painful menstruation. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from

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arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emollient: Softening or soothing; called also malactic. [EU] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph

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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] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [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] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] 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] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] 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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth

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factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Episiotomy: An incision of the posterior vaginal wall and a portion of the pudenda which enlarges the vaginal introitus to facilitate delivery and prevent lacerations. [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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [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] Evacuation: An emptying, as of the bowels. [EU]

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Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] 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] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] 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] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH]

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Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] 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] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell

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sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting carbonic anhydrase. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [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 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] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH]

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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] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] 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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Fundus: The superior portion of the body of the stomach above the level of the cardiac notch. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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] 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]

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Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] 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 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] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] 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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH]

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Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] 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] Guanfacine: A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Haematemesis: The vomiting of blood. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haloperidol: Butyrophenone derivative. [NIH]

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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] Hemicrania: An ache or a pain in one side of the head, as in migraine. [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]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [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] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

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] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H,

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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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [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] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH]

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Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [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] 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] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] 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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also

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inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local 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]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infuse: To pour (a liquid) into something. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] 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] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH]

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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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [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 Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [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]

Investigative Techniques: Investigative techniques used in pre-clinical and clinical research, epidemiology, chemistry, immunology, genetics, etc. They do not include techniques

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specifically applied to diagnosis; therapeutics; anesthesia and analgesia, surgery, operative, and dentistry. [NIH] Involuntary: Reaction occurring without intention or volition. [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] Ipsilateral: Having to do with the same side of the body. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Isosorbide Dinitrate: A vasodilator used in the treatment of angina. Its actions are similar to nitroglycerin but with a slower onset of action. [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] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH]

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Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [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] Lacerations: Torn, ragged, mangled wounds. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] 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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] 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] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]

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Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [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] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH]

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Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung volume: The amount of air the lungs hold. [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] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malformation:

A

morphologic

defect

resulting

from

an

intrinsically

abnormal

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developmental process. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [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] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH]

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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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metalloporphyrins: Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from

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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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase

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kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [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] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH]

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Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH]

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Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] 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] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or

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effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [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] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] 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] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] NSAIDs: Nonsteroidal anti-inflammatory drugs. A group of drugs that decrease fever, swelling, pain, and redness. [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

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the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oesophagitis: Inflammation of the esophagus. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] 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] Organ Specificity: Restriction of a characteristic or response to a particular organ of the body; it usually refers to that property of the immune response which differentiates one organ from another on the basis of antigen recognition, but the concept is not limited to immunology. [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] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more

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concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] 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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH]

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Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palliative therapy: Treatment given to relieve symptoms caused by advanced cancer. Palliative therapy does not alter the course of a disease but improves the quality of life. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] 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] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Par excellence: The petrous portion of the temporal bone, containing the inner ear and wedged in at the base of the skull between the sphenoid and occipital bones. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patent ductus arteriosus: Abnormal persistence of the opening in the arterial duct that connects the pulmonary artery to the descending aorta; this opening normally closes within 24 hours of birth. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Management: Generating, planning, organizing, and administering medical

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and nursing care and services for patients. [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] 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] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [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] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU]

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Perivascular: Situated around a vessel. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] 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] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylbutyrate: An anticancer drug that belongs to the family of drugs called differentiating agents. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or

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glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Piloerection: Involuntary erection or bristling of hairs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Components: The anatomical components of a plant, including seeds. [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

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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 protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polyhydramnios: Excess of amniotic fluid greater than 2,000 ml. It is a common obstetrical complication whose major causes include maternal diabetes, chromosomal disorders, isoimmunological disease, congenital abnormalities, and multiple gestations. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same

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population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is

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indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Pregnenolone: Steroid hormone. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed

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over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in 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] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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 Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein

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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] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudomembranous Colitis: Severe irritation of the colon. Caused by Clostridium difficile bacteria. Occurs after taking oral antibiotics, which kill bacteria that normally live in the colon. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the

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term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] 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] Quinacrine: N(4)-(6-Chloro-2-methoxy-9-acridinyl)-N(1),N(1)-diethyl-1,4-pentanediamine. An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH]

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Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [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] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be

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in a randomized trial. [NIH] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [NIH] Ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes. The protooncogene-derived protein (proto-oncogene protein P21(RAS)) plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (oncogene protein P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation). EC 3.6.1.-. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectovaginal Fistula: Abnormal communication between the rectum and the vagina. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] 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]

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Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [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 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] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH]

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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] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] 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] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH]

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Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second cancer: Refers to a new primary cancer that is caused by previous cancer treatment, or a new primary cancer in a person with a history of cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] 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] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senile Plaques: Spherical masses consisting of amyloid fibrils and neuronal processes. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3.

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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] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] 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]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] 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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the

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large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Socialization: The training or molding of an individual through various relationships, educational agencies, and social controls, which enables him to become a member of a particular society. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium salicylate: A drug that belongs to the family of drugs called nonsteroidal antiinflammatory drugs. Sodium salicylate may be tolerated by people who are sensitive to aspirin. [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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [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] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] 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] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] 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

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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] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress Fibers: Bundles of actin filaments (microfilaments) and myosin-II that span across the cell attaching to the cell membrane at focal adhesions and to the network of intermediate filaments that surrounds the nucleus. [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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] 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

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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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] 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] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfinpyrazone: A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] 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] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic

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nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole 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] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terminal disease: Disease that cannot be cured and will cause death. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH]

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Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] 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] Tocolysis: Any drug treatment modality designed to inhibit uterine contractions in pregnant women at risk for preterm labor. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonicity: The normal state of muscular tension. [NIH]

Dictionary 211

Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH]

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Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] 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] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ulcerogenic: Causing ulceration; leading to the production of ulcers. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder.

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[NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinate: To release urine from the bladder to the outside. [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] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs

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and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] War: Hostile conflict between organized groups of people. [NIH]

Dictionary 215

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. 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]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] 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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH] Zygote: The fertilized ovum. [NIH]

217

INDEX A Abdomen, 139, 148, 173, 176, 179, 191, 206, 207 Abdominal, 139, 152, 154, 176, 182, 190, 191, 212 Abdominal Pain, 139, 191, 212 Aberrant, 22, 139, 201 Abrasion, 35, 139 Acatalasia, 139, 150 Acceptor, 139, 179, 189 Acetaminophen, 93, 100, 139 Acetylcholine, 139, 153, 187 Actin, 13, 48, 139, 183, 185, 207, 212 Adaptability, 139, 151 Adaptation, 22, 139, 194 Adduct, 8, 139 Adenocarcinoma, 53, 77, 139 Adenoma, 13, 51, 139 Adenosine, 139, 149, 193 Adhesions, 13, 140, 207 Adjustment, 139, 140 Adjuvant, 5, 17, 20, 140, 141, 168 Adjuvant Therapy, 17, 140 Adrenal Cortex, 140, 141, 157, 164, 196, 202 Adrenal Medulla, 140, 151, 164, 187 Adrenergic, 140, 161, 164, 199, 208 Adsorptive, 65, 140 Adverse Effect, 4, 5, 8, 9, 55, 98, 107, 140, 205, 214 Aerobic, 140, 189 Aerobic Metabolism, 140, 189 Aerobic Respiration, 140, 189 Aerosol, 140, 208, 214 Afferent, 90, 140 Affinity, 29, 140, 141, 179, 206 Agar, 140, 193 Age of Onset, 141, 212 Agonist, 141, 150, 160, 161, 187, 208 Airway, 21, 141 Albumin, 10, 141, 194, 209 Aldosterone, 39, 141 Alertness, 141, 149 Algorithms, 141, 147 Alimentary, 64, 66, 67, 141, 190 Alkaline, 14, 97, 101, 141, 149, 192 Alkaloid, 141, 154, 184, 187, 199 Allantois, 141, 166

Allergen, 141, 159, 204 Allopurinol, 92, 126, 141 Alopecia, 103, 141 Alpha Particles, 141, 200 Alternative medicine, 111, 141 Aluminum, 84, 141 Aluminum Hydroxide, 84, 141 Alveoli, 142, 214 Amebiasis, 142, 183 Amine, 142, 172 Amino Acids, 142, 191, 195, 198, 208 Amlodipine, 39, 142 Amnion, 142, 166 Amniotic Fluid, 11, 39, 142, 169, 181, 194 Amphetamines, 142, 154 Amplification, 90, 142 Ampulla, 142, 162 Amygdala, 107, 142, 179 Amyloid, 9, 18, 93, 107, 142, 204 Anaerobic, 28, 142, 207 Anaesthesia, 61, 62, 66, 142, 175 Analgesic, 12, 19, 43, 85, 89, 106, 139, 142, 159, 167, 173, 178, 184, 188, 199, 208 Analog, 31, 142, 167 Anatomical, 142, 145, 148, 156, 160, 174, 190, 193 Anesthesia, 33, 42, 141, 142, 177, 196 Aneurysm, 143, 213 Angina, 82, 142, 143, 177, 187 Angina Pectoris, 82, 142, 143 Angiogenesis, 143, 181 Animal model, 19, 27, 143 Anionic, 97, 143 Anions, 141, 143, 177, 196, 205, 208 Anorexia, 89, 142, 143 Antagonism, 143, 149 Anterior chamber, 91, 143, 177 Anthelmintic, 143, 199 Antiangiogenic, 105, 106, 143 Antibacterial, 84, 85, 143, 151, 196, 206 Antibiotic, 85, 94, 143, 148, 152, 183, 206, 210 Antibodies, 143, 146, 171, 174, 180 Antibody, 31, 69, 140, 143, 144, 155, 171, 172, 174, 175, 177, 181, 184, 200, 205, 206, 215 Anticoagulant, 143, 197, 215 Anticonvulsant, 113, 143

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Indomethacin

Antidepressant, 143, 167 Antidiuretic, 143, 186 Antifungal, 89, 143, 177 Antigen, 140, 143, 144, 155, 172, 173, 174, 175, 181, 188, 204 Antihypertensive, 39, 103, 110, 144, 170 Anti-Inflammatory Agents, 5, 83, 85, 92, 107, 144, 145, 157, 178 Antimetabolite, 144, 167 Antimicrobial, 84, 87, 144 Antineoplastic, 144, 157, 167, 173 Antioxidant, 22, 144, 145, 168, 189 Antiproliferative, 33, 34, 144 Antipruritic, 144, 153 Antipyretic, 72, 85, 89, 106, 139, 144, 159, 167, 178, 199 Antithrombotic, 144, 197 Antiviral, 105, 144, 176 Anus, 144, 148, 166, 201 Anxiety, 25, 90, 144 Aorta, 67, 144, 161, 190, 214 Apolipoproteins, 144, 179 Apoptosis, 9, 11, 34, 36, 37, 40, 46, 50, 53, 67, 68, 144 Aqueous, 36, 72, 89, 91, 100, 101, 102, 144, 146, 153, 158, 173, 178 Aqueous humor, 91, 144, 153 Arachidonate 12-Lipoxygenase, 144, 179 Arachidonate 15-Lipoxygenase, 145, 179 Arachidonate Lipoxygenases, 145, 179 Arachidonic Acid, 8, 10, 12, 13, 21, 22, 25, 27, 28, 101, 144, 145, 162, 178, 179, 197 Arginine, 20, 87, 145, 187 Arterial, 12, 23, 28, 41, 145, 150, 153, 173, 187, 190, 198, 209 Arteries, 12, 23, 29, 144, 145, 148, 150, 152, 153, 157, 180, 183, 185, 210 Arterioles, 145, 148, 149, 183, 185 Arteriosus, 26, 145, 199 Arteriovenous, 145, 183 Arthropathy, 98, 145 Arthroplasty, 49, 52, 53, 59, 60, 145 Articular, 145, 189 Ascorbic Acid, 8, 145, 173 Aspirin, 8, 14, 27, 34, 40, 58, 62, 67, 85, 93, 94, 98, 105, 106, 145, 206 Astringents, 145, 182 Astrocytoma, 145, 169 Asymptomatic, 49, 126, 139, 142, 145 Atherogenic, 95, 145 Atrial, 145, 215 Atrial Fibrillation, 145, 215

Atrium, 145, 214 Attenuated, 24, 146 Attenuation, 92, 93, 102, 146 Autacoids, 146, 174 Autoantibodies, 93, 146 Autoantigens, 146 Autonomic, 45, 55, 139, 146, 187, 191 Axons, 20, 146, 159, 186, 188 B Bacterial Physiology, 139, 146 Bactericidal, 146, 164 Bacteriophage, 146, 194, 211 Bacterium, 14, 146, 156 Basal Ganglia, 146, 169, 179, 199 Base, 95, 96, 102, 146, 158, 159, 177, 190, 192, 209 Basement Membrane, 13, 146, 165, 178 Basophils, 48, 146, 170, 178 Benign, 93, 107, 139, 146, 171, 185, 200, 204 Benzocaine, 102, 146 Beta-pleated, 142, 146 Bilateral, 4, 35, 111, 146, 190 Bile, 6, 18, 95, 99, 146, 147, 153, 163, 168, 179, 181, 207 Bile Acids, 147, 207 Bile Acids and Salts, 147 Bile Ducts, 6, 147 Bile Pigments, 147, 181 Biliary, 6, 147, 149, 153 Bilirubin, 141, 147 Biochemical, 24, 37, 47, 86, 144, 147, 166, 178, 189, 192, 205 Biological response modifier, 147, 176 Biological therapy, 147, 170 Biomarkers, 6, 147 Biopsy, 147, 191 Biosynthesis, 19, 105, 145, 147 Biotechnology, 30, 31, 111, 121, 147 Biotransformation, 9, 147 Bladder, 8, 147, 167, 197, 212, 213 Blastocyst, 147, 155, 193 Blepharitis, 15, 148 Blood Coagulation, 148, 149, 166 Blood Flow Velocity, 35, 52, 148 Blood Glucose, 62, 148, 171, 176 Blood Platelets, 148, 205 Blood pressure, 20, 39, 144, 148, 150, 173, 184, 206 Blood-Brain Barrier, 93, 148 Body Fluids, 147, 148, 161, 206, 212 Body Regions, 148, 154 Bolus, 35, 53, 86, 148

Index 219

Bolus infusion, 35, 148 Bone Marrow, 148, 174, 180, 184 Bowel, 148, 159, 163, 176, 191, 207, 212 Bowel Movement, 148, 160, 207 Brachytherapy, 148, 176, 177, 200, 215 Bradykinin, 148, 187, 194 Branch, 133, 148, 180, 190, 206, 209, 210 Breakdown, 93, 148, 159, 168 Broad-spectrum, 148, 151 Bronchi, 148, 149, 164 Bronchial, 21, 149, 172, 197 Bronchopulmonary, 26, 46, 149 Bronchopulmonary Dysplasia, 26, 46, 149 Buccal, 149, 180 Bupivacaine, 149, 178 C Caffeine, 42, 72, 149 Calcium, 37, 74, 142, 149, 155, 181, 197, 198, 205, 212 Calcium channel blocker, 142, 149 Calculi, 149, 170 Caloric intake, 112, 149 Candidiasis, 89, 149 Candidosis, 149 Cannabidiol, 149 Cannabinoids, 5, 149 Cannabinol, 149 Capillary, 148, 149, 150, 151, 214 Capillary Fragility, 150, 151 Capsules, 97, 100, 150, 161, 168 Captopril, 39, 110, 150 Carbachol, 14, 150 Carbohydrate, 98, 150, 157, 169, 195 Carbon Dioxide, 150, 158, 166, 168, 173, 193, 202 Carcinogen, 22, 139, 150, 183 Carcinogenesis, 24, 50, 150, 152 Carcinogenic, 13, 150, 175, 207, 212 Carcinoma, 40, 54, 67, 83, 150 Cardiac, 37, 40, 62, 145, 149, 150, 160, 162, 164, 165, 168, 178, 185, 199, 207 Cardiotonic, 150, 160 Cardiovascular, 26, 29, 95, 150, 178, 205 Cardiovascular disease, 95, 150 Carotid Arteries, 23, 150 Case report, 3, 150, 154 Case series, 150, 154 Castor Oil, 82, 150 Catalase, 9, 139, 150 Cataract, 68, 150 Catechin, 84, 151 Catecholamine, 151, 160, 192

Catheters, 11, 151, 174, 176 Caudal, 151, 173, 195 Cecum, 151, 178 Ceftazidime, 31, 151 Cell Cycle, 151, 154 Cell Death, 26, 144, 151, 185 Cell Differentiation, 151, 205 Cell Division, 146, 151, 170, 181, 184, 193, 196 Cell membrane, 14, 151, 159, 193, 207 Cell proliferation, 18, 22, 151, 205 Cell Respiration, 140, 151, 189, 202 Cell Size, 151, 167 Cell Survival, 151, 170 Cellobiose, 151 Cellulose, 8, 151, 167, 193 Central Nervous System Infections, 152, 171, 172 Cephaloridine, 151, 152 Cerebral Arteries, 29, 152 Cerebral hemispheres, 146, 152, 169 Cerebral Palsy, 11, 78, 152 Cerebrospinal, 152, 172, 205 Cerebrospinal fluid, 152, 172, 205 Cerebrovascular, 25, 29, 49, 150, 152 Cerebrum, 152 Ceroid, 152, 179 Cervical, 50, 152 Cervix, 152 Cesarean Section, 11, 152 Character, 143, 152, 158 Chemokines, 47, 152 Chemopreventive, 12, 14, 22, 152 Chemotactic Factors, 152, 155, 187 Chemotaxis, 45, 152 Chemotherapy, 67, 77, 83, 140, 153 Cholesterol, 8, 95, 147, 153, 157, 179, 180, 207 Cholesterol Esters, 153, 179 Cholestyramine, 95, 153 Choline, 6, 43, 153 Cholinergic, 8, 150, 153, 187 Chorion, 153, 166 Chromatin, 144, 153, 163 Chromosomal, 142, 153, 194 Chromosome, 153, 156, 179 Chronic renal, 153, 167 Chylomicrons, 153, 179 Ciliary, 144, 145, 153, 213 Ciliary Arteries, 145, 153 Ciliary Body, 145, 153, 213 Ciliary processes, 144, 153

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Indomethacin

Circulatory system, 153, 162, 176 CIS, 50, 153 Cisplatin, 65, 153 Citrus, 145, 154 Clinical Medicine, 154, 195 Clinical study, 34, 154, 156 Clinical trial, 4, 8, 17, 77, 78, 121, 154, 156, 161, 200 Cloning, 19, 106, 147, 154 Coagulation, 148, 154, 171, 194, 210, 215 Coca, 154 Cocaine, 15, 154 Coenzyme, 145, 154 Colchicine, 4, 35, 92, 126, 154 Colic, 63, 154 Colitis, 94, 154 Collagen, 13, 15, 82, 88, 91, 103, 146, 151, 154, 165, 166, 168, 181, 194, 196, 204 Collagen disease, 154, 204 Collapse, 148, 155 Colloidal, 88, 141, 155, 205, 208 Colorectal, 33, 50, 77, 155 Colorectal Cancer, 33, 50, 77, 155 Combination chemotherapy, 83, 155 Communis, 150, 155 Complement, 155, 168, 194, 205 Complete remission, 155, 202 Computational Biology, 121, 155 Conception, 155, 166 Cone, 155, 208 Congestion, 155, 164 Conjugated, 9, 147, 156, 158 Conjugation, 10, 18, 147, 156 Conjunctiva, 15, 153, 156, 175, 177, 204, 212 Conjunctivitis, 15, 87, 156 Connective Tissue, 145, 148, 154, 156, 166, 168, 180, 182, 203 Consciousness, 142, 156, 158, 160 Constipation, 3, 156, 170, 191 Constriction, 12, 64, 156, 177, 198, 213 Constriction, Pathologic, 156, 213 Contact dermatitis, 33, 156 Contractility, 11, 156 Contraindications, ii, 156 Control group, 107, 156, 196, 200 Controlled clinical trial, 17, 156 Contusion, 104, 156 Conventional therapy, 156 Conventional treatment, 7, 83, 156 Convulsions, 136, 143, 156

Cornea, 91, 143, 144, 156, 177, 204, 207, 213 Coronary, 12, 143, 150, 157, 183, 185, 187 Coronary Circulation, 143, 157, 187 Coronary heart disease, 150, 157 Coronary Thrombosis, 157, 183, 185 Corpus, 157, 169, 186, 191, 196 Cortex, 152, 157, 163 Cortical, 52, 157, 204 Corticosteroid, 157, 195 Cortisol, 141, 157 Cortisone, 157, 159, 196 Cranial, 157, 171, 176, 186, 188, 191, 206, 212 Craniocerebral Trauma, 157, 171, 172 Craniotomy, 66, 157 Curative, 157, 187, 210 Cutaneous, 20, 24, 94, 149, 156, 157, 173, 180 Cyclic, 21, 36, 86, 149, 157, 170, 187, 195, 197 Cysteine, 18, 152, 157, 208 Cystine, 157 Cytochrome, 53, 158 Cytokine, 11, 51, 54, 67, 90, 158 Cytoplasm, 144, 146, 151, 158, 163, 170, 184 Cytotoxic, 6, 48, 158, 174, 200, 205 Cytotoxicity, 6, 16, 50, 87, 154, 158 D Databases, Bibliographic, 121, 158 Decarboxylation, 158, 172 Decidua, 11, 55, 158, 193 Degenerative, 98, 158, 171, 189, 203 Dehydration, 18, 112, 158 Deletion, 144, 158 Delusions, 158, 198 Dementia, 3, 15, 19, 158 Dendrites, 158, 159, 186 Density, 91, 95, 158, 167, 179, 188, 194 Dentate Gyrus, 158, 172 Dentifrices, 141, 159 Deoxyguanosine, 8, 159 Depolarization, 159, 205 Depressive Disorder, 159, 179 Dermatitis, 33, 102, 159 Dermatologic Agents, 159 Desensitization, 34, 159 Deuterium, 159, 173 Dexamethasone, 5, 11, 45, 68, 159 Diabetes Insipidus, 112, 159 Diabetes Mellitus, 159, 169, 171

Index 221

Diagnostic procedure, 81, 111, 159 Diarrhea, 136, 142, 153, 159 Diastolic, 159, 170, 173 Diastolic blood pressure, 159, 170 Diclofenac, 33, 65, 85, 93, 98, 159 Diclofenac Sodium, 65, 159 Diffusion, 159, 175 Digestion, 141, 147, 148, 159, 161, 176, 179, 191, 207 Digestive system, 79, 159, 184 Digestive tract, 97, 160, 205, 206, 207, 215 Dihydrotestosterone, 160, 201 Dilatation, 143, 160, 213 Dilatation, Pathologic, 160, 213 Dilation, 148, 160, 172, 213 Dilator, 23, 25, 160, 187 Direct, iii, 15, 22, 46, 93, 102, 115, 154, 160, 161, 169, 180, 199, 201 Disease Progression, 19, 107, 160 Disinfectant, 160, 164 Disposition, 18, 31, 160 Dissociation, 12, 140, 160, 177 Dissociative Disorders, 160 Distal, 107, 160, 162, 198 Distention, 23, 160 Diuresis, 149, 160 Diuretic, 160, 167, 177, 208 Dobutamine, 29, 160 Docetaxel, 6, 160 Domesticated, 160, 170 Dopamine, 5, 29, 34, 37, 62, 154, 160, 192 Dorsal, 161, 195 Dosage Forms, 97, 161 Dose-dependent, 8, 161 Double-blinded, 107, 161 Drug Interactions, 116, 161 Drug Resistance, 65, 161 Drug Tolerance, 161, 210 Duct, 142, 161, 190, 203 Ductus Arteriosus, 28, 32, 35, 37, 38, 40, 41, 44, 45, 46, 47, 49, 51, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 66, 68, 78, 110, 161, 190 Duodenum, 146, 161, 162, 168, 191, 207 Dyes, 142, 146, 161, 167 Dysgenesis, 63, 161 Dysmenorrhea, 161, 193 Dyspepsia, 90, 161 Dysplasia, 13, 26, 161 E Ectopic, 20, 161 Edema, 49, 156, 161, 167, 176, 186

Efficacy, 17, 19, 38, 39, 42, 63, 161 Eicosanoids, 5, 10, 11, 12, 21, 161 Elasticity, 43, 162 Elastin, 154, 162, 165 Electrode, 65, 162 Electrolyte, 21, 141, 157, 162, 195, 206 Electrons, 144, 146, 162, 177, 189, 200 Emboli, 162, 215 Embolism, 162, 199, 215 Embolization, 162, 215 Embolus, 162, 175 Embryo, 142, 147, 151, 162, 166, 175, 215 Emesis, 90, 136, 162 Emollient, 162, 169, 188 Enalapril, 39, 162 Encapsulated, 42, 162 Endocarditis, 149, 162 Endocrine System, 162, 186 Endometrium, 158, 162 Endoscope, 162 Endoscopic, 44, 162 Endothelial cell, 23, 40, 47, 91, 93, 102, 148, 162 Endothelium, 23, 91, 163, 187 Endothelium, Lymphatic, 163 Endothelium, Vascular, 163 Endothelium-derived, 163, 187 Endotoxemia, 23, 163 Endotoxin, 7, 23, 163, 212 Enhancer, 36, 92, 163 Enteritis, 44, 163 Enterocolitis, 26, 56, 163 Enterocytes, 6, 163 Enterohepatic, 163, 208 Enterohepatic Circulation, 163, 208 Entorhinal Cortex, 107, 163, 172 Enuresis, 46, 163 Environmental Health, 120, 122, 163 Enzymatic, 8, 19, 149, 155, 163, 172 Enzyme, 12, 18, 19, 21, 22, 27, 59, 106, 107, 144, 145, 150, 154, 162, 163, 170, 172, 174, 179, 182, 189, 191, 192, 194, 197, 200, 201, 202, 203, 205, 208, 210, 211, 214, 215 Eosinophilic, 42, 50, 163 Eosinophils, 48, 163, 170, 178 Epidermal, 91, 163, 182 Epidermal Growth Factor, 91, 163 Epidermis, 163, 164, 199 Epidermoid carcinoma, 164, 206, 207 Epinephrine, 140, 160, 164, 187, 212 Episcleritis, 15, 164, 204

222

Indomethacin

Episiotomy, 41, 164 Epithelial, 6, 13, 14, 21, 37, 61, 139, 153, 158, 164, 170, 171, 178, 190 Epithelial Cells, 6, 13, 14, 21, 37, 61, 164, 171, 178 Epithelium, 13, 21, 22, 146, 163, 164, 168, 177 Erectile, 164, 191 Erection, 164, 193 Erythema, 69, 156, 164, 208 Erythrocytes, 93, 148, 164, 201, 205 Esophageal, 53, 164 Esophagitis, 102, 164 Esophagus, 89, 160, 164, 188, 191, 192, 201, 207 Estradiol, 67, 164 Estrogens, 164, 170 Ethanol, 7, 72, 164 Evacuation, 156, 164, 168 Excipient, 86, 165 Excitability, 165, 185, 199 Excitation, 142, 165, 166 Exogenous, 25, 147, 150, 165, 212 Expiration, 165, 202 Extensor, 165, 198 External-beam radiation, 165, 177, 200, 215 Extracellular, 15, 18, 91, 93, 142, 156, 165, 166, 181, 184, 206 Extracellular Matrix, 15, 91, 156, 165, 166, 181 Extracellular Matrix Proteins, 15, 165, 181 Extracellular Space, 165 Extraction, 19, 65, 152, 165 Extrapyramidal, 161, 165 Extravasation, 20, 165 Extremity, 165, 190, 204 F Family Planning, 121, 165 Fat, 145, 147, 148, 157, 162, 165, 179, 203, 209, 212 Fatigue, 104, 165, 171 Fatty acids, 28, 141, 161, 165, 169, 179, 181, 197, 210 Feces, 156, 165, 207 Femur, 50, 165 Fetal Blood, 11, 161, 166 Fetal Membranes, 11, 55, 166 Fetus, 28, 39, 152, 166, 181, 193, 196, 213 Fibrin, 13, 148, 166, 191, 210 Fibrinogen, 166, 194, 210 Fibroblasts, 56, 102, 166

Fibronectins, 165, 166 Fibrosis, 7, 166 Filtration, 23, 166 Fixation, 166, 205 Flatulence, 90, 166 Flatus, 166, 168 Flow Cytometry, 11, 166 Fluorescence, 12, 14, 166, 167 Fluorescent Dyes, 166, 167 Fluorouracil, 50, 62, 77, 167 Fluoxetine, 40, 167 Flurbiprofen, 87, 98, 167 Flushing, 94, 95, 167 Fold, 8, 10, 46, 167, 182 Follicles, 167 Folliculitis, 42, 167 Forearm, 148, 167 Fractionation, 84, 167 Functional magnetic resonance imaging, 25, 167 Fundus, 14, 167 Fungi, 85, 93, 143, 156, 167, 176, 183, 215 Fungus, 149, 167 Furosemide, 31, 44, 167 G Gallate, 84, 168 Gallbladder, 139, 147, 160, 167, 168 Gamma Rays, 168, 200 Ganglia, 139, 168, 186, 191 Gas, 20, 150, 159, 166, 168, 173, 187, 208, 214 Gas exchange, 168, 214 Gastric, 14, 36, 37, 48, 66, 67, 72, 84, 90, 97, 98, 141, 161, 163, 168, 172, 191 Gastric Emptying, 90, 168 Gastric Fundus, 14, 72, 168 Gastric Juices, 168, 191 Gastric Mucosa, 14, 67, 98, 168 Gastrin, 14, 168, 172 Gastritis, 57, 168 Gastrointestinal, 4, 8, 12, 44, 56, 85, 90, 98, 112, 148, 164, 166, 168, 178, 193, 205, 208, 212 Gastrointestinal tract, 85, 98, 99, 164, 166, 168, 178, 205, 212 Gelatin, 82, 88, 100, 103, 168, 208 Gels, 100, 168 Gene, 6, 8, 16, 19, 23, 24, 101, 106, 147, 168, 188, 194, 201, 211 Gene Expression, 6, 16, 23, 101, 168 Genetic Engineering, 147, 154, 168 Genetics, 28, 156, 168, 176

Index 223

Genital, 11, 168 Genotype, 13, 168, 192 Gestation, 11, 17, 26, 28, 169, 191, 193 Gestational, 17, 169 Gestational Age, 17, 169 Giardiasis, 169, 183, 199 Gland, 106, 140, 157, 169, 180, 190, 193, 197, 204, 207, 208, 210 Glioblastoma, 34, 169 Globus Pallidus, 169, 199 Glomerular, 10, 38, 169, 202 Glomeruli, 10, 169, 199 Glomerulosclerosis, 10, 169 Glomerulus, 169, 186 Glucocorticoid, 9, 159, 169, 195, 196 Glucose, 48, 145, 148, 151, 159, 169, 171, 175, 176, 201, 203 Glucuronic Acid, 169, 171 Glycerol, 169, 193 Glycerophospholipids, 169, 193 Glycoprotein, 166, 170, 178, 212 Glycosaminoglycans, 165, 170 Goblet Cells, 163, 170 Gonadal, 170, 207 Gonadotropin, 13, 170 Gout, 42, 92, 110, 126, 154, 170, 208 Governing Board, 170, 195 Graft, 15, 170, 172, 174 Graft Rejection, 170, 174 Gram-negative, 151, 163, 170 Granulocytes, 170, 205, 215 Growth factors, 26, 170 Guanfacine, 82, 170 Guanylate Cyclase, 170, 187 Guinea Pigs, 27, 170 H Haematemesis, 162, 170 Hair follicles, 167, 170 Half-Life, 170, 193 Haloperidol, 3, 170 Haptens, 140, 171 Headache, 32, 35, 36, 38, 42, 44, 45, 55, 58, 65, 106, 110, 111, 136, 149, 171, 172, 175 Headache Disorders, 106, 171 Heart attack, 150, 171 Heart failure, 64, 171, 179 Heme, 147, 158, 171, 189, 195 Hemicrania, 32, 38, 44, 45, 55, 65, 106, 171 Hemodynamics, 37, 61, 171 Hemoglobin, 164, 171, 195 Hemorrhage, 17, 24, 29, 33, 52, 58, 64, 68, 78, 157, 171, 207

Hemostasis, 171, 205 Heparin, 59, 171 Hepatic, 23, 85, 141, 171, 179 Hepatitis, 7, 66, 171 Hepatocellular, 23, 171 Hepatocytes, 171 Hereditary, 43, 170, 171, 192 Heredity, 168, 172 Herpes, 96, 172 Herpes virus, 96, 172 Herpes Zoster, 96, 172 Heterogeneity, 140, 172 Heterotrophic, 167, 172 Hippocampus, 107, 158, 172, 179, 208 Histamine, 14, 172 Histidine, 87, 172 Homeostasis, 8, 14, 90, 172 Homodimer, 172, 211 Homologous, 172, 205, 209 Hormone, 48, 90, 140, 141, 157, 162, 164, 168, 172, 176, 182, 186, 189, 196, 203, 205, 209, 210, 211 Hormone therapy, 140, 172 Horseradish Peroxidase, 8, 172 Host, 15, 106, 146, 149, 172, 174, 178, 214 Hydrocephalus, 172, 176, 177 Hydrogen, 28, 139, 142, 146, 150, 159, 165, 172, 173, 179, 184, 187, 189, 192, 198, 208 Hydrogen Peroxide, 150, 173, 179, 208 Hydrolysis, 147, 151, 153, 173, 192, 195 Hydrophilic, 82, 173 Hydrophobic, 169, 173, 179 Hydroxylysine, 154, 173 Hydroxyproline, 154, 173 Hydroxyurea, 95, 173 Hyperaemia, 156, 173 Hyperalgesia, 20, 72, 173 Hypercapnia, 41, 173 Hypersensitivity, 141, 159, 173, 178, 203, 204 Hypertension, 10, 39, 142, 150, 162, 173, 176, 179 Hyperuricemia, 126, 170, 173 Hypesthesia, 173, 186 Hypoglycemia, 54, 59, 173 Hypotension, 72, 156, 173 Hypothalamus, 173, 179, 193 Hypoxia, 26, 173 Hysterotomy, 152, 173 I Id, 73, 127, 132, 134, 173 Idiopathic, 5, 107, 173

224

Indomethacin

Ileal, 64, 174 Ileostomy, 174, 185 Ileum, 53, 151, 174 Immune function, 20, 31, 89, 174, 211 Immune response, 140, 144, 146, 157, 170, 171, 174, 188, 204, 208, 214 Immune system, 9, 93, 105, 147, 174, 178, 180, 213, 215 Immunization, 174, 204 Immunohistochemistry, 11, 174 Immunologic, 27, 152, 169, 174, 200 Immunology, 36, 40, 41, 45, 140, 167, 172, 174, 176, 188 Immunosuppressant, 83, 167, 174 Immunosuppressive, 169, 174, 204 Immunosuppressive Agents, 174, 204 Immunosuppressive therapy, 174 Immunotherapy, 83, 147, 159, 174 Impairment, 91, 107, 110, 174, 182, 196, 198 Implant radiation, 174, 176, 177, 200, 215 In vitro, 5, 6, 18, 36, 37, 40, 41, 46, 47, 56, 89, 174, 210 In vivo, 5, 6, 15, 18, 22, 25, 26, 30, 36, 41, 72, 89, 171, 174, 208, 210 Incision, 164, 173, 174, 176 Incubation, 10, 174 Indicative, 174, 190, 213 Induction, 5, 7, 24, 25, 68, 101, 102, 175, 200 Infancy, 175 Infantile, 52, 175 Infarction, 75, 172, 175, 202 Infection, 11, 15, 102, 142, 147, 149, 152, 153, 169, 174, 175, 180, 199, 203, 207, 211, 215 Infiltration, 15, 175, 196 Influenza, 85, 175 Informed Consent, 17, 175 Infuse, 11, 175 Infusion, 11, 27, 175 Initiation, 8, 175, 211 Inner ear, 175, 190 Innervation, 29, 91, 175, 192, 204, 210 Inorganic, 88, 153, 175, 184 Inositol, 29, 175 Inotropic, 161, 175 Insight, 11, 24, 175 Insulin, 48, 176, 203, 212 Insulin-dependent diabetes mellitus, 176 Interferon, 30, 62, 77, 103, 176 Interferon-alpha, 176

Intermediate Filaments, 176, 207 Internal radiation, 176, 177, 200, 215 Interstitial, 148, 165, 176, 177, 186, 202, 215 Intestinal, 6, 36, 57, 67, 85, 94, 97, 98, 99, 163, 176, 181, 190, 215 Intestinal Flora, 85, 176 Intestine, 99, 147, 148, 155, 163, 176, 178, 199 Intoxication, 176, 215 Intracellular, 14, 19, 50, 149, 175, 176, 182, 187, 195, 197, 201, 205, 214 Intracellular Membranes, 176, 182 Intracranial Hypertension, 51, 171, 172, 176 Intracranial Pressure, 53, 66, 176, 198 Intramuscular, 176, 190 Intraperitoneal, 60, 176 Intravenous, 18, 32, 54, 60, 105, 175, 176, 190 Intrinsic, 28, 140, 146, 176 Invasive, 43, 59, 83, 93, 176, 180 Investigative Techniques, 11, 176 Involuntary, 163, 177, 185, 193 Ionization, 177 Ionizing, 50, 53, 101, 102, 141, 177, 200 Ions, 146, 153, 160, 162, 173, 177, 198 Ipsilateral, 20, 177 Iris, 143, 145, 153, 156, 177, 199, 213 Irradiation, 48, 101, 102, 177, 215 Irrigation, 91, 177 Ischemia, 25, 47, 177, 202 Isoelectric, 88, 177 Isoelectric Point, 88, 177 Isosorbide, 82, 177 Isosorbide Dinitrate, 82, 177 J Joint, 45, 48, 59, 92, 98, 106, 126, 145, 177, 189, 209 K Kb, 120, 177 Keratoconjunctivitis, 87, 177 Keto, 75, 177 Ketoconazole, 101, 177 Ketoprofen, 98, 178 Ketorolac, 63, 178 Kidney stone, 178, 202, 213 Kinetic, 177, 178 L Labile, 9, 155, 178 Lacerations, 164, 178 Lactation, 178, 189 Laminin, 13, 15, 146, 165, 178

Index 225

Large Intestine, 97, 98, 151, 155, 160, 176, 178, 201, 206 Latent, 30, 93, 178, 195 Lectin, 178, 182 Lens, 144, 150, 178 Lesion, 5, 96, 178, 180, 212 Lethal, 85, 146, 178 Leukemia, 50, 178 Leukocytes, 11, 15, 30, 146, 148, 152, 163, 170, 175, 176, 178, 184, 192, 212 Leukotrienes, 49, 145, 162, 178, 179 Library Services, 132, 178 Lidocaine, 41, 178 Life cycle, 167, 178 Ligament, 178, 197 Ligands, 22, 179 Ligation, 56, 58, 179 Limbic, 142, 179 Limbic System, 142, 179 Linkage, 9, 151, 179 Lipid, 7, 9, 12, 52, 72, 144, 152, 153, 169, 176, 177, 179, 189 Lipid Peroxidation, 7, 9, 179, 189 Lipofuscin, 93, 152, 179 Lipophilic, 20, 179 Lipopolysaccharide, 31, 93, 170, 179 Lipoprotein, 23, 94, 95, 170, 179, 180 Lipoxygenase, 95, 101, 145, 178, 179 Lipoxygenase Inhibitors, 101, 179 Lisinopril, 39, 179 Lithium, 113, 179 Liver, 7, 8, 23, 31, 139, 141, 145, 146, 147, 160, 163, 165, 168, 169, 171, 179, 180, 196, 200, 202, 214 Liver Cirrhosis, 23, 179 Liver Neoplasms, 179, 214 Lobe, 21, 180 Localization, 11, 47, 174, 180 Localized, 48, 83, 162, 166, 175, 178, 180, 193, 212 Locomotion, 180, 193 Locomotor, 27, 180 Low-density lipoprotein, 179, 180 Lucida, 178, 180 Lumbar, 180, 204, 210 Lung volume, 21, 180 Lupus, 93, 126, 154, 180 Lymph, 50, 152, 153, 162, 163, 180, 208 Lymph node, 152, 180 Lymphadenopathy, 50, 180 Lymphatic, 163, 175, 180, 182, 194, 206 Lymphatic system, 180, 206

Lymphocyte, 144, 180, 181 Lymphoid, 143, 180 Lymphoma, 34, 180 Lysine, 40, 87, 173, 180 M Magnetic Resonance Imaging, 25, 41, 56, 180 Malformation, 36, 180 Malignant, 13, 44, 61, 83, 93, 139, 144, 169, 181, 185, 199, 200, 209 Malignant tumor, 83, 93, 181 Malnutrition, 141, 181 Mammary, 61, 181 Mania, 90, 181 Manic, 113, 179, 181, 199 Manic-depressive psychosis, 181, 199 Manifest, 86, 181 Mastication, 181, 212 Mastocytosis, 18, 181 Matrix metalloproteinase, 11, 55, 181 Mechanical ventilation, 21, 26, 149, 181 Meconium, 47, 181 Mediate, 13, 19, 161, 181 Mediator, 30, 102, 181, 205 Medical Records, 181, 203 Medical Staff, 161, 181 Medicament, 88, 89, 181, 208 MEDLINE, 121, 181 Medullary, 181, 199 Meiosis, 181, 209 Melanin, 177, 181, 192, 212 Melanocytes, 182 Melanoma, 83, 182 Membrane Glycoproteins, 12, 182 Membrane Proteins, 19, 182 Memory, 9, 21, 143, 158, 182 Meninges, 152, 157, 182 Menstruation, 158, 161, 182 Mental Disorders, 79, 182, 198 Mental Processes, 160, 182, 198 Mercury, 65, 166, 182 Mesenchymal, 164, 182 Mesenteric, 35, 41, 182 Mesentery, 182, 191 Meta-Analysis, 60, 182 Metabolic disorder, 159, 170, 182 Metabolite, 6, 12, 147, 182, 196, 200 Metalloporphyrins, 28, 182 Metastasis, 181, 182 Methionine, 183, 208 Metronidazole, 94, 183 MI, 95, 136, 183

226

Indomethacin

Micelle, 98, 183 Microbe, 183, 211 Microbiology, 22, 139, 183 Microcirculation, 23, 53, 179, 183 Microfilaments, 176, 183, 207 Microorganism, 94, 183, 190, 214 Microscopy, 15, 146, 172, 183 Microspheres, 72, 183 Migration, 15, 21, 26, 91, 183 Millimeter, 99, 183 Minocycline, 67, 183 Mitochondrial Swelling, 183, 185 Mitogen-Activated Protein Kinase Kinases, 183 Mitogen-Activated Protein Kinases, 67, 183 Mitosis, 144, 184 Mitotic, 160, 184 Mitotic inhibitors, 160, 184 Modification, 28, 30, 40, 168, 184, 199 Monitor, 6, 184, 187 Monoclonal, 177, 184, 200, 215 Monocytes, 15, 19, 93, 102, 178, 184 Mononuclear, 39, 47, 184, 212 Monophosphate, 8, 21, 184 Mood Disorders, 113, 184 Morphine, 62, 184, 185, 188 Morphological, 6, 162, 167, 182, 184 Morphology, 29, 151, 184 Motility, 64, 112, 175, 184, 205 Motion Sickness, 184, 185 Mucilaginous, 181, 184 Mucins, 163, 170, 184 Mucosa, 14, 98, 163, 168, 180, 184, 215 Mucositis, 101, 184 Mucus, 184, 212 Mutagenesis, 12, 24, 185 Mutagens, 185 Myalgia, 175, 185 Myocardial infarction, 157, 160, 183, 185, 215 Myocardial Ischemia, 143, 185 Myocardium, 143, 183, 185 Myosin, 185, 207, 212 N Narcosis, 185 Narcotic, 33, 184, 185 Nasal Mucosa, 175, 185 Nausea, 8, 90, 136, 161, 185, 198, 212 NCI, 1, 77, 79, 119, 153, 185 Necrosis, 50, 75, 101, 102, 144, 169, 175, 183, 185, 202

Necrotizing Enterocolitis, 17, 26, 52, 57, 110, 185 Need, 3, 6, 17, 26, 33, 37, 66, 90, 112, 128, 140, 153, 181, 185, 210 Neonatal, 11, 17, 25, 29, 38, 57, 58, 60, 61, 63, 185 Neonatal period, 29, 185 Neoplasia, 43, 53, 185, 186 Neoplasm, 13, 185, 186 Neoplastic, 13, 83, 180, 186, 201 Neostriatum, 186, 199 Nephritis, 69, 186 Nephrogenic, 112, 186 Nephrosis, 186 Nephrotic, 10, 186 Nephrotic Syndrome, 10, 186 Nerve Endings, 146, 186 Nerve Fibers, 146, 186, 210 Nervous System, 15, 90, 92, 93, 102, 107, 139, 140, 142, 149, 152, 154, 168, 169, 170, 178, 181, 184, 186, 188, 191, 205, 208, 209 Networks, 93, 186 Neural, 21, 92, 93, 140, 142, 186 Neuritis, 20, 186 Neuroendocrine, 20, 93, 186 Neurologic, 169, 172, 186 Neuronal, 15, 26, 90, 93, 185, 186, 204 Neurons, 21, 154, 158, 159, 168, 186, 187, 209 Neurotoxic, 6, 186 Neurotoxicity, 21, 186 Neurotoxins, 15, 186 Neurotransmitters, 184, 186 Neutrons, 141, 177, 187, 200 Neutrophil, 45, 69, 187 Neutrophil Activation, 45, 187 Niacin, 18, 94, 187, 212 Nicotine, 82, 187 Nitric Oxide, 20, 23, 25, 26, 72, 111, 187 Nitrogen, 141, 142, 165, 166, 182, 187, 212 Nitroglycerin, 82, 177, 187 Norepinephrine, 29, 140, 160, 187 NSAIDs, 8, 12, 19, 22, 27, 93, 95, 98, 105, 187 Nuclear, 16, 18, 22, 25, 47, 146, 156, 162, 168, 169, 179, 185, 187, 200 Nuclei, 21, 141, 142, 156, 162, 168, 179, 180, 184, 187, 188, 198 Nucleic acid, 185, 187, 188, 214 Nursing Care, 188, 191

Index 227

O Ocular, 15, 91, 188 Oesophagitis, 90, 188 Ointments, 87, 161, 188 Oncogene, 67, 188, 201 Opacity, 150, 158, 188 Ophthalmic, 36, 87, 91, 100, 116, 188 Opium, 184, 188 Optic Nerve, 188, 198, 203, 204 Organ Culture, 188, 210 Organ Specificity, 6, 188 Organelles, 158, 182, 184, 188 Osmolality, 46, 188 Osmoles, 188 Osmosis, 188, 189 Osmotic, 21, 141, 177, 183, 188, 189, 205 Ossification, 45, 48, 49, 52, 59, 60, 189 Osteoarthritis, 98, 178, 189, 193 Outpatient, 7, 189 Ovary, 164, 189 Overdose, 46, 135, 189 Overexpress, 16, 189 Ovulation, 13, 189 Ovum, 158, 169, 178, 189, 196 Oxidation, 19, 139, 144, 145, 147, 157, 158, 179, 189 Oxidation-Reduction, 147, 189 Oxidative metabolism, 55, 140, 178, 189 Oxidative Stress, 7, 72, 189 Oxygen Consumption, 189, 202 Oxygenase, 34, 89, 90, 189 Oxygenation, 28, 56, 189 Oxytocin, 21, 189 P Palliative, 9, 190, 210 Palliative therapy, 9, 190 Palsy, 11, 190 Pancreas, 139, 147, 160, 176, 190, 212 Paneth Cells, 163, 190 Par excellence, 9, 190 Parenchyma, 15, 85, 190 Parenteral, 58, 103, 110, 190 Paresis, 186, 190 Paresthesias, 186, 190 Paroxysmal, 32, 38, 106, 143, 171, 190 Partial remission, 190, 202 Particle, 183, 190, 211, 214 Patch, 190, 211 Pathogen, 14, 174, 190 Pathogenesis, 8, 16, 21, 94, 190 Pathologic, 144, 147, 149, 157, 173, 190, 198, 202

Pathologic Processes, 144, 190 Pathophysiology, 4, 5, 11, 190 Patient Care Management, 112, 190 Patient Compliance, 95, 191 Patient Education, 126, 130, 132, 136, 191 Pelvic, 191, 197 Penis, 96, 191 Pepsin, 191 Peptic, 90, 191 Peptic Ulcer, 90, 191 Peptide, 27, 44, 103, 191, 195, 198, 201 Percutaneous, 104, 191 Perforation, 57, 191 Perfusion, 173, 191 Perinatal, 29, 44, 56, 57, 58, 60, 62, 63, 66, 191 Periodontal disease, 167, 191 Peripheral blood, 15, 90, 176, 191 Peripheral Nervous System, 190, 191, 208 Peritoneal, 60, 90, 176, 191 Peritoneal Cavity, 176, 191 Peritoneum, 182, 191 Peritonitis, 98, 191 Perivascular, 29, 192 Peroneal Nerve, 192, 204 Peroxidase, 8, 28, 145, 179, 192 Peroxide, 16, 192 PH, 35, 48, 96, 192 Phagocytosis, 45, 192 Pharmaceutical Preparations, 64, 89, 152, 164, 168, 192, 196 Pharmaceutical Solutions, 161, 192 Pharmacist, 88, 192 Pharmacodynamics, 38, 192 Pharmacokinetic, 192 Pharmacologic, 143, 146, 170, 192, 211 Pharmacotherapy, 3, 9, 35, 192 Pharynx, 175, 192 Phenolphthalein, 105, 192 Phenotype, 13, 16, 19, 192 Phenyl, 96, 192 Phenylalanine, 192, 212 Phenylbutyrate, 62, 77, 192 Phospholipases, 192, 205 Phospholipids, 18, 165, 175, 179, 193, 197 Phosphorus, 149, 193 Phosphorylated, 62, 154, 183, 193 Phosphorylation, 13, 48, 183, 193, 198 Physical Examination, 4, 126, 169, 193 Physiologic, 91, 141, 147, 170, 182, 193, 197, 201, 202

228

Indomethacin

Physiology, 13, 21, 22, 25, 28, 34, 44, 48, 72, 193 Pigment, 147, 152, 179, 182, 193 Piloerection, 27, 193 Pilot study, 58, 193 Piroxicam, 89, 98, 193 Pituitary Gland, 21, 157, 193 Placenta, 28, 164, 166, 193, 196 Plague, 12, 193 Plant Components, 5, 193 Plants, 141, 150, 151, 153, 154, 169, 178, 184, 186, 187, 193, 203, 211 Plaque, 19, 145, 193 Plasma protein, 141, 163, 194, 198, 205 Plasticity, 21, 27, 194 Platelet Activation, 194, 205 Platelet Aggregation, 42, 93, 187, 194, 210 Platelets, 145, 187, 194, 210 Platinum, 50, 153, 194 Plexus, 194, 204 Pneumonitis, 102, 194 Poisoning, 176, 182, 185, 194 Polyarthritis, 5, 194 Polyethylene, 82, 194 Polyhydramnios, 51, 194 Polymers, 82, 93, 194, 198 Polymorphic, 12, 36, 159, 194 Polymorphism, 104, 194 Polypeptide, 102, 154, 163, 166, 195 Polyposis, 58, 111, 155, 195 Polysaccharide, 144, 151, 195, 198 Porphyrins, 182, 195 Posterior, 21, 91, 145, 161, 164, 177, 189, 190, 195, 204, 206 Postnatal, 26, 28, 195, 207 Postoperative, 11, 33, 53, 59, 62, 193, 195 Postsynaptic, 195, 205, 209 Post-traumatic, 171, 195 Potassium, 74, 141, 195, 199 Potentiate, 85, 195 Potentiation, 195, 205 Practice Guidelines, 122, 195 Precancerous, 152, 195 Precipitating Factors, 171, 195 Precursor, 19, 108, 145, 153, 160, 163, 187, 192, 195, 196, 198, 211, 212 Predisposition, 13, 23, 195 Prednisolone, 9, 16, 97, 195, 196 Prednisone, 4, 196 Pregnancy Tests, 169, 196 Pregnenolone, 93, 196 Prenatal, 39, 63, 162, 196

Prevalence, 107, 196 Primary endpoint, 17, 196 Probenecid, 31, 92, 126, 196 Procaine, 178, 196 Prodrug, 9, 196, 200 Progeny, 156, 196 Progesterone, 196, 207 Progression, 7, 10, 143, 196 Progressive, 5, 10, 151, 153, 158, 161, 170, 185, 189, 194, 196, 202 Projection, 187, 188, 196 Proline, 154, 173, 196 Prone, 13, 196 Prophase, 196, 209 Prophylaxis, 45, 46, 49, 51, 55, 60, 65, 78, 89, 196, 215 Proportional, 188, 196 Propylene Glycol, 101, 196 Prospective study, 66, 196 Prostaglandins A, 25, 174, 197 Prostaglandins D, 24, 197 Prostaglandins F, 197 Prostate, 109, 147, 197, 212 Protein C, 141, 144, 146, 179, 197, 212 Protein Kinase C, 183, 197 Protein S, 147, 197, 210 Protein-Serine-Threonine Kinases, 183, 198 Proteinuria, 10, 169, 186, 198 Proteoglycans, 146, 165, 198 Prothrombin, 198, 210 Protons, 141, 173, 177, 198, 200 Protozoa, 93, 156, 183, 198 Proximal, 106, 160, 198 Pseudomembranous Colitis, 94, 198 Pseudotumor Cerebri, 176, 198 Psoriasis, 9, 113, 198 Psychiatric, 61, 113, 182, 198 Psychiatry, 20, 40, 166, 198, 207, 214 Psychology, 27, 160, 198 Psychosis, 3, 50, 53, 169, 198 Public Policy, 121, 199 Publishing, 30, 199 Pulmonary, 28, 37, 148, 149, 161, 163, 178, 190, 199, 214, 215 Pulmonary Artery, 148, 161, 190, 199, 214 Pulmonary Circulation, 28, 199 Pulmonary Embolism, 199, 215 Pulse, 184, 199 Pupil, 153, 156, 160, 199 Pustular, 42, 199 Putamen, 5, 186, 199

Index 229

Pyelonephritis, 30, 199 Pylorus, 84, 199 Q Quality of Life, 190, 199 Quinacrine, 113, 199 Quinidine, 113, 199 Quinine, 199 R Race, 183, 200 Radiation, 24, 50, 52, 53, 59, 83, 93, 101, 102, 140, 143, 165, 167, 168, 176, 177, 183, 200, 208, 215 Radiation therapy, 52, 59, 140, 165, 167, 176, 177, 200, 215 Radioactive, 93, 170, 173, 174, 176, 177, 187, 200, 212, 215 Radioactivity, 18, 200 Radiography, 169, 200 Radiolabeled, 177, 200, 215 Radiological, 191, 200 Radiosensitization, 16, 50, 53, 200 Radiotherapy, 148, 177, 200, 215 Ramipril, 38, 200 Random Allocation, 200 Randomization, 17, 200 Randomized, 17, 24, 32, 34, 42, 49, 57, 60, 61, 78, 161, 200 Randomized clinical trial, 17, 200 Ras gene, 201 Ras Proteins, 13, 201 Reabsorption, 163, 196, 201 Reactive Oxygen Species, 21, 201 Reality Testing, 198, 201 Receptor, 5, 12, 18, 19, 20, 21, 22, 26, 28, 29, 33, 36, 91, 139, 144, 155, 161, 197, 201, 205 Receptors, Serotonin, 201, 205 Recombinant, 83, 201, 213 Recombination, 156, 201 Reconstitution, 28, 201 Rectal, 17, 33, 49, 58, 62, 77, 97, 104, 111, 201 Rectovaginal Fistula, 53, 201 Rectum, 53, 77, 97, 144, 148, 155, 160, 166, 168, 178, 197, 201, 208 Red blood cells, 164, 189, 201, 203 Reductase, 8, 31, 201 Refer, 1, 149, 155, 166, 167, 172, 180, 187, 198, 201 Reflux, 90, 112, 201 Regeneration, 20, 201 Regimen, 4, 87, 161, 191, 192, 201

Regurgitation, 69, 202 Relapse, 94, 202 Remission, 106, 181, 202 Renal failure, 10, 202 Renal tubular, 63, 196, 202 Renin, 150, 202 Renin-Angiotensin System, 150, 202 Reperfusion, 25, 202 Reperfusion Injury, 202 Resorption, 167, 172, 201, 202 Respiration, 21, 150, 166, 184, 202 Respirator, 181, 202, 214 Respiratory distress syndrome, 17, 38, 40, 61, 102, 149, 202 Respiratory Physiology, 202, 213 Restitution, 48, 202 Restoration, 201, 202, 215 Retina, 91, 153, 178, 188, 203, 213 Retinopathy, 46, 49, 203 Retrospective, 33, 57, 203 Retrospective study, 33, 203 Rheumatism, 42, 173, 203 Rheumatoid, 9, 84, 98, 107, 154, 178, 193, 203 Rheumatoid arthritis, 9, 84, 98, 107, 154, 178, 193, 203 Ribonucleoside Diphosphate Reductase, 173, 203 Rigidity, 176, 193, 203 Risk factor, 196, 203 Rod, 146, 163, 203 Rosiglitazone, 22, 203 S Salicylate, 103, 203, 206 Salicylic, 97, 104, 203 Salivary, 160, 203, 208 Salivary glands, 160, 203 Saponins, 203, 207 Schizoid, 203, 215 Schizophrenia, 90, 203, 215 Schizotypal Personality Disorder, 203, 215 Sciatic Nerve, 20, 192, 204, 210 Sclera, 15, 153, 156, 164, 204, 213 Scleritis, 15, 204 Screening, 7, 154, 204 Second cancer, 22, 204 Secretion, 14, 19, 21, 48, 67, 84, 93, 94, 157, 163, 172, 176, 178, 184, 204, 211 Secretory, 14, 92, 94, 204, 209 Segmental, 10, 169, 204 Segmentation, 204 Seizures, 169, 190, 204

230

Indomethacin

Sella, 193, 204 Semen, 197, 204 Semisynthetic, 151, 183, 204 Senescence, 9, 204 Senile, 18, 204 Senile Plaques, 18, 204 Sensibility, 142, 173, 204 Sensitization, 20, 23, 204 Sensor, 29, 205 Serotonin, 29, 167, 192, 201, 205, 208, 212 Serous, 163, 205 Serum, 13, 40, 46, 56, 65, 95, 102, 110, 141, 155, 170, 180, 191, 201, 205, 208, 212 Serum Albumin, 40, 56, 205 Shock, 16, 47, 50, 163, 205, 211 Shunt, 28, 205 Side effect, 8, 12, 17, 32, 34, 61, 83, 85, 86, 92, 95, 115, 140, 147, 173, 193, 205, 208, 211 Signal Transduction, 12, 19, 102, 175, 205 Signs and Symptoms, 202, 205 Skeletal, 87, 199, 205, 212 Skeleton, 139, 165, 177, 197, 205 Skull, 157, 176, 190, 205, 209 Small intestine, 6, 97, 98, 147, 151, 153, 161, 163, 169, 172, 174, 176, 205, 214 Smooth muscle, 23, 26, 29, 72, 142, 146, 149, 172, 184, 187, 197, 202, 206, 208 Socialization, 25, 206 Sodium, 89, 93, 141, 159, 170, 199, 201, 206 Sodium salicylate, 93, 206 Solvent, 88, 164, 169, 188, 189, 192, 196, 206 Somatic, 179, 181, 184, 191, 206, 209 Specialist, 127, 160, 206 Specificity, 6, 12, 140, 145, 206 Spectrum, 177, 206 Sphenoid, 190, 204, 206 Spinal cord, 59, 92, 93, 145, 152, 153, 182, 186, 191, 204, 206 Spirochete, 206, 209 Spleen, 31, 180, 206 Squamous, 24, 46, 164, 206, 207 Squamous cell carcinoma, 24, 46, 164, 206 Squamous cells, 206, 207 Stabilization, 11, 16, 62, 207 Stabilizer, 16, 207 Staphylococcus, 183, 207 Stasis, 90, 207 Stem Cells, 102, 207 Sterile, 87, 207

Steroid, 4, 9, 11, 93, 99, 147, 157, 196, 203, 207 Stimulant, 149, 160, 172, 207 Stimulus, 156, 162, 165, 175, 190, 207, 210 Stomach, 86, 97, 98, 106, 136, 139, 160, 164, 167, 168, 172, 185, 191, 192, 199, 201, 205, 206, 207 Stool, 178, 207 Stress, 23, 27, 48, 150, 151, 157, 167, 184, 185, 189, 195, 203, 207 Stress Fibers, 48, 207 Stroke, 49, 78, 79, 120, 150, 207 Stroma, 91, 177, 190, 207 Stupor, 185, 207 Subacute, 30, 102, 175, 207 Subarachnoid, 171, 207 Subclinical, 175, 204, 207 Subcutaneous, 5, 161, 190, 208 Subiculum, 172, 208 Submaxillary, 163, 208 Subspecies, 206, 208 Substance P, 88, 182, 201, 204, 208 Substrate, 8, 12, 26, 28, 179, 208 Suction, 166, 208 Sulfinpyrazone, 126, 208 Sulfur, 96, 165, 183, 208 Sulindac, 32, 85, 98, 208 Sumatriptan, 42, 208 Sunburn, 102, 208 Superoxide, 103, 208 Superoxide Dismutase, 103, 208 Suppositories, 17, 33, 97, 104, 111, 168, 208 Suppression, 31, 63, 157, 208 Suppressive, 9, 208 Suspensions, 87, 208 Sympathomimetic, 161, 164, 187, 208 Symphysis, 197, 209 Symptomatic, 44, 55, 209 Symptomatology, 27, 209 Synapsis, 209 Synaptic, 15, 187, 205, 209 Synaptic Transmission, 187, 209 Synergistic, 9, 12, 65, 209 Synovial, 55, 209 Synovial Fluid, 55, 209 Synovial Membrane, 209 Syphilis, 31, 209 Systemic, 9, 18, 27, 29, 83, 99, 103, 104, 116, 144, 148, 149, 154, 164, 171, 175, 176, 177, 195, 200, 204, 209, 215 Systemic disease, 83, 209 Systolic, 170, 173, 209

Index 231

T Tachycardia, 160, 209 Telomerase, 36, 47, 209 Temporal, 11, 20, 142, 171, 172, 190, 209 Temporal Lobe, 142, 209 Terminal disease, 105, 209 Testicular, 72, 209 Testis, 164, 209 Testosterone, 201, 209 Tetracycline, 84, 85, 183, 210 Tetrahydrocannabinol, 149, 210 Therapeutics, 33, 62, 64, 66, 67, 116, 177, 210 Thermal, 50, 160, 187, 210 Thigh, 20, 210 Threshold, 50, 165, 173, 210 Thrombin, 13, 166, 194, 197, 198, 210 Thrombosis, 59, 198, 207, 210 Thromboxanes, 145, 162, 210 Thrombus, 157, 175, 185, 194, 210, 213 Thyroid, 210, 212 Thyroxine, 141, 192, 210 Tibial Nerve, 204, 210 Tin, 194, 210 Tissue Culture, 94, 210 Tocolysis, 17, 52, 57, 61, 66, 69, 110, 111, 210 Tolerance, 5, 68, 139, 210 Tonicity, 87, 210 Tooth Preparation, 139, 211 Topical, 9, 15, 43, 68, 92, 99, 103, 104, 106, 145, 164, 173, 211 Torsion, 175, 211 Toxic, iv, 5, 31, 83, 156, 158, 186, 187, 211 Toxicity, 5, 6, 8, 84, 85, 92, 161, 182, 211, 214 Toxicokinetics, 211 Toxicology, 72, 122, 211 Toxins, 94, 144, 169, 175, 211, 213 Tracer, 172, 211 Transcriptase, 209, 211 Transcription Factors, 16, 19, 22, 211 Transdermal, 82, 104, 211 Transduction, 19, 20, 205, 211 Transfection, 147, 211 Transforming Growth Factor beta, 31, 211 Translational, 29, 211 Translocation, 45, 53, 211 Transmitter, 139, 160, 181, 187, 211 Trauma, 52, 59, 65, 91, 164, 185, 211 Trichomoniasis, 183, 211 Trigeminal, 64, 212

Troglitazone, 22, 212 Tropomyosin, 212 Troponin, 40, 212 Tryptophan, 154, 205, 212 Tuberculosis, 180, 203, 212 Tumor marker, 147, 212 Tumor Necrosis Factor, 83, 90, 101, 102, 212 Tumorigenic, 83, 212 Type 2 diabetes, 48, 212 Tyrosine, 13, 19, 160, 212 U Ulcer, 72, 84, 212 Ulceration, 98, 191, 212 Ulcerative colitis, 9, 212 Ulcerogenic, 14, 212 Ultrasonography, 169, 212 Unconscious, 136, 173, 212 Uremia, 202, 212 Urethra, 191, 197, 212, 213 Uric, 126, 141, 170, 173, 213 Uricosuric, 196, 208, 213 Urinary, 46, 149, 163, 172, 213, 215 Urinate, 96, 213 Urine, 18, 65, 96, 112, 143, 147, 159, 160, 163, 178, 186, 198, 212, 213 Uterine Contraction, 189, 210, 213 Uterus, 152, 157, 158, 162, 167, 173, 182, 196, 213 Uvea, 213 Uveitis, 15, 213 V Vaccine, 140, 213 Vagina, 149, 152, 173, 182, 201, 213 Vaginal, 49, 164, 213 Vaginitis, 149, 213 Vascular, 12, 15, 25, 28, 29, 67, 93, 148, 163, 170, 171, 175, 179, 183, 187, 193, 210, 213 Vasoactive, 26, 29, 213 Vasoconstriction, 24, 160, 164, 213 Vasodilatation, 99, 213 Vasodilation, 24, 213 Vasodilator, 23, 148, 161, 172, 177, 213 Vector, 16, 19, 211, 213 Vein, 59, 143, 145, 176, 187, 213 Venereal, 96, 209, 213 Venoms, 186, 213 Venous, 145, 187, 198, 213, 215 Venous Thrombosis, 213, 215 Ventilation, 22, 213, 214 Ventilator, 181, 202, 214 Ventricle, 107, 142, 172, 173, 199, 209, 214

232

Indomethacin

Venules, 148, 149, 163, 183, 214 Vertebrae, 206, 214 Vesicular, 106, 172, 214 Veterinary Medicine, 89, 121, 214 Villi, 172, 214 Villous, 53, 214 Villus, 6, 214 Vinyl Chloride, 82, 214 Viral, 104, 105, 166, 175, 211, 212, 214 Virulence, 146, 211, 214 Virus, 15, 31, 66, 104, 105, 146, 152, 163, 168, 176, 194, 211, 214 Virus Replication, 66, 214 Viscosity, 87, 100, 214 Visual Acuity, 204, 214 Vitamin A, 175, 214 Vitro, 5, 6, 18, 42, 89, 171, 214 Vivo, 6, 18, 89, 214

W War, 17, 96, 214 Warfarin, 109, 215 White blood cell, 143, 178, 180, 184, 187, 215 Withdrawal, 40, 215 Wound Healing, 181, 215 X Xanthine, 8, 141, 215 Xanthine Oxidase, 141, 215 Xenograft, 143, 215 X-ray, 12, 36, 93, 101, 102, 167, 168, 177, 187, 200, 207, 215 X-ray therapy, 177, 215 Y Yeasts, 149, 167, 176, 192, 215 Yolk Sac, 166, 215 Z Zygote, 155, 156, 215

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