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

HISTAMINES A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET R EFERENC...

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HISTAMINES A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

HISTAMINES 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., 1960Histamines: 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: 0-497-00547-6 1. Histamines-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 histamines. 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 HISTAMINES .............................................................................................. 3 Overview........................................................................................................................................ 3 Federally Funded Research on Histamines .................................................................................... 3 E-Journals: PubMed Central ......................................................................................................... 6 The National Library of Medicine: PubMed .................................................................................. 6 CHAPTER 2. NUTRITION AND HISTAMINES .................................................................................... 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Histamines................................................................................... 23 Federal Resources on Nutrition ................................................................................................... 24 Additional Web Resources ........................................................................................................... 25 CHAPTER 3. PATENTS ON HISTAMINES .......................................................................................... 27 Overview...................................................................................................................................... 27 Patents on Histamines ................................................................................................................. 27 Patent Applications on Histamines ............................................................................................. 42 Keeping Current .......................................................................................................................... 58 CHAPTER 4. BOOKS ON HISTAMINES .............................................................................................. 59 Overview...................................................................................................................................... 59 Book Summaries: Online Booksellers........................................................................................... 59 CHAPTER 5. PERIODICALS AND NEWS ON HISTAMINES ................................................................ 61 Overview...................................................................................................................................... 61 News Services and Press Releases................................................................................................ 61 Academic Periodicals covering Histamines ................................................................................. 63 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 65 Overview...................................................................................................................................... 65 U.S. Pharmacopeia....................................................................................................................... 65 Commercial Databases ................................................................................................................. 69 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 73 Overview...................................................................................................................................... 73 NIH Guidelines............................................................................................................................ 73 NIH Databases............................................................................................................................. 75 Other Commercial Databases....................................................................................................... 77 APPENDIX B. PATIENT RESOURCES ................................................................................................. 79 Overview...................................................................................................................................... 79 Patient Guideline Sources............................................................................................................ 79 Finding Associations.................................................................................................................... 81 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 83 Overview...................................................................................................................................... 83 Preparation................................................................................................................................... 83 Finding a Local Medical Library.................................................................................................. 83 Medical Libraries in the U.S. and Canada ................................................................................... 83 ONLINE GLOSSARIES.................................................................................................................. 89 Online Dictionary Directories ..................................................................................................... 89 HISTAMINES DICTIONARY....................................................................................................... 91 INDEX .............................................................................................................................................. 141

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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 histamines 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 histamines, 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 histamines, 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 histamines. 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 histamines, 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 histamines. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON HISTAMINES Overview In this chapter, we will show you how to locate peer-reviewed references and studies on histamines.

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

Project Title: BCRP REGULATION

IN

PREGNANCY:

ACTIVITY,

EXPRESSION

AND

Principal Investigator & Institution: Mao, Qingcheng; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Histamines

Summary: While the importance of P-glycoprotein (P-gp) in determining drug disposition has been well recognized, the role of Breast Cancer Resistance Protein (BCRP) in this regard has just begun to be realized. Both P-gp and BCRP are expressed in the apical membranes of small intestinal epithelium, the liver canalicular membranes, and the placental syncytiotrophoblasts. Thus, it is not surprising that BCRP, like P-gp, affects the bioavailability and fetal distribution of drugs. Pregnant women are routinely administered various drugs such as antivirals, anti-epileptics, antibiotics, antihypertensives, and anti-histamines. Many of these drugs are substrates or modulators of P-gp. As BCRP and P-gp have considerable degree of substrate overlap, many of these drugs are also likely to be substrates of BCRP. In order to assess if BCRP plays an important role in determining the safety and bioavailability of drugs given during pregnancy, it is critical that we first determine which of the drugs routinely administered to pregnant women are substrates of BCRP. BCRP has the highest expression levels in the placenta where it functions, like P-gp, to protect the fetus from Xenobiotics. Preliminary data from our laboratories indicate that expression of both BCRP and P-gp in the placenta is gestational-age dependent, suggesting regulation by pregnancy-specific hormones. The Hypothesis and Specific Aims outlined below are designed to address these clinically relevant questions. Hypothesis: BCRP and placental P-gp activity and expression is up-regulated during pregnancy and alters the absorption, distribution (including across the placenta), and elimination of drugs BCRP and P-gp substrates) routinely administered to pregnant women. To test the above hypothesis we will determine: 1. If drugs routinely administered to pregnant women (e.g., anti-HIV protease inhibitors, anti-epileptic drugs, antibiotics, ani-hypertensives and antihistamines) are high-affinity substrates of BCRP. 2. If in vitro and in vivo expression of BCRP and P-gp is regulated by pregnancy-specific hormones. 3. The molecular mechanism by which BCRP and P-gp expression is regulated by pregnancyspecific hormones. 4. If the in vivo absorption and fetal distribution of a high-affinity BCRP substrates (routinely administered to pregnant women) is affected y pregnancy in P-gp-deficient mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNDROME

HYPOCRETIN,

HISTAMINE

AND

THE

RESTLESS

LEGS

Principal Investigator & Institution: Allen, Richard P.; Assistant Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Restless Legs Syndrome (RLS) is a common sensorymotor disorders whose symptoms predominant at night and often lead to significant sleep loss and changes in one's quality of life. Rest and transiting between sleep and wake exacerbates RLS symptoms. Accordingly, alerting activities reduce while soporific ones exacerbate the symptoms. Sedating medications such as benzodiazepines, however, do not appear to exacerbate the disorder. RLS when even moderately severe profoundly disturbs sleep, reducing sleep times to 5-6 hours or less. Patients report some daytime problems with alertness and cognitive clarity but despite this reduction in sleep times untreated patients do not describe profound episodes of sleepiness that occur for normal subjects maintained on such restricted sleep schedules. There is apparently some alerting mechanism partially compensating for the sleep loss. Our recent work has found that nocturnal CSF values of hypocretin/orexin (Hcrt) are elevated in RLS patients not currently on treatment. Hcrt is almost absent in narcoleptics and serves to maintain wakefulness operating at least in part through the stimulating

Studies

5

aspects of the histamine system. Several RLS patients on treatment with dopamine agents report some problems with sleepiness they had not previously experienced and several also report marked exacerbation of RLS symptoms by sedating anti-histamines. We have proposed that the Hcrt and histamine system activation reduces RLS symptoms for some RLS patients. DA treatment may reduce the activating benefit from this system leaving the patient vulnerable to sleepiness but also to further exacerbation of the symptoms by further reduction in this system by an anti-histamine medication. Thus, in this model, nocturnal Hcrt levels will be less for DA treated patients and antihistamine challenge provides a test discriminating those patients who have this aspect of RLS, identified in our prior work as those with the familial early-onset form of RLS. The anti-histamine challenge may therefore provide a new technique for discriminating types of RLS, possibly aiding in the diagnosis of RLS and opening up a new area of RLS research. The approach may also be extended to other DA related conditions involving sleepiness with DA treatment. This project seeks to determine if the nocturnal CSF hypocretin of RLS patients is lower when on DA treatment and to explore the development and evaluation of anti-histamine challenge for testing RLS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UDP GLUCURONOSYLTRANSFERASES IN PHARMACOLOGY Principal Investigator & Institution: Tephly, Thomas R.; Professor; Pharmacology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-APR-1979; Project End 30-JUN-2003 Summary: Glucuronide formation is a major route of xenobiotic and endobiotic metabolism in humans. UDP-glucuron-osyltransferases (UGTs), protein products of a supergene family, mediate these reactions whereby hydrophobic compounds (aglycones) are conjugated to glucuronic acid, forming metabolites which are rapidly excreted by the kidney or liver. Four areas of research are planned. First, the significance of the polymorphic isoforms of UGT2B7 in the metabolism of certain substrates (losartan and zidovudine) will be explored using HK293 cell lines stable expressing these proteins. Using hepatic microsomes from individuals homozygous for these polymorphic isoforms, studies will address the question of whether inter-individual variation in AZT glucuronidation can be predicted base don the genotype of the individual. mRNA and glucuronidation activities for UGT2B7 and UGT1A6 have been found in human brain. Studies are proposed to use immunohistochemical localization to identify the cell types that express these proteins in the brain. Since immunohistochemical localization to identify the cell types that express these proteins in the brain. Since UGT2B7 catalyzes the formation of morphine-6-glucuronide (which is 50 times more potent that morphine as an analgesic) it is important to know where in the rain morphine-6-glucuronide can be formed because its local formation may account for part of the mechanism of action of morphine. Studies determining the substrate specificities of UGTs expressed in intestine, 1A8 and 1A5, are proposed. These isoforms are not expressed in liver and, therefore, may play an important role in xenobiotic and endobiotic metabolism in the intestine. UGT1A4 is an important enzyme because it catalyzes the glucuronidation of tertiary amines (e.g., anti-histamines) and progestins, whereas UGT1A3 catalyzes the glucuronidation of estrogens and NSAIDs. Studies are proposed that will investigate how the protein structure of UGT1A3 and UGT1A4 affects the function of the expressed enzymes. Chimeric proteins and amino acid substitutions will examine the aglycone binding sites for substrates which are unique to each protein and which are common for each UGT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Histamines

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 “histamines” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for histamines in the PubMed Central database: •

Effect of Histamine and Its Methyl Derivatives on Cyclic AMP Metabolism in Gastric Mucosa and Its Blockade by an H2 Receptor Antagonist. by Dousa TP, Code CF.; 1974 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301469

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with histamines, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “histamines” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for histamines (hyperlinks lead to article summaries): •

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1-alkyl-4-acylpiperazines as a new class of imidazole-free histamine H(3) receptor antagonists. Author(s): Zaragoza F, Stephensen H, Knudsen SM, Pridal L, Wulff BS, Rimvall K. Source: Journal of Medicinal Chemistry. 2004 May 20; 47(11): 2833-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139761

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. 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.

Studies

7

•

4-(omega-(alkyloxy)alkyl)-1H-imidazole derivatives as histamine H(3) receptor antagonists/agonists. Author(s): Meier G, Krause M, Huls A, Ligneau X, Pertz HH, Arrang JM, Ganellin CR, Schwartz JC, Schunack W, Stark H. Source: Journal of Medicinal Chemistry. 2004 May 6; 47(10): 2678-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15115409

•

8R-lisuride is a potent stereospecific histamine H1-receptor partial agonist. Author(s): Bakker RA, Weiner DM, ter Laak T, Beuming T, Zuiderveld OP, Edelbroek M, Hacksell U, Timmerman H, Brann MR, Leurs R. Source: Molecular Pharmacology. 2004 March; 65(3): 538-49. Erratum In: Mol Pharmacol. 2004 April; 65(4): 1048. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14978232

•

A double-blind controlled clinical trial to assess the role of anti-histamines in the treatment of multi-bacillary leprosy. Author(s): Thomas A, Nagarajan M, Chandrasekaran V, Hari L, Somasundaram PR, Prabhakar R, Kumar A, Bhatia VN, Roy RG. Source: Indian J Lepr. 1988 October; 60(4): 499-505. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3075630

•

A new class of diamine-based human histamine H3 receptor antagonists: 4(aminoalkoxy)benzylamines. Author(s): Apodaca R, Dvorak CA, Xiao W, Barbier AJ, Boggs JD, Wilson SJ, Lovenberg TW, Carruthers NI. Source: Journal of Medicinal Chemistry. 2003 August 28; 46(18): 3938-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930154

•

A new histamine measurement system employing a confocal laser microscope and cultured human dermal microvascular endothelial cells. Author(s): Yahata Y, Murakami S, Hashimoto K. Source: Journal of Dermatological Science. 2003 September; 32(3): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507445

•

A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. Author(s): Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, Nguyen S, Riley JP, Sun S, Williams KN, Edwards JP, Karlsson L. Source: The Journal of Pharmacology and Experimental Therapeutics. 2004 April; 309(1): 404-13. Epub 2004 January 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722321

8

Histamines

•

A study comparing the inhibitory effects of single and repeated oral doses of ebastine and fexofenadine against histamine-induced skin reactivity. Author(s): Barbanoj MJ, Antonijoan RM, Garcia-Gea C, Morte A, Gich I, Gispert J, Garcia E, Esbri R, Luria X. Source: International Archives of Allergy and Immunology. 2003 November; 132(3): 2637. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646388

•

Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction. Author(s): Kawano T, Matsuse H, Kondo Y, Machida I, Saeki S, Tomari S, Mitsuta K, Obase Y, Fukushima C, Shimoda T, Kohno S. Source: International Archives of Allergy and Immunology. 2004 July; 134(3): 233-9. Epub 2004 June 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15178893

•

Acetylcholine, histamine, and cognition: two sides of the same coin. Author(s): Blandina P, Efoudebe M, Cenni G, Mannaioni P, Passani MB. Source: Learning & Memory (Cold Spring Harbor, N.Y.). 2004 January-February; 11(1): 1-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747511

•

Activation of the canonical beta-catenin pathway by histamine. Author(s): Diks SH, Hardwick JC, Diab RM, van Santen MM, Versteeg HH, van Deventer SJ, Richel DJ, Peppelenbosch MP. Source: The Journal of Biological Chemistry. 2003 December 26; 278(52): 52491-6. Epub 2003 October 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563838

•

Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Author(s): Mothes N, Heinzkill M, Drachenberg KJ, Sperr WR, Krauth MT, Majlesi Y, Semper H, Valent P, Niederberger V, Kraft D, Valenta R. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 September; 33(9): 1198-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956739

•

Analysis of histamine and modeling of ligand-receptor interactions in the histamine H(1) receptor for Magic Angle Spinning NMR studies. Author(s): Prasad Ratnala VR, Hulsbbergen FB, de Groot HJ, de Grip WJ. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2003 October; 52(10): 417-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520517

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9

•

Antihistamines added to an antileukotriene in treating seasonal allergic rhinitis: histamine and leukotriene antagonism. Author(s): Ciprandi G, Tosca MA, Milanese M, Schenone G, Ricca V. Source: Allerg Immunol (Paris). 2004 February; 36(2): 67-70, 72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061398

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Anti-obesity actions of mastication driven by histamine neurons in rats. Author(s): Sakata T, Yoshimatsu H, Masaki T, Tsuda K. Source: Experimental Biology and Medicine (Maywood, N.J.). 2003 November; 228(10): 1106-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610247

•

Appraisal of the validity of histamine-induced wheal and flare to predict the clinical efficacy of antihistamines. Author(s): Monroe EW, Daly AF, Shalhoub RF. Source: The Journal of Allergy and Clinical Immunology. 1997 February; 99(2): S798-806. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9042073

•

Beyond the histamine receptor: effect of antihistamines on mast cells. Author(s): Cuss FM. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 July; 29 Suppl 3: 54-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10444213

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Cardiotoxicity of histamine and the possible role of histamine in the arrhythmogenesis produced by certain antihistamines. Author(s): Llenas J, Cardelus I, Heredia A, de Mora F, Gristwood RW. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1999; 21 Suppl 1: 33-8; Discussion 81-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10597866

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Comparative activity of cetirizine and desloratadine on histamine-induced whealand-flare responses during 24 hours. Author(s): Purohit A, Melac M, Pauli G, Frossard N. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2004 June; 92(6): 635-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15237765

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Compared pharmacological characteristics in humans of racemic cetirizine and levocetirizine, two histamine H1-receptor antagonists. Author(s): Tillement JP, Testa B, Bree F. Source: Biochemical Pharmacology. 2003 October 1; 66(7): 1123-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505791

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Comparison of the effects of desloratadine and levocetirizine on histamine-induced wheal, flare and itch in human skin. Author(s): Denham KJ, Boutsiouki P, Clough GF, Church MK. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2003 October; 52(10): 424-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520518

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D-amino acid homopiperazine amides: discovery of A-320436, a potent and selective non-imidazole histamine H(3)-receptor antagonist. Author(s): Curtis MP, Dwight W, Pratt J, Cowart M, Esbenshade TA, Krueger KM, Fox GB, Pan JB, Pagano TG, Hancock AA, Faghih R, Bennani YL. Source: Archiv Der Pharmazie. 2004 April; 337(4): 219-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15146898

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Distinct effects of sphingosine-1-phosphate, lysophosphatidic acid and histamine in human and mouse dendritic cells. Author(s): Renkl A, Berod L, Mockenhaupt M, Idzko M, Panther E, Termeer C, Elsner P, Huber M, Norgauer J. Source: International Journal of Molecular Medicine. 2004 February; 13(2): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719124

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Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings. Author(s): Celik I, Duda D, Stinner B, Kimura K, Gajek H, Lorenz W. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2003 October; 52(10): 408-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520516

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Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity. Author(s): Kimata H. Source: International Journal of Hygiene and Environmental Health. 2004 February; 207(2): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031958

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Effective treatment of pruritus in atopic dermatitis using H1 antihistamines (secondgeneration antihistamines): changes in blood histamine and tryptase levels. Author(s): Imaizumi A, Kawakami T, Murakami F, Soma Y, Mizoguchi M. Source: Journal of Dermatological Science. 2003 October; 33(1): 23-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527736

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Effects of amphotericin B and caspofungin on histamine expression. Author(s): Cleary JD, Schwartz M, Rogers PD, de Mestral J, Chapman SW. Source: Pharmacotherapy. 2003 August; 23(8): 966-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921242

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Effects of rofecoxib, celecoxib, and parecoxib on anti-IgE-induced histamine release from human skin mast cells and basophils. Author(s): Gibbs BF, Boehncke WH. Source: Allergy. 2003 October; 58(10): 1075-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510734

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Effects of two antihistamines on chloroquine and histamine induced weal and flare in healthy African volunteers. Author(s): Abila B, Ezeamuzie IC, Igbigbi PS, Ambakederemo AW, Asomugha L. Source: Afr J Med Med Sci. 1994 June; 23(2): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7625301

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Evaluation of the efficacy of antihistamines using human monocyte-derived dendritic cells stimulated with histamine. Author(s): Ohtani T, Aiba S, Mizuashi M, Kawamoto Y, Tagami H. Source: Journal of the American Academy of Dermatology. 2003 August; 49(2): 234-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894071

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Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells. Author(s): Fukushima Y, Ishikawa T, Saitoh T, Tateishi K, Ogihara T, Fujishiro M, Shojima N, Honda M, Kushiyama A, Anai M, Sakoda H, Ono H, Onishi Y, Otsuka H, Katagiri H, Nagai R, Omata M, Asano T. Source: Digestion. 2003; 68(2-3): 145-52. Epub 2003 December 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671421

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Fish, so foul! Foodborne illness caused by combined fish histamine and wax ester poisoning. Author(s): Leask A, Yankos P, Ferson MJ. Source: Commun Dis Intell. 2004; 28(1): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072160

12

Histamines

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Generation and characterization of highly constitutive active histamine H3 receptors. Author(s): Takahashi K, Tokita S, Kotani H. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 October; 307(1): 213-8. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954820

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Genetic and pharmacological aspects of histamine H3 receptor heterogeneity. Author(s): Hancock AA, Esbenshade TA, Krueger KM, Yao BB. Source: Life Sciences. 2003 October 31; 73(24): 3043-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550847

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H(1)-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Author(s): Goudie AJ, Halford JC, Dovey TM, Cooper GD, Neill JC. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 December; 28(12): 2209; Author Reply 2210-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942144

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H1 and H2 histamine receptors are absent on Langerhans cells and present on dermal dendritic cells. Author(s): Ohtani T, Aiba S, Mizuashi M, Mollah ZU, Nakagawa S, Tagami H. Source: The Journal of Investigative Dermatology. 2003 November; 121(5): 1073-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708609

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Histamine and antihistamines in anaphylaxis. Author(s): Winbery SL, Lieberman PL. Source: Clin Allergy Immunol. 2002; 17: 287-317. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12113221

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Histamine and epidermal growth factor in women with fibrocystic changes of the breast. Author(s): Sieja K, Stanosz S, Glowinska N. Source: Breast (Edinburgh, Scotland). 2003 April; 12(2): 99-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659338

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Histamine chloramine reactivity with thiol compounds, ascorbate, and methionine and with intracellular glutathione. Author(s): Peskin AV, Winterbourn CC. Source: Free Radical Biology & Medicine. 2003 November 15; 35(10): 1252-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607524

Studies

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Histamine dihydrochloride and cancer. Author(s): Hamill FA. Source: Integrative Cancer Therapies. 2003 March; 2(1): 91-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941175

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Histamine downregulates CD14 expression via H2 receptors on human monocytes. Author(s): Takahashi HK, Morichika T, Iwagaki H, Tamura R, Kubo S, Yoshino T, Mori S, Akagi T, Tanaka N, Nishibori M. Source: Clinical Immunology (Orlando, Fla.). 2003 September; 108(3): 274-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499251

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Histamine enhances the production of granulocyte-macrophage colony-stimulating factor via protein kinase Calpha and extracellular signal-regulated kinase in human keratinocytes. Author(s): Kanda N, Watanabe S. Source: The Journal of Investigative Dermatology. 2004 April; 122(4): 863-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15102074

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Histamine enhances the production of nerve growth factor in human keratinocytes. Author(s): Kanda N, Watanabe S. Source: The Journal of Investigative Dermatology. 2003 September; 121(3): 570-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925217

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Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans. Author(s): Matsuda N, Jesmin S, Takahashi Y, Hatta E, Kobayashi M, Matsuyama K, Kawakami N, Sakuma I, Gando S, Fukui H, Hattori Y, Levi R. Source: The Journal of Pharmacology and Experimental Therapeutics. 2004 May; 309(2): 786-95. Epub 2004 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752062

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Histamine H2-receptor antagonists have no clinically significant effect on the steadystate pharmacokinetics of voriconazole. Author(s): Purkins L, Wood N, Kleinermans D, Nichols D. Source: British Journal of Clinical Pharmacology. 2003 December; 56 Suppl 1: 51-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616414

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Histamine H3 receptor: a potential drug target for the treatment of central nervous system disorders. Author(s): Alguacil LF, Perez-Garcia C. Source: Curr Drug Targets Cns Neurol Disord. 2003 October; 2(5): 303-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529362

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Histamine induced airway response in pre-school children assessed by a noninvasive EMG technique. Author(s): Maarsingh EJ, van Eykern LA, Sprikkelman AB, van Aalderen WM. Source: Respiratory Medicine. 2004 April; 98(4): 363-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072177

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Histamine inhalation challenge in recurrent uvula angioedema. Author(s): Bucca CB, Brussino L, Cavalot A, Cicolin A, Cortesina G, Baron P, Pagano M, Rolla G. Source: The Journal of Allergy and Clinical Immunology. 2003 October; 112(4): 799-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564367

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Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met. Author(s): Betten A, Dahlgren C, Hermodsson S, Hellstrand K. Source: Scandinavian Journal of Immunology. 2003 September; 58(3): 321-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950678

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Histamine release in mesenteric traction syndrome during abdominal aortic aneurysm surgery: prophylaxis with H1 and H2 antihistamines. Author(s): Duda D, Lorenz W, Celik I. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 October; 51(10): 495-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477078

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Histamine skin test reactivity following single and multiple doses of azelastine nasal spray in patients with seasonal allergic rhinitis. Author(s): Pearlman DS, Grossman J, Meltzer EO. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 September; 91(3): 258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533657

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Histamine stimulates the proliferation of human articular chondrocytes in vitro and is expressed by chondrocytes in osteoarthritic cartilage. Author(s): Tetlow LC, Woolley DE. Source: Annals of the Rheumatic Diseases. 2003 October; 62(10): 991-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972479

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Histamine: A mediator of inflammation. Author(s): MacGlashan D Jr. Source: The Journal of Allergy and Clinical Immunology. 2003 October; 112(4 Suppl): S53-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530789

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Histamine-releasing factors, a heterogeneous group of different activities. Author(s): Budde IK, Aalberse RC. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 September; 33(9): 1175-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956736

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Histamines, basophils and eosinophils in severe asthma. Author(s): Charles TJ, Williams SJ, Seaton A, Bruce C, Taylor WH. Source: Clinical Science (London, England : 1979). 1979 July; 57(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=477247

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History in our lifetime: the changing nature of refractory duodenal ulcer in the era of histamine H2 receptor antagonists. Author(s): Bardhan KD, Nayyar AK, Royston C. Source: Dig Liver Dis. 2003 August; 35(8): 529-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567455

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Homogeneous time resolved fluorescence assay to measure histamine release. Author(s): Claret EJ, Ouled-Diaf J, Seguin P. Source: Combinatorial Chemistry & High Throughput Screening. 2003 December; 6(8): 789-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683484

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Identification of 4-(1H-imidazol-4(5)-ylmethyl)pyridine (immethridine) as a novel, potent, and highly selective histamine H(3) receptor agonist. Author(s): Kitbunnadaj R, Zuiderveld OP, Christophe B, Hulscher S, Menge WM, Gelens E, Snip E, Bakker RA, Celanire S, Gillard M, Talaga P, Timmerman H, Leurs R. Source: Journal of Medicinal Chemistry. 2004 May 6; 47(10): 2414-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15115383

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Identification of the interaction between the human recombinant histamine releasing factor/translationally controlled tumor protein and elongation factor-1 delta (also known as eElongation factor-1B beta). Author(s): Langdon JM, Vonakis BM, MacDonald SM. Source: Biochimica Et Biophysica Acta. 2004 April 5; 1688(3): 232-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15062873

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IFN-alpha inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release. Author(s): Chen YH, Bieneman AP, Creticos PS, Chichester KL, Schroeder JT. Source: The Journal of Allergy and Clinical Immunology. 2003 November; 112(5): 94450. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610485

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IL-4 primes human endothelial cells for secondary responses to histamine. Author(s): Wierzbicki T, Iqbal SM, Cuvelier SL, Awong G, Tibbles LA, Patel KD. Source: Journal of Leukocyte Biology. 2003 September; 74(3): 420-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949246

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Immediate skin reactivity to histamine and to allergens in cohorts of 9-year-old schoolchildren studied 16 years apart. Author(s): Ronchetti R, Villa MP, Pagani J, Martella S, Guglielmi F, Paggi B, Bohmerova Z, Falasca C, Barreto M. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 September; 33(9): 1232-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956744

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Immunohistochemical localization of histamine receptor subtypes in human inferior turbinates. Author(s): Nakaya M, Takeuchi N, Kondo K. Source: The Annals of Otology, Rhinology, and Laryngology. 2004 July; 113(7): 552-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15274415

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In vitro effects of ultraviolet A on histamine release from human basophils. Author(s): Monfrecola G, de Paulis A, Prizio E, Russo I, Carfora M, Santoianni P, Marone G. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 November; 17(6): 646-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14761130

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Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma. Author(s): Lozeva V, Tuomisto L, Tarhanen J, Butterworth RF. Source: Journal of Hepatology. 2003 October; 39(4): 522-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12971961

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Induction of tryptase and histamine release from human colon mast cells by IgE dependent or independent mechanisms. Author(s): He SH, Xie H, He YS. Source: World Journal of Gastroenterology : Wjg. 2004 February 1; 10(3): 319-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760749

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Influence of histamine and H1-receptor antagonists on ejaculated human spermatozoa: role of intrasperm Ca2+. Author(s): Gupta A, Khosla R, Gupta S, Tiwary AK. Source: Indian J Exp Biol. 2004 May; 42(5): 481-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15233472

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Inhibition and activation of histamine methyltransferase by methylated histamines. Author(s): Barth H, Lorenz W, Niemeyer I. Source: Hoppe Seylers Z Physiol Chem. 1973 September; 354(9): 1021-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4807799

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Inhibition of cytokine gene transcription by the human recombinant histaminereleasing factor in human T lymphocytes. Author(s): Vonakis BM, Sora R, Langdon JM, Casolaro V, MacDonald SM. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 October 1; 171(7): 3742-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500674

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Inhibition of histamine release from human mast cells by natural chymase inhibitors. Author(s): He SH, Xie H, Zhang XJ, Wang XJ. Source: Acta Pharmacologica Sinica. 2004 June; 25(6): 822-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15169639

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Inhibitors of tryptase as mast cell-stabilizing agents in the human airways: effects of tryptase and other agonists of proteinase-activated receptor 2 on histamine release. Author(s): He S, Aslam A, Gaca MD, He Y, Buckley MG, Hollenberg MD, Walls AF. Source: The Journal of Pharmacology and Experimental Therapeutics. 2004 April; 309(1): 119-26. Epub 2004 January 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722328

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Intravenously administered histamine increases choroidal but not retinal blood flow. Author(s): Zawinka C, Resch H, Schmetterer L, Dorner GT, Garhofer G. Source: Investigative Ophthalmology & Visual Science. 2004 July; 45(7): 2337-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15223814

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Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine-induced itch and flare response in human skin in vivo. Author(s): Willis EF, Clough GF, Church MK. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 March; 34(3): 450-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15005740

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Is an intravenous histamine H2 receptor antagonist superior to an intravenous proton pump inhibitor in acid suppression? Author(s): Kinoshita Y, Ishihara S. Source: Journal of Gastroenterology. 2004 January; 39(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767746

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Is there a role for amines other than histamines in the aetiology of scombrotoxicosis? Author(s): Clifford MN, Walker R, Ijomah P, Wright J, Murray CK, Hardy R. Source: Food Additives and Contaminants. 1991 September-October; 8(5): 641-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1818838

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Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate. Author(s): Bowdle TA, Even A, Shen DD, Swardstrom M. Source: Anesthesia and Analgesia. 2004 June; 98(6): 1692-7, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15155330

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Microfabricated on-chip-type electrochemical flow immunoassay system for the detection of histamine released in whole blood samples. Author(s): Lim TK, Ohta H, Matsunaga T. Source: Analytical Chemistry. 2003 July 15; 75(14): 3316-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570179

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Modulation of histamine release from human colon mast cells by protease inhibitors. Author(s): He SH, Xie H. Source: World Journal of Gastroenterology : Wjg. 2004 February 1; 10(3): 337-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760753

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Modulation of tryptase secretion from human colon mast cells by histamine. Author(s): He SH, Xie H. Source: World Journal of Gastroenterology : Wjg. 2004 February 1; 10(3): 323-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760750

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Neuronal sensitization for histamine-induced itch in lesional skin of patients with atopic dermatitis. Author(s): Ikoma A, Rukwied R, Stander S, Steinhoff M, Miyachi Y, Schmelz M. Source: Archives of Dermatology. 2003 November; 139(11): 1455-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623705

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Nitric oxide mediates histamine induced down-regulation of H2 receptor mRNA and internalization of the receptor protein (R1). Author(s): Schaefer U, Schneider A, Rudroff C, Neugebauer E. Source: Cellular and Molecular Life Sciences : Cmls. 2003 September; 60(9): 1968-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523557

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Omeprazole is more effective than a histamine H2-receptor blocker for maintaining a persistent elevation of gastric pH after colon resection for cancer. Author(s): Hsu TC, Su CF, Leu SC, Huang PC, Wang TE, Chu CH. Source: American Journal of Surgery. 2004 January; 187(1): 20-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706580

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Pro-apoptotic effect of high concentrations of histamine on human neutrophils. Author(s): Hur J, Kang MK, Park JY, Lee SY, Bae YS, Lee SH, Park YM, Kwak JY. Source: International Immunopharmacology. 2003 October; 3(10-11): 1491-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946446

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Quantitative determination of histamine in tears during conjunctivitis by a novel HPLC method. Author(s): Venza I, Visalli M, Ceci G, Teti D. Source: Ophthalmic Research. 2004 January-February; 36(1): 62-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15007242

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Regulation of Na/H exchanger-1 in gastroesophageal reflux disease: possible interaction of histamine receptor. Author(s): Siddique I, Khan I. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1832-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561010

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Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneous testing: Ara h2 is the most important peanut allergen. Author(s): Koppelman SJ, Wensing M, Ertmann M, Knulst AC, Knol EF. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 April; 34(4): 583-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15080811

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Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis. Author(s): Izquierdo I, Merlos M, Garcia-Rafanell J. Source: Drugs Today (Barc). 2003 June; 39(6): 451-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944997

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Sensitive flow cytometric method to test basophil activation influenced by homeopathic histamine dilutions. Author(s): Lorenz I, Schneider EM, Stolz P, Brack A, Strube J. Source: Forschende Komplementarmedizin Und Klassische Naturheilkunde = Research in Complementary and Natural Classical Medicine. 2003 December; 10(6): 316-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707480

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Stimulation of human bronchial epithelial cells by IgE-dependent histaminereleasing factor. Author(s): Yoneda K, Rokutan K, Nakamura Y, Yanagawa H, Kondo-Teshima S, Sone S. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2004 January; 286(1): L174-81. Epub 2003 August 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948934

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Stimulation of T-cell cytokine production and NK-cell function by IL-2, IFN-alpha and histamine treatment during remission of non-Hodgkin's lymphoma. Author(s): Ahlberg R, MacNamara B, Andersson M, Zheng C, Svensson A, Holm G, Hansson M, Porwit-MacDonald A, Bjorkholm M, Sundblad A. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(5): 336-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14502258

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Synthesis and pharmacological identification of neutral histamine H1-receptor antagonists. Author(s): Govoni M, Bakker RA, van de Wetering I, Smit MJ, Menge WM, Timmerman H, Elz S, Schunack W, Leurs R. Source: Journal of Medicinal Chemistry. 2003 December 18; 46(26): 5812-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667234

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Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists. Author(s): Kitbunnadaj R, Zuiderveld OP, De Esch IJ, Vollinga RC, Bakker R, Lutz M, Spek AL, Cavoy E, Deltent MF, Menge WM, Timmerman H, Leurs R. Source: Journal of Medicinal Chemistry. 2003 December 4; 46(25): 5445-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640553

Studies

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The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs. Author(s): Lassen LH, Christiansen I, Iversen HK, Jansen-Olesen I, Olesen J. Source: Cephalalgia : an International Journal of Headache. 2003 November; 23(9): 87786. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616929

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The effects of a new generation of H1 antihistamines (cetirizine and loratadine) on histamine release and the bronchial response to histamine in atopic patients. Author(s): Chyrek-Borowska S, Siergiejko Z, Michalska I. Source: J Investig Allergol Clin Immunol. 1995 March-April; 5(2): 103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7655699

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The effects of butterbur on the histamine and allergen cutaneous response. Author(s): Jackson CM, Lee DK, Lipworth BJ. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2004 February; 92(2): 250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14989395

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The first potent and selective non-imidazole human histamine H4 receptor antagonists. Author(s): Jablonowski JA, Grice CA, Chai W, Dvorak CA, Venable JD, Kwok AK, Ly KS, Wei J, Baker SM, Desai PJ, Jiang W, Wilson SJ, Thurmond RL, Karlsson L, Edwards JP, Lovenberg TW, Carruthers NI. Source: Journal of Medicinal Chemistry. 2003 September 11; 46(19): 3957-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954048

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The histamine-cytokine network in allergic inflammation. Author(s): Marone G, Granata F, Spadaro G, Genovese A, Triggiani M. Source: The Journal of Allergy and Clinical Immunology. 2003 October; 112(4 Suppl): S83-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530793

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The isoflavone genistein inhibits proliferation and increases histamine content in human leukemic mast cells. Author(s): Alexandrakis MG, Kyriakou DS, Kempuraj D, Huang M, Boucher W, Seretakis D, Theoharides TC. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2003 September-October; 24(5): 373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619339

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Time-dependent observations of secretion marker levels in nasal secretion after histamine and methacholine provocations. Author(s): Pupek M, Mikulewicz W, Mielnik J, Batycka B, Katnik-Prastowska I. Source: Arch Immunol Ther Exp (Warsz). 2003; 51(4): 259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956435

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Use of 2,6-dinitro-4-trifluoromethylbenzenesulfonic acid as a novel derivatizing reagent for the analysis of catecholamines, histamines and related amines by gas chromatography with electron-capture detection. Author(s): Doshi PS, Edwards DJ. Source: Journal of Chromatography. 1979 September 1; 176(3): 359-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=546919

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

Finding Nutrition Studies on Histamines 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 “histamines” (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 “histamines” (or a synonym): •

H3 receptor assay in electrically-stimulated superfused slices of rat brain cortex; effects of N alpha-alkylated histamines and impromidine analogues. Source: van der Werf, J F Bijloo, G J van der Vliet, A Bast, A Timmerman, H AgentsActions. 1987 April; 20(3-4): 239-43 0065-4299

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Histidines, histamines and imidazoles as glycosidase inhibitors. Author(s): School of Chemical Sciences, University of East Anglia, Norwich, U.K. Source: Field, R A Haines, A H Chrystal, E J Luszniak, M C Biochem-J. 1991 March 15; 274 ( Pt 3)885-9 0264-6021

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Thrombin attenuates the stimulatory effect of histamine on Ca2+ entry in confluent human umbilical vein endothelial cell cultures. Author(s): Department of Biochemistry, Agricultural and Food Research Council Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, United Kingdom. Source: Neylon, C B Irvine, R F J-Biol-Chem. 1991 March 5; 266(7): 4251-6 0021-9258

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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

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

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

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Nutrition

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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

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

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

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

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

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

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

The following is a specific Web list relating to histamines; 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 Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html

•

Minerals Bromelain/Quercetin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,941,00.html Clemastine Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Healthnotes, Inc.; www.healthnotes.com

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Quercetin Source: Integrative Medicine Communications; www.drkoop.com Quercetin Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html •

Food and Diet Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. PATENTS ON HISTAMINES 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.8 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 “histamines” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on histamines, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Histamines By performing a patent search focusing on histamines, 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 8Adapted

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 histamines: •

Allele of human histamine H2 receptor and methods of detection of H2 receptor variants Inventor(s): Heath; Paul Roy (Sheffield, GB), Orange; Paul Richard (Sheffield, GB), Pearson; Ronald Carl Alan (Newcastle-upon-Tyne, GB), Wright; Simon Ralph (Sheffield, GB) Assignee(s): University of Sheffield (Sheffield, GB) Patent Number: 6,440,670 Date filed: December 28, 1999 Abstract: The invention relates to methods of and kits for detecting polymorphisms in a nucleic acid encoding a human histamine H.sub.2 receptor. Excerpt(s): This invention relates to the detection of variations in human H.sub.2 receptors, and more particularly to the development of new compounds useful in the sequencing and identification of a human histamine H.sub.2 receptor and their use in the diagnosis and treatment of certain human disorders, for example, brain disorders. The invention also relates to new compounds and a method for detecting an allelic polymorphic variation within the human population for the gene encoding the histamine H.sub.2 receptor and their use in the diagnosis and treatment of human disorders. The human H.sub.2 receptor was first identified by Black et al Nature (1972), 236, 385-390. This was followed by the demonstration of the receptor in the mammalian brain by Baudry et al (1975) Nature 253, 362-363, and Haas and Bucher (1975) Nature 255, 634-635. Gantz et al (1991) Biochem. Biophys. Res. Comm. 178, 3, 1386-1392 have recently identified the sequence of a human H2 receptor cDNA from gastric parietal cells by using the polymerase chain reaction (PCR) and degenerated oligonucleotide primers whose sequence was obtained from the canine H.sub.2 receptor previously cloned by this group, Gantz et al (1991) Proc. Nat. Acad. Sci. USA 88, 429-433. This sequence was characterised as an intronless gene encoding a typical seven transmembrane domain aminergic receptor protein. The receptor is coupled to heterotrimeric GTPases (G proteins), but differs from other monoamine receptors in this G protein coupled superfamily in several respects. The human gastric H.sub.2 receptor is shorter than most other. receptors in this class (359 amino acids) and lacks the two serine residues in the fifth transmembrane region (TM5). There exists instead an aspartate and a threonine residue, so far unique in this region. These two residues may be important for binding with the nitrogen atoms of the imidazole ring of histamine as suggested by Birdsall (1991) Trends in Pharmacological Sci. Jan, 12, 9-10. Web site: http://www.delphion.com/details?pn=US06440670__

Patents 29

•

Compositions containing histamine H2 agonists and methods of use in treating allergy and inflammation Inventor(s): Gamache; Daniel A. (Arlington, TX), Miller; Steven T. (Arlington, TX), Yanni; John M. (Burleson, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 6,225,332 Date filed: October 20, 1998 Abstract: Compositions containing histamine H.sub.2 agonists and methods of use for treating allergy and inflammation of the eye are disclosed. Excerpt(s): The present invention is directed to compositions containing histamine H.sub.2 agonists and methods for their use in treating allergy and inflammation. The H.sub.2 agonists of the present invention stabilize human conjunctival mast cells. The compositions are used to prevent allergic responses while also treating existing allergic conditions present in the eye. The invention is also directed to methods of preventing and treating allergic responses with the compositions. The eye, particularly the conjunctiva, has a relatively large number of mast cells. When allergens are present, they can bind to immunoglobulins on the surface of these mast cells and trigger the release of cellular contents, known as degranulation. Upon degranulation, mast cell components, including histamine, are released into the environment outside the mast cell. Through a variety of mechanisms, these components can be responsible for symptoms associated with allergic responses such as itching, redness, lid swelling, vasodilatation and chemosis. Various therapies have been pursued in order to treat the symptoms of allergies. For example, such therapy has included the use of anti-allergics and histamine H,-receptor antagonists (anti-histamines). Web site: http://www.delphion.com/details?pn=US06225332__

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DNA encoding as human histamine receptor of the H3 subtype Inventor(s): Erlander; Mark (Encinitas, CA), Huvar; Arne (Santee, CA), Lovenberg; Timothy W. (San Diego, CA), Pyati; Jayashree (San Diego, CA) Assignee(s): Ortho Pharmaceutical Corporation (Raritan, NJ) Patent Number: 6,136,559 Date filed: October 7, 1998 Abstract: DNAs encoding the human histamine H3 receptor have been cloned and characterized. The recombinant protein is capable of forming biologically active histamine H3 receptor protein. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified. Excerpt(s): Histamine is a multifunctional chemical transmitter that signals through cell surface receptors that are linked to intracellular pathways via guanine nucleotide binding proteins. This class of cell surface receptors are called G-protein coupled receptors or GPCRs. There are currently three subtypes of histamine receptors that have been defined pharmacologically and have been divided into H1, H2, and H3 classifications (Hill, et al. 1997). The H1 histamine receptor has been cloned (Yamashita,

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et al. 1991)and is the target of drugs such as diphenhydramine to block the effects of histamine in allergic responses. The H2 histamine receptor has been cloned (Gantz et al. 1991) and is the target of drugs such as ranitidine to block the effects of histamine on acid secretion in the stomach. The third subtype of histamine receptor was hypothesized to exist in 1983 (Arrang, et al. 1983). It is believed to function as a presynaptic autoreceptor in histamine containing neurons in the central nervous system and as a presynaptic heteroreceptor in non-histamine containing neurons. One of the functions of the H3 receptor is to regulate neurotransmitter release at the presynaptic site. Histamine H3 receptors are thus expressed in the central nervous system, but have also been pharmacologically identified in heart, lung, and stomach, and have been hypothesized to exist in other tissues. A DNA molecule encoding a human histamine H3 receptor has been cloned and characterized and it represents a novel member of the class of receptors that couple to G-proteins. Using a recombinant expression system functional DNA molecules encoding the human histamine H3 receptor have been isolated. The biological and structural properties of these proteins are disclosed, as is the amino acid and nucleotide sequence. The recombinant protein is useful for a variety of purposes, including but not limited to identifying modulators of the human histamine H3 receptor. Modulators identified in the assays disclosed herein are useful, for example, as therapeutic agents, and diagnostic agents. Indications for said therapeutic agents include, but are not limited to, central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behavior, panic attacks, pain, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycemia, constipation, arrhythmia, disorders of the neuroendrocrine system, stress, and spasticity, as well as acid secretin, ulcers, airway constriction, asthma, allergy, inflammation, and prostate dysfunction. The recombinant DNA molecules, and portions thereof, are useful for isolating homologues of the DNA molecules, identifying and isolating genomic equivalents of the DNA molecules, and identifying, detecting or isolating mutant forms of the DNA molecules. The present invention relates to DNA encoding human histamine H3 receptor which was isolated from a cDNA library from human thalamus. The human histamine H3 receptor, as used herein, refers to protein which can specifically function as a receptor for histamine of the H3 subclass. Web site: http://www.delphion.com/details?pn=US06136559__ •

Ectoparasite histamine releasing factor, genes and uses thereof Inventor(s): Stiegler; Gary L. (Ft. Collins, CO) Assignee(s): Heska Corporation (Ft. Collins, CO) Patent Number: 6,063,902 Date filed: January 7, 1998 Abstract: The present invention relates to ectoparasite histamine releasing factor (HRF) proteins; to ectoparasite HRF nucleic acid molecules, including those that encode such HRF proteins; to antibodies raised against such HRF proteins; and to compounds that inhibit ectoparasite HRF activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such

Patents 31

proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to reduce ectoparasite burden of animals. Excerpt(s): The present invention relates to novel ectoparasite histamine releasing factor (HRF) nucleic acid molecules, to proteins encoded by such nucleic acid molecules, to antibodies raised against such proteins, and to inhibitors of such proteins, as well as to the use of such compositions to reduce ectoparasite infestation. Ectoparasite infestation of animals is of health and economic concern because ectoparasites are known to cause and/or transmit a variety of diseases. Ectoparasites cause and/or carry infectious agents that cause, for example, allergy dermatitis, anemia, murine typhus, plague and tapeworm. In addition, ectoparasites, in particular fleas, are a problem for animals maintained as pets because the infestation becomes a source of annoyance for the pet owner who may find his or her home generally contaminated with ectoparasites which feed on the pets. As such, ectoparasites are a problem not only when they are on an animal but also when they are in the general environment of the animal. In addition, ectoparasite bites, such as flea bites, can cause a hypersensitive response in animals. For example, hypersensitive responses to flea bites is manifested in a disease called flea allergy dermatitis (FAD). Hypersensitivity refers to a state of altered reactivity in which an animal, having been previously exposed to a compound, exhibits an allergic response to the compound upon subsequent exposures. There are four major types of hypersensitive responses (described in detail in, for example, Janeway et al., in Immunobiology, Garland Publishers, N.Y., N.Y., 1994). FAD can have manifestations of both immediate and delayed-type hypersensitivity. Typically, an immediate hypersensitive response in an animal susceptible to FAD includes wheal formation at the site of a bite. Such wheals can develop into a papule with a crust, representative of delayed-type hypersensitivity. Web site: http://www.delphion.com/details?pn=US06063902__ •

Effervescent histamine H2 antagonist composition Inventor(s): Hussein; Mamoun M. (Mountain Lakes, NJ), Migton; John (Clark, NJ) Assignee(s): Bristol-Myers Squibb Company (New York, NY) Patent Number: 6,264,984 Date filed: December 6, 1999 Abstract: A histamine H.sub.2 antagonist incompatible with acidic materials is incorporated in an effervescent composition and is stable therein provided the acidulant employed in the effervescent couple is a non-hydroxy group containing acidulant and such acidulant is employed as substantially the entire amount of the acidulant present in the formulation. Preferably the composition is devoid of hydroxy group containing acidulant. Adipic acid, succinic acid, fumaric acid and succinic anhyride may be employed as the acidulant. Adipic acid is preferred. Excerpt(s): This invention relates to effervescent compositions containing histamine H.sub.2 antagonists incompatible with acidulants and more particularly, it relates to effervescent histamine H2 antagonists containing compositions containing certain acidulants found to be compatible with such antagonists. Effervescent compositions usually comprise excipients, active ingredients, and a source of carbon dioxide typically referred to as an effeverscent couple. Effervescent couples are usually composed of an alkaline bicarbonate or carbonate and an acid. In the presence of water, the alkaline bicarbonate or carbonate and the acid generate carbon dioxide. Thus, effeverscent

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compositions are extremely sensitive to moisture. This necessitates special steps to protect the raw materials and the finished formulation from exposure to moisture, throughout the manufacturing process and thereafter. Anhydrous citric acid is the most commonly employed acidulant in the manufacture of effeverscent compositions. Anhydrous citric acid is however, extremely hygroscopic. So also are the most commonly employed sources of carbon dioxide, i.e, alkali bicarbonates and carbonates. The aforementioned problems are compounded when an effervescent composition is to contain, as the active, a histamine H.sub.2 antagonist. Histamine H.sub.2 antagonists are incompatible with acids, particularly the acids employed in effervescent compositions. Published EP Patent specification No. 233853 discloses that use of citric acid in effervescent compositions containing a histamine H.sub.2 antagonist evidences incompatibility of the H.sub.2 antagonist with the acids contained in the effervescent composition. In an effort to resolve this, citric acid was replaced by a mixture of monoand di- alkaline citrates. Web site: http://www.delphion.com/details?pn=US06264984__ •

Elevation of circulating blood histamine levels Inventor(s): Gehlsen; Kurt R. (Carlsbad, CA), Hellstrand; Kristoffer (Goteborg, SE), Hermodsson; Svante (Molndal, SE) Assignee(s): Maxim Pharmaceuticals, Inc. (San Diego, CA) Patent Number: 6,071,942 Date filed: November 13, 1997 Abstract: Methods for obtaining beneficial stable levels of circulating histamine are disclosed for use in methods for enhancing natural killer cell cytotoxicity and for elevating histamine levels in individuals in need thereof. In such methods, a beneficial level of circulating histamine is attained and an agent whose ability to enhance natural killer cell cytotoxicity is augmented by histamine is administered. Alternatively, stable beneficial levels of circulating histamine can be attained in subjects receiving chemotherapy or antiviral treatment. The invention may also be employed in treatments combining histamine, agents which enhance natural killer cell cytotoxicity, and chemotherapeutic agents. Optimization of the delivery of histamine and substances which induce the release of endogenous histamine are also disclosed. Excerpt(s): The present invention relates to methods of treating cancer or infectious disease in which histamine is administered in conjunction with additional agents. The additional agent may be an agent which stimulates the proliferative and/or cytotoxic activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) in a synergistic fashion with histamine. Alternatively, the additional agent may be a chemotherapeutic, antiviral, vaccine or antibiotic agent. Methods combining histamine, agents which act synergistically with histamine to enhance the cytotoxicity of NK cells and CTLs, and chemotherapeutic agents are also contemplated. The invention also relates to a method of elevating circulating blood histamine levels for prolonged periods of time in individuals with decreased circulating histamine levels. Such decreased levels may be due to cancer, viruses or other infectious agents or pathological situations. The invention is based on the surprising observation that despite previous reports of histamine's short half life in the body, it is possible to attain stable beneficial levels of circulating blood histamine and to maintain these beneficial levels for hours or days after the last administration of histamine. This observation facilitates treatments in which histamine administration to obtain beneficial levels of circulating blood histamine is combined

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with treatment with other agents. The invention also relates to improvements in the method of administering histamine. A brief review of the observations leading to the present invention is provided below to place the present invention in context. Web site: http://www.delphion.com/details?pn=US06071942__ •

H1--histamine receptor antagonists Inventor(s): Griffin; John H. (Atherton, CA), Ji; Yu-Hua (San Mateo, CA), Numerof; Robert P. (San Francisco, CA) Assignee(s): Theravance, Inc. (South San Francisco, CA) Patent Number: 6,420,560 Date filed: June 7, 1999 Excerpt(s): This invention relates to novel multibinding compounds (agents) that are H1 histamine receptor antagonists and pharmaceutical compositions comprising such compounds. Accordingly, the multibinding compounds and pharmaceutical compositions of this invention are useful in the treatment and prevention of allergic diseases such as rhinitis, urticaria, asthma, anaphylaxis, and the like. 1 HypersensitivityType I. In: Immunology. Chapter 19. Roitt, I., Brostoff, J., Male, D., Gower Medical Publishing. London, New York. (1995). 2 Histamine H1-receptor antagonists. Burger's Medicinal Chemistry and Drug Discovery. Fifth edition. Vol. 5: Wolff, M. E., Ed., John Wiley and Sons, Inc., (1997). Web site: http://www.delphion.com/details?pn=US06420560__

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Histamine H.sub.3 receptor ligands Inventor(s): Dunstone; David John (Orpington, GB), McDonald; Iain Mair (Paddock Wood, GB), Tozer; Matthew John (London, GB) Assignee(s): James Black Foundation (London, GB) Patent Number: 6,159,994 Date filed: March 13, 2000 Abstract: Compounds of formula (I) and pharmaceutically acceptable salt thereof are useful as histamine H.sub.3 receptor ligands. R.sup.1 is an optional substituent such as C.sub.1 to C.sub.6 alkyl. The moiety (1) replaces any available hydrogen atom on a carbon or nitrogen atom in the ring which includes X. R.sup.2 is C.sub.1 to C.sub.8 hydrocarbylene (in which one or more hydrogen atoms may be replaced by halogen atoms, and up to 2 carbon atoms may be replaced by oxygen, nitrogen or sulfur atoms); R.sup.3 replaces any available hydrogen atom on a carbon or nitrogen atom in the ring which includes X, and is hydrogen or C.sub.1 to C.sub.15 hydrocarbyl (in which one or more hydrogen atoms may be replaced by halogen atoms, and up to 3 carbon atoms may be replaced by oxygen, nitrogen or sulfur atoms); the (or each) R.sup.4 group is independently selected from H, non-aromatic C.sub.1 to C.sub.6 hydrocarbyl, and aryl (C.sub.1 to C.sub.3 alkyl); X is --SO-- or --SO.sub.2 --; Y and Z are each hydrogen, or together represent.dbd.O or --N--R.sup.5, wherein R.sup.5 is H, non-aromatic C.sub.1 to C.sub.6 hydrocarbyl, or aryl (C.sub.1 to C.sub.3 alkyl), or one of Y and Z is non-aromatic C.sub.1 to C.sub.6 hydrocarbyl, or aryl (C.sub.1 to C.sub.3 alkyl) and the other is H; a is from 0 to 2; and n is 1 or 2.

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Excerpt(s): This invention relates to compounds which bind to histamine H.sub.3 receptors, and to methods of making such compounds. Histamine is well known as a mediator in certain hypersensitive reactions of the body, such as allergic rashes, hayfever and asthma. These conditions are now commonly treated with potent antagonists of histamine, so-called "antihistamines". In the 1940s, it was noted that some physiological effects of histamine, such as increased gastric acid secretion and cardiac stimulation, were not blocked by the antihistamines which were then available. This led to the proposal that histamine receptors exist in at least two distinct types, referred to as H.sub.1 and, H.sub.2 receptors. Subsequently, H.sub.2 antagonists (such as cimetidine, ranitidine and famotidine) were identified, and they have become important in the treatment of gastric ulcers. Web site: http://www.delphion.com/details?pn=US06159994__ •

Histamine-N-methyltransferase variants associated with histaminergic disease Inventor(s): Galinsky; Raymond E. (Zionsville, IN), Lachman; Herb M. (New York, NY), Liggett; Stephen (Cincinnati, OH), Weinshilboum; Richard M. (Rochester, MN), Yan; Lan (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,316,188 Date filed: September 29, 1998 Abstract: Methods for characterizing patients diagnosed with histaminergic diseases are described. Nucleic acid molecules that include a histamine-N-methyltransferase intron variant sequence associated with a histaminergic disease also are described. Excerpt(s): This invention relates to the association of histamine-N-methyltransferase gene variants with histaminergic diseases. Histamine plays a role in allergic responses, is involved in the regulation of gastric acid secretion and also is a neurotransmitter. Histamine is inactivated by oxidative deamination in a diamine oxidase catalyzed reaction or by N-methylation in a histamine N-methyltransferase (HNMT) catalyzed reaction. The product of the N-methylation, N-methylhistamine, is converted by monoamine oxidase to N-methyl imidazole acetic acid. HNMT is an S-adenosyl-Lmethionine dependent cytosolic enzyme that contains 292 amino acids and has a relative molecular weight of 33 kDa. N-methylation is the major process responsible for termination of the neurotransmitter actions of histamine in the brain as well as a major pathway for histamine metabolism in bronchial epithelium. HNMT also is expressed highly in the human kidney where a 6-fold interindividual variation in activity is observed. HNMT activity in human red blood cells varies as a result of a common genetic polymorphism. Scott, M. C. et al., Clin. Pharmacol. Ther., 43:256-262 (1988); and Price, R. A. et al., Genet. Epidemiol., 10:123-131 (1993). Approximately 70%-90% of the variance in activity is due to inheritance. Web site: http://www.delphion.com/details?pn=US06316188__

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Human histamine H3 gene variant-2 Inventor(s): Tsui; Ping (Berwyn, PA) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA), SmithKline Beecham, p.l.c. (GB) Patent Number: 6,355,452 Date filed: March 13, 2000 Abstract: Human histamine H3 gene variant-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing Human histamine H3 gene variant-2 polypeptides and polynucleotides in diagnostic assays. Excerpt(s): This invention relates to newly identified polypeptides and polynucleotides encoding such polypeptides, to their use in diagnosis and in identifying compounds that may be agonists, antagonists that are potentially useful in therapy, and to production of such polypeptides and polynucleotides. The drug discovery process is currently undergoing a fundamental revolution as it embraces "functional genomics," that is, high throughput genome- or gene-based biology. This approach as a means to identify genes and gene products as therapeutic targets is rapidly superseding earlier approaches based on "positional cloning." A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position. Functional genomics relies heavily on highthroughput DNA sequencing technologies and the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery. Web site: http://www.delphion.com/details?pn=US06355452__

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IgE-dependent histamine-releasing factor-binding peptides Inventor(s): Chung; Junho (Seoul, KR), Jung; Jaehoon (Seoul, KR), Kim; Miyoung (Seoul, KR), Kim; Wha Jung (Seoul, KR), Lee; Kyunglim (College of Pharmacy, Ewha Womans University, 11-1, Daehyun-dong, Seoul, 120-750, KR) Assignee(s): Lee; Kyunglim (Seoul, KR) Patent Number: 6,710,165 Date filed: June 1, 2001 Abstract: Disclosed are IgE-dependent histamine-releasing factor (HRF) receptor, HRFbinding peptides and nucleic acids encoding the same, and uses thereof in the medicinal area. Excerpt(s): The present invention relates to IgE-dependent histamine-releasing factor (hereinafter, abbreviated as "HRF") receptor, HRF-binding peptides and nucleic acids encoding the same, and uses thereof. More specifically, the present invention relates to novel receptors against HRF causing allergic diseases such as asthma, rhinitis, urticaria, anaphylaxis, allergic bronchiectasis, allergies due to foods, drugs, pollen, insects, etc., hay fever, cold urticaria or atopic dermatitis, HRF-binding peptides and nucleic acid encoding the same, and uses thereof in the medicinal area. Allergies are known as being caused by inheritable hypersensitive formation of IgE in response to allergens, or disruption of balance between IL-4 (Interleukin-4) increasing IgE secretion and

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interferon decreasing IgE secretion. Upon the exposure to allergens, an immediate reaction occurs and various cells associated with inflammation are gathered, and after several hours, late-phase reaction (hereinafter, abbreviated as "LPR") occurs by histamine and other cytokines secreted from basophils, eosinophils and lymphocytes. In LPR, histamine is secreted from basophils, but allergens, which have initiated the reaction, do not exist any longer. Further, LPR is developed in only about half of patients suffered from allergies. Therefore, what causes histamine secretion from basophils and what causes development into LPR have been issues of great interest. To the present time, cytokines such as MCP-3, MCP-1 or RANTES were known as secreting histamine. But, it was found that in IgE-dependent LPR, only HRF can induce histamine secretion from basophils (MacDonald, et al., 1995), the mechanism of which has never been known. On the other hand, (Na,K)ATPase, which involves in the formation of resting membrane potential and in the balanced regulation of osmosis within cells, is also present in nerve cells, particularly nerve end or synaptosomal membranes, at a high concentration and plays an important role in neuroactivity. It was reported that in case of inhibition or loss of (Na,K)ATPase activity in nerve cell membrane, various neuropathological changes or apoptosis occurs (Lees, 1991). This is also related to the report that the intracellular ATP essential for (Na,K)ATPase activity is rapidly exhausted in cerebral ischemia or anoxia state (Martin, et al., 1994; Santos, et al., 1996). Therefore, it is believed that this enzyme activity is also inhibited in such cerebral disease states. Moreover, it was confirmed that in rat brain tissue slices, synaptosomes and in vitro culture system, in case (Na,K)ATPase activity is inhibited, neurotransmitters release is increased. From other in vivo and in vitro studies, it was suggested that neurotransmitters release is increased in ischemia or anoxia-like conditions and the resulting activation of postsynaptic cell membrane receptors is an important procedure in nerve injury (Choi, 1990; Martin, et al., 1994). Web site: http://www.delphion.com/details?pn=US06710165__ •

Method for treating histamine H3 receptor-mediated disorders with 2- or 3-aryl substituted imidazo[1,2-a] pyridines Inventor(s): Breitenbucher; J. Guy (Escondido, CA), Carruthers; Nicholas I. (Poway, CA), Li; Xiaobing (Flemington, NJ), Lovenberg; Timothy W. (San Diego, CA) Assignee(s): Ortho-McNeil Pharmaceutical, Inc. (Raritan, NJ) Patent Number: 6,489,337 Date filed: March 29, 2001 Abstract: The invention features methods of using pharmaceutically-active 2- or 3-aryl substituted imidazopyridines for the treatment of histamine H.sub.3 receptor-mediated disorders. Excerpt(s): The invention relates to methods of using pharmaceutically-active fused heterobicyclic compounds to treat or prevent disorders and conditions mediated by the histamine H.sub.3 receptor. The histamine H.sub.3 receptor is located as a presynaptic autoreceptor in the central nervous system and as a presynaptic heteroreceptor on serotonergic, noradrenergic, dopaminergic, and cholinergic neurons. The histamine H.sub.3 receptor is also located peripherally in tissues such as vascular smooth muscle cells. Proposed uses of histamine H.sub.3 antagonists include the treatment or prevention of dementia, Alzheimer's disease (Panula et al. Abstr. Society Neuroscience, 1995, 21:1977), epilepsy (Yokoyama et al. Eur. J. Pharmacol., 1993, 234:129), sleep/wake disorders (Lin et al, Br. Res., 1990, 523, 325; Monti et al., Eur. J. Pharmacol., 1991, 205,

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283) including narcolepsy, insomnia, and jet lag, eating disorders (Machidori et al. Brain Research, 1992, 590:180), motion sickness, vertigo, attention deficit hyperactivity disorder, learning and memory disorders (Barnes et al. Abstr. Society Neuroscience, 1993,19:1813), schizophrenia (Schlicker et al. Naunyn Schmiedeberg's Arch. Pharmacol., 1996, 353:325), and sequelae associated with post-ischemic reperfusion and hypertension (Imamura et al., J. Pharmacol. Expt. Ther., 1994, 271, 1259). H.sub.3 antagonists are also useful to treat or prevent neurogenic inflammation such as migraine (McLeod et al., Abstr. Society Neuroscience, 1996, 22, 2010), asthma (Ichinose et al, Eur. J. Pharmacol., 989, 174, 49), obesity, allergic rhinitis, substance abuse, bipolar disorders, manic disorders, and depression. Histamine H.sub.3 antagonists alone or in combination with a histamine H.sub.1 antagonist are believed to be useful in the treatment of upper airway allergic response or allergic rhinitis (see, e.g., U.S. Pat. Nos. 5,217,986, 5,352,707, and 5,869,479). Web site: http://www.delphion.com/details?pn=US06489337__ •

Method of counteracting harmful effects of histamine Inventor(s): Sato; Minoru (Miyagi-ken, JP), Sato; Naohiko (32-14 Chofugaoka 2-chome, Chofu-shi, Tokyo, JP), Takeuchi; Masaaki (Miyagi-ken, JP) Assignee(s): Sato; Naohiko (Tokyo, JP) Patent Number: 6,156,318 Date filed: April 4, 2000 Abstract: Harmful effects of histamine are counteracted by the administration of an antihistaminic substance comprising a water extract of a plant tissue of Stevia. Standing of the extract naturally cause fermentation to form one or more organic acids, such as lactic acid and acetic acid, thereby enhancing the antihistaminic action. The addition of at least one organic acid to the extract immediately after extraction can also enhance the antihistaminic action. Excerpt(s): The present invention relates generally to a method of counteracting harmful effects of histamine. More specifically, a method of counteracting the harmful effects of histamine by the administration of an antihistaminic substance of Stevia origin having the action of repressing various harmful effects to humans and animals is disclosed. Recently, pollen has been produced in large amounts by excessive tree planting of Japanese cedars and Japanese cypresses. Moreover, industrialization has increased air pollution or the amount of chemical substances released, so that pollenosis, which is an allergic disease due to combined pollution of the chemical substances and the pollen, has been widely spread. Against such an allergic disease, masks are worn. However, the wearing of masks is only symptomatic therapy, and it is impossible to prevent infection through eyes which cannot be covered with masks. On the other hand, stevioside and rebaudioside, primarily contained in leaves of Stevia, have a strong sweet taste in small amounts, and are used as natural sweeteners low in calories in substitution for sugar. Stevia is therefore known as a raw material for natural sweeteners low in calories. Web site: http://www.delphion.com/details?pn=US06156318__

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Methods of use of histamine H2 agonists in treating dry eye Inventor(s): Gamache; Daniel A. (Arlington, TX), Miller; Steven T. (Arlington, TX), Yanni; John M. (Burleson, TX) Assignee(s): Alcon Laboratories, Inc. (Fort Worth, TX) Patent Number: 6,274,160 Date filed: April 19, 2000 Abstract: A topical ophthalmic composition for the treatment of dry eye in humans, comprising one or more histamine H.sub.2 agonists, is disclosed. Excerpt(s): The present invention is directed to compositions containing histamine H.sub.2 agonists and methods for their use in treating dry eye. The H.sub.2 agonists of the present invention stimulate the release of mucins in the eye. The invention is also directed to methods of preventing and treating dry eye with the compositions of the present invention. Dry eye, also known generically as keratoconjunctivitis sicca, is a common ophthalmological disorder affecting millions of Americans each year. The condition is particularly widespread among post-menopausal women due to hormonal changes following the cessation of fertility. Dry eye may afflict an individual with varying severity. In mild cases, a patient may experience burning, a feeling of dryness, and persistent irritation such as is often caused by small bodies lodging between the eye lid and the eye surface. In severe cases, corneal damage may occur leading to impaired vision. Other diseases, such as Sjogren's disease and cicatricial pemphigoid manifest dry eye complications. Although it appears that dry eye may result from a number of unrelated pathogenic causes, all presentations of the complication share a common effect, that is the breakdown of the pre-ocular tear film, which results in dehydration of the exposed outer surface and many of the symptoms outlined above (Lemp, Report of the Nation Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes, The CLAO Journal, volume 21, number 4, pages 221-231 (1995)). Web site: http://www.delphion.com/details?pn=US06274160__

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N-(imidazolylalkyl)substituted cyclic amines as histamine-H.sub.3 agonists or antagonists Inventor(s): Afonso; Adriano (West Caldwell, NJ), Rosenblum; Stuart B. (West Orange, NJ), Wolin; Ronald (Bedminister, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,133,291 Date filed: October 16, 1998 Abstract: The present invention discloses novel N(imidazolylalkyl)-substituted cyclic amine compounds which have excellent histamine-H.sub.3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such cyclic amines as well as methods of using them to treat allergy, inflammatory and CNS-related diseases. Excerpt(s): The present invention relates to N-(imidazolylalkyl) substituted cyclic amine compounds having valuable pharmacological properties, especially central nervous system ("CNS") activities and activity against inflammatory disease and allergic conditions. Compounds of this invention are agonists or antagonists of the histamineH.sub.3 receptor. H.sub.3 receptor sites are known and are of current interest to those

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skilled in the art as a therapeutic target. U.S. Pat. No. 4,767,778 (Arrange et al) discloses certain imidazoles that behave as agonists of the H.sub.3 receptors in rat brain. European Patent Application No. 0 420 396 A2 (Smith Kline & French Laboratories Limited) and Howson et al., (Bioorg. & Med. Cherm. Letters, (1992), Vol. 2 No. 1, pp. 7778) describe imidazole derivatives having an amidine group as H3 agonists. Van der Groot et al. (Eur. J. Med. Chem. (1992) Vol. 27, pp. 511-517) describe isothiourea analogs of histamine as potent agonists or antagonists of the histamine-H3 receptor, and these isothiourea analogs of histamine overlap in part with those of the two references cited above. Clapham et al. ["Ability of Histamine-H.sub.3 Receptor Antagonists to Improve Cognition and to Increase Acetylcholine Release in vivo in the Rat", British Assn. for Psychopharmacology, Jul. 25-28 (1993), reported in J. Psychopharmacol. (Abstr. Book), A17] describe the ability of histamine-H.sub.3 receptor antagonists; to improve cognition and to increase release of acetylcholine in vivo in the rat. Clapham et al. ["Ability of the selective Histamine-H.sub.3 Receptor Antagonist Thioperamide to improve Short-term Memory and Reversal Learning in the Rat", Brit. J. Pharm. Suppl., 1993, 110, Abstract 65P] present results showing that thioperamide can improve shortterm memory and reversal learning in the rat and implicate the involvement of H.sub.3 receptors in the modulation of cognitive function. Yokoyama et al. ["Effect of Thioperamide, a Histamine-H.sub.3 Receptor Antagonist, on Electrically Induced Convulsions in Mice", Eur. J. Pharmacol., (1993), Vol. 234, pp. 129-133] report how thioperamide decreased the duration of each phase of convulsion and raised the electroconvulsive threshold, and go on to suggest that these and other findings support the hypothesis that the central histaminergic system is involved in the inhibition of seizures. International Patent Publication No. WO 9301812-A1 (SmithKline Beecham PLC) describes the use of S-[3-(4(5)-imidazolyl)propyl]isothiourea as a histamineH.sub.3 antagonist, especially for treating cognitive disorders, e.g. Alzheimer's disease and age-related memory impairment. Schlicker et al. ["Novel Histamine-H.sub.3 Receptor Antagonists: Affinities in an H.sub.3 Receptor Binding Assay and Potencies in Two Functional H.sub.3 Receptor Models", British J. Pharmacol., (1994), Vol. 112, 10431048] describe a number of imidazolylalkyl compounds wherein the imidazolylalkyl group is bonded to a guanidine group, an ester group an amide group, a thioamide group and a urea group, and compared these to thioperamide. Leurs et al. ["The Histamine-H.sub.3 -receptor: A Target for Developing New Drugs", Progr. Drug Res. (1992), Vol. 39, pp. 127-165] and Lipp et al. ["Pharmacochemistry of H.sub.3 -receptors" in The Histamine Receptor, eds.: Schwartz and Haas, Wiley-Liss, New York (1992), pp. 57-72] review a variety of synthetic H.sub.3 receptor antagonists, and Lipp et al. (ibid.) have proposed the necessary structural requirements for an H.sub.3 receptor antagonist. Reference is also made to U.S. Application, Ser. No. 08/689,951, filed Aug. 16, 1996 which claims the combined use of a histamine-H.sub.1 receptor antagonist and a histamine-H.sub.3 receptor antagonist for treatment of allergy-induced airway responses. Web site: http://www.delphion.com/details?pn=US06133291__

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Polynucleotide encoding a histamine receptor Inventor(s): Behan; Jiang X. (Edison, NJ), Hedrick; Joseph A. (South River, NJ), Laz; Thomas M. (Parlin, NJ), Monsma; Frederick J. (Summit, NJ), Morse; Kelley L. (Livingston, NJ), Umland; Shelby P. (Boonton Township, NJ), Wang; Suke (Edison, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,204,017 Date filed: October 7, 1999 Abstract: The present invention provides an isolated mammalian histamine receptor, isolated or recombinant nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods of making the receptor using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the receptor and are useful for treating medical conditions caused or mediated by histamine. Also provided are screening methods for identifying specific agonists and antagonists of the mammalian histamine receptor. Excerpt(s): The present invention relates to mammalian histamine receptors. More particularly, it relates to human histamine receptors, isolated nucleic acids and recombinant vectors encoding the receptors, to methods of making the receptors, to methods of making fragments or fusion proteins of the receptors using recombinant DNA methodology or chemical synthesis, and to methods of using the receptors in screening systems to identify agonists and antagonists of the receptors useful for the treatment of various diseases. Histamines are implicated in a number of medical conditions, including inflammation, asthma, allergy, atopic dermatitis, stroke, myocardial infection, migraine, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis. Histamines regulate the intensity and duration of immune responses and are involved in cell-to-cell communication. Histamines are also involved in leukocyte migration and bronchovasoconstriction. As established by radioligand binding, physiological assays, and molecular cloning, different types of receptors for histamines exist. Furthermore, specific histamine receptor subtypes are involved in specific medical conditions such that drugs with subtype selectivity can be utilized to target individual medical conditions. In view of the important role that histamines play in many physiological processes and medical conditions, there is a need for materials and methods useful for the identification of agonists and antagonists selective for the specific types of histamine receptors. Web site: http://www.delphion.com/details?pn=US06204017__

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Treatment of inflammatory bowel disease using histamine H.sub.3 -receptor agonists Inventor(s): Guglietta; Antonio (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,028,095 Date filed: October 11, 1999 Abstract: The present invention comprises a method for treating inflammatory bowel disease (IBD) by administering to a mammal in need thereof a therapeutically effective amount of at least one histamine H.sub.3 -receptor agonist. It has been unexpectedly

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found that H.sub.3 -receptor agonists are effective at alleviating the effects of IBD and, therefore, are useful for treating IBD, including ulcerative colitis and Crohn's disease. Excerpt(s): This invention relates to a method for treating inflammatory bowel disease by administering histamine H.sub.3 receptor agonists. Histamine (2-(4imidazolyl)ethylamine) is found naturally in most tissues of both plants and animals. It exerts its biologic actions by combining with cellular receptors located in or on the surface membrane. There are at least three distinct types of receptors: H.sub.1, H.sub.2, and H.sub.3. Some of the known effects of histamine are exerted on smooth muscle and cardiac muscle, on endothelial and nerve cells, and on the secretory cells of the stomach. The histamine H.sub.3 receptor is the latest receptor to have been identified (e.g., Arrang et al., Nature, 327:117 (1987) and Vander Werf et al., Trends Pharmacol. Sci., 10:159 (1989)). Stimulation of this receptor with H.sub.3 receptor agonists has been employed to treat a variety of conditions such as anxiety, allergy, gastrointestinal ulcers, cardiovascular diseases, central nervous system disorders, psychiatric disorders, sexual dysfunction, and sleep disorders. The majority of the compounds synthesized for this purpose are derivatives of histamines, in other words, 2-substituted imidazoles. Web site: http://www.delphion.com/details?pn=US06028095__ •

Use of a histamine antagonist, an interleukin-1 antagonist and/or a TNF.alpha.antagonist in a cosmetic, pharmaceutical or dermatological composition and composition obtained Inventor(s): Breton; Lionel (Versailles, FR), Cohen; Catherine (Paris, FR), De Lacharriere; Olivier (Paris, FR) Assignee(s): L'Oreal (Paris, FR) Patent Number: 6,277,387 Date filed: September 8, 1999 Abstract: The invention relates to the use of a histamine antagonist, an interleukin-1 antagonist and/or a TNF alpha antagonist in a cosmetic, pharmaceutical or dermatological composition for treating sensitive skins. It relates especially to the use of a histamine antagonist, an interleukin-1 antagonist and/or a TNF alpha antagonist for preventing and/or combating skin irritations and/or sores and/or erythema and/or dysaesthetic sensations and/or sensations of inflammation and/or pruritus and/or prickling and/or tingling and/or discomfort and/or tightness of the skin and/or mucosae. It also relates to a composition containing a histamine antagonist, an interleukin-1 antagonist and/or a TNF alpha antagonist which limits or eliminates the irritant side-effects of certain products, and in particular of certain cosmetic, dermatological or pharmaceutical active agents. Excerpt(s): The present invention relates to the use of a histamine antagonist, an interleukin-1 antagonist and/or a TNF alpha antagonist in a cosmetic, pharmaceutical or dermatological composition for topical application, intended, in particular, for the treatment of sensitive skins, as well as to a composition containing a histamine antagonist, an interleukin-1 antagonist and/or a TNF alpha antagonist for the purpose of decreasing or even abolishing the irritant effects of certain products, and in particular of certain active agents used in the cosmetics, pharmaceutical or dermatological field. It is known that some skins are more sensitive than others. The symptoms of sensitive skin were hitherto poorly characterized and the problem of these skins was, as a result, poorly defined; nobody understood precisely the process involved in sensitivity--non-

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allergic cutaneous hyperreactivity--of the skin. Some workers believed that a sensitive skin was a skin which reacted to cosmetic products, others that such a skin was one which reacted to several external factors, not necessarily associated with cosmetic products. Some tests have been tried in an effort to pinpoint sensitive skins, for example tests involving lactic acid and DMSO, which are known to be irritant substances: see, for example, the paper by K. Lammintausta et al., Dermatoses, 1988, 36, pages 45-49; and the paper by T. Agner and J. Scrup, Clinical and Experimental Dermatology, 1989, 14, pages 214-217. However, these tests did not enable sensitive skins to be characterized completely. Web site: http://www.delphion.com/details?pn=US06277387__

Patent Applications on Histamines As of December 2000, U.S. patent applications are open to public viewing.9 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 histamines: •

Chemical complex comprising a pyridine carboxy derivative and an H2 histamine receptor antagonist Inventor(s): Weidner, Morten Sloth; (Virum, DK) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20010027203 Date filed: March 21, 2001 Abstract: The present invention relates to a chemical composition comprising a pyridine carboxy derivative and an H2 histamine receptor antagonist and a pharmaceutical composition or a dietary supplement comprising a pyridine carboxy derivative and an H2 histamine receptor antagonist and to the use of such compositions for the preparation of a medicament or a dietary supplement for immunomodulation in a mammal and the suppression of hypersensitivity and/or inflammatory reaction. Excerpt(s): Hypersensitivity is defined as a state of altered reactivity in which the body reacts with an exaggerated immune response to a substance (antigen). Hypersensitivity may be caused by exogenous or endogenous antigens. Hypersensitivity reactions underlie a large number of diseases. Among these, allergic and autoimmune conditions are of great importance. A classification of hypersensitivity diseases is given in the textbook Clinical Medicine (Kumar, P. and Clark, M.: "Clinical Medicine", 3rd edition, p. 147-150, 1994, Bailliere Tindall, London). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

9

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

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•

Compositions containing both sedative and non-sedative antihistamines Inventor(s): Hirsh, Mark; (Wellesley, MA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N. E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20030130263 Date filed: December 5, 2001 Abstract: Compositions comprising both a sedative and a non-sedative antihistamine are disclosed as well as methods of inhibiting the release of histamines by administration of the compositions to a mammalian subject. Excerpt(s): The present invention relates to compositions comprising both a sedative and a non-sedative antihistamine. More particularly the invention relates to compositions containing the sedating antihistamine in immediate release form and the non-sedating antihistamine in delayed-release form or containing the non-sedating antihistamine in immediate release form and the sedating antihistamine in delayedrelease form. The invention further relates to methods of inhibiting the release of histamines by administration of the compositions to a mammalian subject. Hypersensitivity is an immune response after exposure to an antigen. Hypersensitivity usually causes tissue damage. Typical hypersensitivity reactions are allergic rhinitis, allergic conjunctivitis, urticaria, pruritus, sinusitis, angioedema, and anaphylaxis. Antihistamines, normally classified as H.sub.1 receptor antagonists, are used for the prophylaxis and relief of symptoms of hypersensitivity reactions. The term "antihistamine" is generally applied to Histamine H.sub.1 receptor antagonists. There are two types of antihistamines: the older antihistamines (first generation antihistamines), are associated with troublesome sedative and anti-muscarinic effects and are often called sedating antihistamines. These older antihistamines are distinguished from the newer (second generation) antihistamines which are designated as non-sedating antihistamines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Cosmetic, pharmaceutical or dermatological composition comprising a histamine antagonist, an interleukin-1 antagonist and/or a TNF-alpha antagonist Inventor(s): Breton, Lionel; (Versailles, FR), Cohen, Catherine; (Paris, FR), Lacharriere, Olivier De; (Paris, FR) Correspondence: Norman H. Stepno; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20010022978 Date filed: April 25, 2001 Abstract: The invention relates to the use of a histamine antagonist, an interleukin-1 antagonist and/or a TNF-alpha antagonist in a cosmetic, pharmaceutical or dermatological composition for treating sensitive skins. It relates especially to the use of a histamine antagonist, an interleukin-1 antagonist and/or a TNF-alpha antagonist for preventing and/or combating skin irritations and/or sores and/or erythema and/or dysaesthesic sensations and/or sensations of inflammation and/or pruritus and/or prickling and/or tingling and/or discomfort and/or tightness of the skin and/or mucosae. It also relates to a composition containing a histamine antagonist, an

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interleukin-1 antagonist and/or a TNF-alpha antagonist which limits or eliminates the irritant side-effects of certain products, and in particular of certain cosmetic, dermatological or pharmaceutical active agents. Excerpt(s): This application is a divisional of copending U.S. application Ser. No. 09/391,394, filed Sep. 8, 1999, now allowed, incorporated by reference herein in its entirety and relied upon, which is a continuation of application Ser. No. 08/879,889, filed Jun. 20, 1997, now U.S. Pat. No. 5,993,833, which is a divisional of application Ser. No. 08/580,291, filed Dec. 28, 1995, now U.S. Pat. No. 5,658,581. The present invention relates to the use of a histamine antagonist, an interleukin-1 antagonist and/or a TNFalpha antagonist in a cosmetic, pharmaceutical or dermatological composition for topical application, intended, in particular, for the treatment of sensitive skins, as well as to a composition containing a histamine antagonist, an interleukin-1 antagonist and/or a TNF-alpha antagonist for the purpose of decreasing or even abolishing the irritant effects of certain products, and in particular of certain active agents used in the cosmetics, pharmaceutical or dermatological field. It is known that some skins are more sensitive than others. The symptoms of sensitive skin were hitherto poorly characterized and the problem of these skins was, as a result, poorly defined; nobody understood precisely the process involved in sensitivity--non-allergic cutaneous hyperreactivity--of the skin. Some workers believed that a sensitive skin was a skin which reacted to cosmetic products, others that such a skin was one which reacted to several external factors, not necessarily associated with cosmetic products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

DNA encoding a human histamine receptor of the H3 subtype Inventor(s): Erlander, Mark; (Encinitas, CA), Huvar, Arne; (Santee, CA), Lovenberg, Timothy W.; (San Diego, CA), Pyati, Jayashree; (San Diego, CA) Correspondence: Woodcock Washburn Llp; One Liberty Place, 46th Floor; 1650 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20040156845 Date filed: December 2, 2003 Abstract: DNAs encoding the human histamine H3 receptor have been cloned and characterized. The recombinant protein is capable of forming biologically active histamine H3 receptor protein. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified. Excerpt(s): Histamine is a multifunctional chemical transmitter that signals through cell surface receptors that are linked to intracellular pathways via guanine nucleotide binding proteins. This class of cell surface receptors are called G-protein coupled receptors or GPCRs. There are currently three subtypes of histamine receptors that have been defined pharmacologically and have been divided into H1, H2, and H3 classifications (Hill, et al. 1997). The H1 histamine receptor has been cloned (Yamashita, et al. 1991)and is the target of drugs such as diphenhydramine to block the effects of histamine in allergic responses. The H2 histamine receptor has been cloned (Gantz et al. 1991) and is the target of drugs such as ranitidine to block the effects of histamine on acid secretion in the stomach. The third subtype of histamine receptor was

Patents 45

hypothesized to exist in 1983 (Arrang, et al. 1983). It is believed to function as a presynaptic autoreceptor in histamine containing neurons in the central nervous system and as a presynaptic heteroreceptor in non-histamine containing neurons. One of the functions of the H3 receptor is to regulate neurotransmitter release at the presynaptic site. Histamine H3 receptors are thus expressed in the central nervous system, but have also been pharmacologically identified in heart, lung, and stomach, and have been hypothesized to exist in other tissues. The present invention relates to the isolation and characterization of a human cDNA encoding a histamine H3 receptor and the uses thereof. A DNA molecule encoding a human histamine H3 receptor has been cloned and characterized and it represents a novel member of the class of receptors that couple to G-proteins. Using a recombinant expression system functional DNA molecules encoding the human histamine H3 receptor have been isolated. The biological and structural properties of these proteins are disclosed, as is the amino acid and nucleotide sequence. The recombinant protein is useful for a variety of purposes, including but not limited to identifying modulators of the human histamine H3 receptor. Modulators identified in the assays disclosed herein are useful, for example, as therapeutic agents, and diagnostic agents. Indications for said therapeutic agents include, but are not limited to, central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behavior, panic attacks, pain, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycemia, constipation, arrhythmia, disorders of the neuroendrocrine system, stress, and spasticity, as well as acid secretin, ulcers, airway constriction, asthma, allergy, inflammation, and prostate dysfunction. The recombinant DNA molecules, and portions thereof, are useful for isolating homologues of the DNA molecules, identifying and isolating genomic equivalents of the DNA molecules, and identifying, detecting or isolating mutant forms of the DNA molecules. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Histamine H2 receptor and uses Inventor(s): Jay, Gilbert; (North Bethesda, MD), Kovacs, Karl F.; (Rockville, MD) Correspondence: Origene Technologies, Incorporated; 6 Taft Court; Suite 100; Rockville; MD; 20850; US Patent Application Number: 20030113839 Date filed: December 18, 2001 Abstract: The present invention relates to the histamine H2 receptor (H2R), a member of the G-protein-coupled heptahelical receptor family. This novel H2 receptor codes for a novel carboxy-terminal tail which imparts important regulatory functions to the receptor, e.g., in down-regulation, signal transduction, and in coupling the activity of the H2R to downstream effector molecules, such as G-protein-coupled receptor kinases (GRK). The present invention relates to all facets of this new form of the H2R receptor, including nucleic acids that encode it, H2R polypeptides, binding-partners thereto, as well as its use in research, diagnosis, drug discovery, validation, and targeting, therapy, and clinical medicine. Excerpt(s): SEQ ID NO 1 shows the nucleotide sequence of a human H2R and SEQ ID NO 2 shows the amino acid sequence of a human H2R. The present invention relates to

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the histamine H2 receptor (H2R), a member of the G-protein-coupled heptahelical receptor family. A genomic DNA coding for a H2R was originally identified in 1991 from a dog genomic library. Receptor homologs were subsequently isolated from a number of mammalian species. It has now been found that the H2R receptors as previously identified were incomplete, lacking a substantial portion of the C-terminus that projects into the cell cytoplasm. Despite years of intensive research on this medically important receptor, this deficiency went unnoticed. Strikingly, the human form of this novel H2 receptor codes for a 422 amino acid polypeptide, 63 more amino acids than present in the previously known form. Compare, e.g., U.S. Pat. No. 5,885,824. These additional carboxy-terminal residues encode important regulatory functions, e.g., in down-regulation, signal transduction, and in coupling the activity of the H2R to downstream effector molecules, such as G-protein-coupled receptor kinases (GRK). The present invention relates to all facets of this new form of the H2R receptor, including nucleic acids that encode it, H2R polypeptides, binding-partners thereto, as well as its use in research, diagnosis, drug discovery, validation and targeting, therapy, and clinical medicine. Histamine is a biogenic amine involved in a number of physiological processes, including, vascular dilation, smooth muscle contraction, inflammation, and gastric acid secretion. It is also a neurotransmitter in the brain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Histamine measuring apparatus and a histamine measuring method Inventor(s): Otomo, Jun; (Tokyo, JP), Takeshita, Tomoko; (Higashimatsuyama, JP) Correspondence: Mattingly, Stanger & Malur, P.C.; 104 East Hume Avenue; Alexandria; VA; 22301; US Patent Application Number: 20010004524 Date filed: February 21, 2001 Abstract: Histamine may be quantitatively measured by providing the steps of: holding in a recess formed at the bottom of a vessel an oocyte that expresses histamine receptors, inserting first and second electrodes into the oocyte, measuring the membrane potential of the oocyte by means of said first electrode to stabilize the membrane potential of said oocyte at a predetermined level by driving a current through second electrode inserted into said oocyte by means of a circuitry for clamping membrane potential of oocyte, infusing a sample into a fine reacting tube having an antigen immobilized on the inner surface thereof together with some buffer solution to promote a histamine releasing reaction, transferring the solution containing histamine released in the fine reacting tube to the vessel to make contact with said oocyte in the vessel, detecting an electric response of oocyte caused by the contact with said solution, and determining the concentration of histamine released by said histamine releasing reaction in said fine reacting tube. The whole blood or mast cell suspension may be used as a sample without pretreatment. Excerpt(s): The present invention is directed to a histamine measuring apparatus and a histamine measuring method for quantitatively measuring histamine present in bloods or mast cells suspensions. Histamine releasing test is a quantitative analysis of histamine extracellularly released by stimulating leucocytes (white blood cells) in the blood or mast cells in the mucosa and promoting releasing histamine contained therein outside the cells. The histamine release test has been reported to be a method useful in identifying some allergens in some allergic disorders and diseases (c.f., Prior Art 1: Tabe, kazuaki: histamine release test--diagnosis of allergies, SRL HOKAN, vol 21, pp. 17-22

Patents 47

(1997). The known measurements of freed histamine (histamine released in free state) includes, for example, a method using fluorescent HPLC (fluorescent high performance liquid chromatography) to purify the histamine to react it with a fluorescent reagent in order to measure the amount of fluorescence emitted from the fluorescent reagent reacted with the histamine (c.f., Prior Art 2: Japanese Patent Laid-Open No. H6-331619), a method using glass fibers to purify the freed histamine to react it with a fluorescent reagent in order to measure the amount of fluorescence emitted from the fluorescent reagent coupled with the free histamine (c.f., Prior Art 3: Japanese Patent Laid-Open No. H10-170514, Japanese Patent Laid-Open No. 10-62415), competitive immunoassays commercially available from ICN Pharmaceuticals or immunotech, and an ELISA (c.f., Prior Art 4). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Histamine receptor Inventor(s): Behan, Jiang X.; (Edison, NJ), Hedrick, Joseph A.; (South River, NJ), Laz, Thomas M.; (Parlin, NJ), Monsma, Frederick J.; (Summit, NJ), Morse, Kelley L.; (Livingston, NJ), Umland, Shelby P.; (Boonton Twp., NJ), Wang, Suke; (Edison, NJ) Correspondence: Schering-Plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20020098539 Date filed: March 19, 2001 Abstract: The present invention provides an isolated mammalian histamine receptor, isolated or recombinant nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods of making the receptor using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the receptor and are useful for treating medical conditions caused or mediated by histamine. Also provided are screening methods for identifying specific agonists and antagonists of the mammalian histamine receptor. Excerpt(s): The present invention relates to mammalian histamine receptors. More particularly, it relates to human histamine receptors, isolated nucleic acids and recombinant vectors encoding the receptors, to methods of making the receptors, to methods of making fragments or fusion proteins of the receptors using recombinant DNA methodology or chemical synthesis, and to methods of using the receptors in screening systems to identify agonists and antagonists of the receptors useful for the treatment of various diseases. Histamines are implicated in a number of medical conditions, including inflammation, asthma, allergy, atopic dermatitis, stroke, myocardial infection, migraine, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis. Histamines regulate the intensity and duration of immune responses and are involved in cell-to-cell communication. Histamines are also involved in leukocyte migration and bronchovasoconstriction. As established by radioligand binding, physiological assays, and molecular cloning, different types of receptors for histamines exist. Furthermore, specific histamine receptor subtypes are involved in specific medical conditions such that drugs with subtype selectivity can be utilized to target individual medical conditions. In view of the important role that histamines play in many physiological processes and medical conditions, there is a need for materials and methods usefull for

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the identification of agonists and antagonists selective for the specific types of histamine receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Histamine receptor antagonists Inventor(s): Jenkinson, Stephen; (Durham, NC), O'Reilly, Mark Anthony; (Sandwich, GB), Trevethick, Michael Andrew; (Sandwich, GB) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020132755 Date filed: January 17, 2002 Abstract: The present invention provides a combination of (a) a histamine H.sub.1 receptor antagonist and (b) an antagonist that is at least 10-fold selective for the histamine H.sub.4 receptor as compared to the histamine H.sub.3 receptor; and an antagonist that is at least 10-fold selective for the histamine H.sub.4 receptor as compared to the histamine H.sub.3 receptor: and compositions and uses thereof. Excerpt(s): This invention relates to a combination of a histamine H.sub.1 receptor antagonist and a selective histamine H.sub.4 receptor antagonist for the treatment of a range of diseases that may be treated by antagonism of either or both of the H.sub.1 and H.sub.4 receptors including allergic diseases and disorders such as allergic rhinitis and asthma, to the uses of, and to compositions, products and methods of treatment including, such a combination. This invention also relates to a selective histamine H.sub.4 receptor antagonist. Allergies are widespread and affect a large proportion of the world population. They may be seasonal in nature and can be caused by a variety of factors present in the environment such as pollen, mites and dust particles. Symptoms of allergic rhinitis, which may be seasonal or perennial, can include rhinorrhea, nasal congestion and irritation, often accompanied by coughing or sneezing. Irritation and soreness of the throat and eyes is also common. The level of severity of each symptom experienced may vary from representing a minor problem to a person experiencing a severe effect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Histamine-3 receptor ligands for diabetes conditions Inventor(s): Bennani, Youssef; (Shaker Heights, OH), Bush, Eugene; (Libertyville, IL), Cowart, Marlon; (Round Lake Beach, IL), Hancock, Arthur; (Libertyville, IL), Jacobson, Peer B.; (Libertyville, IL), Opgenorth, Terry; (Racine, WI) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20030134835 Date filed: January 11, 2002 Abstract: The invention relates to a method of treating a diabetic condition by administering a therapeutically effective amount of a histamine-3 receptor antagonist, including benzofuran and benzopyran derivatives of formula (I),

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aminoalkoxybiphenylcarboxamide compounds of formula aminoetherbiphenyl compounds of formula (IV) as described herein.

(III),

and

Excerpt(s): The invention relates to a new use for compounds exhibiting histamine-3 receptor activity and compositions comprising such compounds for the treatment of diabetes and diabetes-related conditions. Histamine is a well-known mediator in hypersensitive reactions (e.g. allergies, hay fever, and asthma) which are commonly treated with antagonists of histamine or "antihistamines." It has also been established that histamine receptors exist in at least two distinct types, referred to as H.sub.1 and H.sub.2 receptors. A third histamine receptor (H.sub.3 receptor) is believed to play a role in neurotransmission in the central nervous system, where the H.sub.3 receptor is thought to be disposed presynaptically on histaminergic nerve endings (Nature 302:832837 (1983)). The existence of the H.sub.3 receptor has been confirmed by the development of selective H.sub.3 receptor agonists and antagonists (Nature 327:117-123 (1987)) and has subsequently been shown to regulate the release of other neurotransmitters in both the central nervous system and peripheral organs, particularly the lungs, cardiovascular system and gastrointestinal tract. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

I g E-dependent histamine-releasing factor (HRF) receptor, HRF-binding peptides and nucleic acids encoding the same, and uses thereof Inventor(s): Chung, Junho; (Seoul, KR), Jung, Jaehoon; (Seoul, KR), Kim, Miyoung; (Seoul, KR), Kim, Wha Jung; (Seoul, KR), Lee, Kyunglim; (Seoul, KR) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20020095023 Date filed: June 1, 2001 Abstract: Disclosed are IgE-dependent histamine-releasing factor (HRF) receptor, HRFbinding peptides and nucleic acids encoding the same, and uses thereof in the medicinal area. Excerpt(s): The present invention relates to IgE-dependent histamine-releasing factor (hereinafter, abbreviated as "HRF") receptor, HRF-binding peptides and nucleic acids encoding the same, and uses thereof More specifically, the present invention relates to novel receptors against HRF causing allergic diseases such as asthma, rhinitis, urticaria, anaphylaxis, allergic bronchiectasis, allergies due to foods, drugs, pollen, insects, etc., hay fever, cold urticaria or atopic dermatitis, HRF-binding peptides and nucleic acid encoding the same, and uses thereof in the medicinal area. Allergies are known as being caused by inheritable hypersensitive formation of IgE in response to allergens, or disruption of balance between IL-4 (Interleukin-4) increasing IgE secretion and interferon decreasing IgE secretion. Upon the exposure to allergens, an immediate reaction occurs and various cells associated with inflammation are gathered, and after several hours, late-phase reaction (hereinafter, abbreviated as "LPR") occurs by histamine and other cytokines secreted from basophils, eosinophils and lymphocytes. In LPR, histamine is secreted from basophils, but allergens, which have initiated the reaction, do not exist any longer. Further, LPR is developed in only about half of patients suffered from allergies. Therefore, what causes histamine secretion from basophils and what causes development into LPR have been issues of great interest. To the present time, cytokines such as MCP-3, MCP-1 or RANTES were known as secreting

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histamine. But, it was found that in IgE-dependent LPR, only HRF can induce histamine secretion from basophils (MacDonald, et al., 1995), the mechanism of which has never been known. HRF, which is a ubiquitous cytoplasmic protein, is a known protein consisting of 172 amino acids (Bohm, et al., 1989). 45 Amino acids at its Cterminal form basic domain. Because such domain has about 46% homology with MAP1B, microtubule-associated protein, it was assumed that HRF is also microtubuleassociated protein. Gachet, et al. (1997) observed that HRF is distributed consistently with the cytoskeletal network to some extent by using confocal microscope, which suggests that HRF binds to the cytoskeleton. Meanwhile, Sanchez, et al. (1997) published that HRF, even though it does not fall within general Ca.sup.2+-binding protein family, binds to Ca.sup.2+ and further, identified that yeast cells can survive with the deletion of HRF genes in Saccharomyces cerevisiae. These suggest that HRF falls within the gene family having redundant pathway. MacDonald, et al. (1995) also found HRF, which is an intracellular protein, in the outside of cells. Further, it was known that HRF present in the outside of cells stimulates IgE-sensitized basophils to release histamine, but an accurate interaction between IgE and HRF has not been identified (Schroeder, et al., 1996). Schroeder, et al. (1997) observed that HRF can augment the anti-IgE-induced histamine release from all basophils, regardless of the IgE type, and thus suggested that HRF exerts its function by binding to cell membrane receptors, not by binding with IgE. Accordingly, the followings have been important issues, i.e. how HRF is secreted to the outside of cells and how it stimulates IgE-sensitized basophils to release histamine. Since HRF, a hydrophilic and intracellular protein, is detected in LPR allergy patients plasma at a large amount, it was assumed to be secreted to the outside of cells by apoptosis or other mechanisms and to release histamine via HRF receptors present in basophil membrane. In addition, because this HRF exists in most of tissues, it is assumed to function in tissue cells other than in inflammatory cells. But, its functions in other tissues than inflammatory cells, particularly in cerebral tissue or nerve cells, have never been reported. Recently, HRF was found during the analysis of proteins present in human brain using 2-D gel electrophoresis and proteomics (Langen, et al., 1999). Subsequently, it was also reported that HRF protein is decreased in the brain of patients died of Down's syndrome or Alzheimer's disease (Kim, et al., 2001). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and compositions for reducing cardiac dysfunctions with a selective histamine H3 receptor agonist Inventor(s): Levi, Roberto; (New York, NY), Silver, Randi B.; (New York, NY) Correspondence: Irving N. Feit, ESQ.; Hoffmann & Baron, Llp; 6900 Jericho Turnpike; Syosset; NY; 11791; US Patent Application Number: 20020151576 Date filed: February 13, 2002 Abstract: The invention provides a method for reducing cardiac dysfunctions in a human. The method comprises administration to the human of an effective amount of a selective histamine H.sub.3 Receptor agonist. In one embodiment, the method comprises limiting the accumulation of intracellular sodium (Na.sub.i) by inhibiting the Na.sup.+/H.sup.+ exchanger activity in the human having a cardiac dysfunction, or a predisposition to a cardiac dysfunction. In another embodiment the method comprises inhibiting the N-type Ca.sup.2+ channel to modulate the concentration of intracellular

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calcium. The invention also provides a pharmaceutical composition that includes a selective histamine H.sub.3 Receptor agonist with a pharmaceutical carrier. Excerpt(s): Myocardial ischemia and infarction are associated with excessive norepinephrine (NE) release from sympathetic nerve endings (See reference 1). Cardiac dysfunctions, such as arrhythmias ensue, resulting in high morbidity and mortality. (References 2, 3). In these pathological conditions, NE is released principally by a reversal of the normal NE re-uptake pathway (NE transporter) in cardiac sympathetic nerves. This is known as "carrier mediated" release of NE in contrast to the normal exocytotic release of NE. Several lines of evidence suggest that changes in intracellular sodium (Na.sub.i) influence this pathological NE release. The anoxia resulting from myocardial ischemia perturbs the metabolism of the neuron and is characterized by intracellular acidosis, depletion of ATP stores, and accumulation of free NE in the axoplasm. A consequence of this pathological state is compromised function of the Na.sup.+ pump (Na.sup.+/K.sup.+ ATPase), which leads to accumulation of Na.sub.i. In addition, the intracellular acidosis activates the Na.sup.+/H.sup.+ exchanger (NHE) whose function is dependent on intracellular pH. NHE extrudes intracellular H.sup.+ in exchange for extracellular Na.sup.+. NHE activation exacerbates the accumulation of Na.sub.i and thereby favors the release of free NE via the NE transporter ("carrier mediated" NE release). Histamine H.sub.3 receptors (H.sub.3R, reference 7) were recently discovered to be present in cardiac sympathetic nerve endings. (References 810). To date, however, there has been no direct link between stimulation of histamine H.sub.3 receptors and inhibition of Na.sup.+/H.sup.+ exchanger activity or any other mechanism capable of regulating Na.sup.+ ion transfer in sympathetic nerve endings (SNEs). These mechanisms include the action of Na.sup.+/K.sup.+ ATPase, the voltagedependent Na.sup.+ channel, the Na.sup.+/Ca.sup.++ exchanger, the Na.sup.+/K.sup.+ exchanger and any plasma membrane protein that can mediate a change in the intracellular Na.sup.+ concentration in SNEs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ophthalmic histamine compositions and uses thereof Inventor(s): Gehlsen, Kurt R.; (Encinitas, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020098224 Date filed: November 30, 2001 Abstract: An ophthalmic composition for use in reducing ocular irritation comprising histamine, at a concentration of between about 0.01 and 1.0% by weight, in a pharmaceutically acceptable carrier, adapted for ophthalmic administration. Excerpt(s): This application claims the benefit of priority from PCT/US00/15379, filed Jun. 2, 2000, which claims the benefit of priority from Provisional Application No. 60/137,564, each of which is hereby incorporated by reference in their entirety. The present invention relates to ophthalmic histamine-containing preparations for the treatment of ocular irritation. More precisely, the invention relates to an aqueous formulation of histamine or similar compounds, to be instilled in and around the eye as well as in the conjunctival sac to treat various forms of ocular irritation. There are a number of patents that address various ophthalmic formulations to ease ocular irritation. For example, U.S. Pat. Nos. 5,895,645; 5,877,154; 5,872,086; and 5,861,148; each

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recite an ophthalmic solution formulated to ease ocular irritation. However, none of these patents discuss the use of histamine-containing formulations for the reduction of ocular irritation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Regulation of human histamine h2-like g protein-coupled receptor Inventor(s): Ramakrishnan, Shyam; (Brighton, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040136981 Date filed: April 23, 2003 Abstract: Reagents which regulate human histamine H2-like G protein-coupled receptor (histamine H2-like GPCR) and reagents which bind to human histamine H2-like GPCR gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, those of the digestive, immune, respiratory, reproductive, urinary peripheral or central nervous systems. Excerpt(s): The invention relates to the area of G-protein coupled receptors. More particularly, it relates to the area of human histamine H2-like G protein-coupled receptor and its regulation. Many medically significant biological processes are mediated by signal transduction pathways that involve G-proteins (Lefkowitz, Nature 351, 353-354, 1991). The family of G-protein coupled receptors (GPCR) includes receptors for hormones, neurotransmitters, growth factors, and viruses. Specific examples of GPCRs include receptors for such diverse agents as dopamine, calcitonin, adrenergic hormones, endothelin, cAMP, adenosine, acetylcholine, histamine H2, histamine, thrombin, kinin, follicle stimulating hormone, opsins, endothelial differentiation gene-1, rhodopsins, odorants, cytomegalovirus, G-proteins themselves, effector proteins such as phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins such as protein kinase A and protein kinase C. GPCRs possess seven conserved membrane-spanning domains connecting at least eight divergent hydrophilic loops. GPCRs (also known as 7TM receptors) have been characterized as including these seven conserved hydrophobic stretches of about 20 to 30 amino acids, connecting at least eight divergent hydrophilic loops. Most GPCRs have single conserved cysteine residues in each of the first two extracellular loops, which form disulfide bonds that are believed to stabilize functional protein structure. The seven transmembrane regions are designated as TM1, TM2, TM3, TM4, TM5, TM6, and TM7. TM3 has been implicated in signal transduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Small peptides and methods for treatment of asthma and inflammation Inventor(s): Houck, John C.; (Seattle, WA), MacDonald, Mary; (Lynden, WA) Correspondence: Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030130200 Date filed: July 9, 2002

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Abstract: A pharmaceutical composition is described as an admixture of a pharmacological carrier and a peptide having the formula f-Met-Leu-X. X is selected from the group consisting of Tyr, Tyr-Phe, Phe-Phe and Phe-Tyr. Also described are methods for inhibiting the degranulation of mast cells and for treating inflammation in a patient, for example, where the inflammation is a result of a disease selected from the group consisting of asthma, rheumatoid arthritis and anaphylaxis. In addition, methods are described for inhibiting the release of cytokines in a patient, for inhibiting the release of histamines in a patient, for inhibiting the release leukotrienes in a patient, for reducing adhesion, migration and aggregation of lymphocytes, eosinophils and neutrophils to a site of inflammation in a patient, for reducing the production of IgE antibodies at site of inflammation in a patient, and for inhibiting increased vascular permeability at site of inflammation in a patient. The methods use the described pharmaceutical composition. Excerpt(s): This invention relates to small peptides having mast cell degranulation inhibition activity and to methods for treating inflammation, and particularly to Nformyl methionyl peptides useful for the treatment of inflammation. More particularly, the invention relates to methods of treating diseases or conditions involving mast cell degranulation including, for example, asthma, rheumatoid arthritis and anaphylaxis. Asthma is a complex disorder. Both hereditary and environmental factors--allergies, viral infections, irritants--are involved in the onset of asthma and in its inflammatory exacerbations. More than half of asthmatics (adults and children) have allergies; indeed; allergy to house dust mite feces is a major factor in the development of the disease and in the occurrence of exacerbations. Infection with respiratory syncytial virus during infancy is also highly associated with the development of asthma, and viral respiratory infections often trigger acute episodes. The introduction three decades ago of bronchodilating beta.sub.2-agonists--adrenergic agonists selective for the beta.sub.2 receptor--revolutionized the treatment of asthma. These agents proved to be more potent and longer acting (4-6 hours) than the nonselective adrenergic receptor agonists such as isoproterenol, which stimulate both alpha- and beta-adrenergic receptors. Beta.sub.2-agonists give rapid symptomatic relief and also protect against acute bronchoconstriction caused by stimili such as exercise or the inhalation of frigid air. Frequency of use can also serve as an indicator of asthma control. Recently, an extra long-acting beta.sub.2-agonist-salmeterol (duration up to 12 hours) was introduced in the United States. Salmeterol is so potent that it may mask inflammatory signs; therefore, it should be used with an anti-inflammatory. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Substituted imidazoles as dual histamine H1 and H3 agonists or antagonists Inventor(s): Afonso, Adriano; (West Caldwell, NJ), Aslanian, Robert G.; (Rockaway, NJ), Lupo, Andrew T. JR.; (Emerson, NJ), Piwinski, John J.; (Clinton Township, NJ), Shih, Neng-Yang; (North Caldwell, NJ) Correspondence: Schering-Plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20020082272 Date filed: September 18, 2001 Abstract: The present invention discloses novel substituted imidazole compounds which have H.sub.3 receptor antagonist activity or dual histamine-H.sub.1 and H.sub.3 receptor antagonist activity as well as methods for preparing such compounds. In

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another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, congestion, inflammatory and CNS-related diseases and others. Excerpt(s): The present invention relates to novel substituted imidazole compounds having valuable pharmacological properties, especially against inflammatory diseases and allergic conditions. Compounds of this invention are antagonists of the histamine receptors. Some are antagonists of the histamine-H.sub.3 receptors. Some are antagonists of both the H.sub.1 and H.sub.3 receptors, in other words dual H.sub.1 and H.sub.3 receptor antagonists. The invention disclosed in this application claims priority from provisional application, Ser. No. 60/234,038 filed Sep. 20, 2000, and is related to that in pending provisional applications, Ser. No. 60/234,040, Ser. No. 60/234,039, and Ser. No. 60/234,053, all filed on Sep. 20, 2000. The histamine receptors, H.sub.1, H.sub.2 and H.sub.3 are well-identified forms. The H.sub.1 receptors are those that mediate the response antagonized by conventional antihistamines. H.sub.1 receptors are present, for example, in the ileum, the skin, and the bronchial smooth muscle of humans and other mammals. A well-known antagonist of H.sub.1 receptors is loratadine, commercially available under the tradename CLARITIN.RTM. from Schering-Plough Corporation, Madison, N.J. Through H.sub.2 receptor-mediated responses, histamine stimulates gastric acid secretion in mammals and the chronotropic effect in isolated mammalian atria. H.sub.3 receptor sites are found on sympathetic nerves, where they modulate sympathetic neurotransmission and attenuate a variety of end organ responses under control of the sympathetic nervous system. Specifically, H.sub.3 receptor activation by histamine attenuates nonepinephrine outflow to resistance and capacitance vessels, causing vasodilatation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Synergistic tumorcidal response induced by histamine Inventor(s): Gehlsen, Kurt R.; (Encinitas, CA), Hellstrand, Kristoffer; (Goteborg, SE), Hermodsson, Svante; (Molndal, SE) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20020193416 Date filed: August 9, 2002 Excerpt(s): This application is a Continuation of U.S. application Ser. No. 09/226,226, filed Jan. 6, 1999, and claims priority to U.S. application Ser. No. 09/226,226, which is hereby expressly incorporated by reference in its entirety. The present invention relates to methods of treating cancer in which histamine is administered in conjunction with other cancer therapies. The cancer therapy includes surgery, radiation, immunotherapy, the administration of an agent which enhances the humoral immune response of the patient or any combination thereof. Despite tremendous advances over the past several years, current cancer therapies fail to cure many forms of cancer. The problems faced by investigators and clinicians are numerous. Some tumors are not resectable or do not respond to radiation or chemotherapy or combinations of these procedures. Furthermore, the severe morbidity often associated with these treatments has led many to look for entirely new approaches to tumor therapy that are more specifically lethal for cancer cells and less toxic for normal cells. Attempts to promote an immune response to the tumor by immunizing the cancer patient with killed cancer cells or antigens specific for cancer cells have been largely unsuccessful and the use of monoclonal antibodies

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(mAbs) as the "magic bullet" to specifically destroy cancer cells without harming normal cells remains clinically limited. Methods that enhance the effectivity of known cancer therapies are desperately needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Synthesis of histamine dihydrochloride Inventor(s): Antczak, Casimir; (Ontario, CA), McGolrick, Jeffrey David; (Ontario, CA), Roth, Michael Joseph; (Ontario, CA), Wrona, Mark; (Ontario, CA), Yeh, Wen-Lung; (Ontario, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020035268 Date filed: October 9, 2001 Abstract: The invention disclosed herein relates to the preparation of pharmaceutical grades of histamine dihydrochloride using a two step non-enzymatic synthetic method. The invention disclosed herein describes the synthesis of histamine dihydrochloride by the non-enzymatic decarboxylation of histidine and the step-wise conversion of the decarboxylated product to the dihydrochloride salt form. The invention disclosed herein considers a final product of histamine dihydrochloride containing less than each of the following: 0.8% L-histidine HCl monohydrate, 0.1% individual chromatographic impurities, and 2% total impurities, to be acceptable for pharmaceutical use. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 09/467,652, now U.S. Pat. No. ______, which claims priority to U.S. provisional patent application No. 60/113,933, both of which are hereby incorporated by reference in their entirety. Histamine is a compound possessing significant biological activity mediated by pharmacological receptors. Histamine has long been contemplated as a molecule having primarily negative biological effects. Recently, however, new uses for histamine as a powerful pharmaceutical agent have come to light. For example, histamine has been used in conjunction with interferon-alpha to activate NK cells in the presence of monocytes. See U.S. Pat. No. 5,728,378. To take full advantage of the therapeutic properties of histamine, it is necessary to obtain large quantities of the compound in a pharmaceutical grade. Histamine occurs widely in nature as a result of putrefactive processes and a derivative, histamine dihydrochloride, is sold commercially for use as a standard in assays and as a component in certain allergy diagnostic kits. The source of this histamine is often a natural one and as such contains a variety of contaminants that render it unsuitable for pharmaceutical use. There are also synthetic protocols for the synthesis of histamine dihydrochloride known in the art. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of a composition containing an effective quantity of at least one chelating agent for partially or totally reducing the symptoms associated with histamine release in the organism Inventor(s): De Lacharriere, Olivier; (Paris, FR), Jourdain, Roland; (Meudon la Foret, FR) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030039669 Date filed: April 23, 2002 Abstract: Use to partially or totally reduce the symptoms associated with histamine release in the organism, particularly pruritus and erythema, which comprises the topical application of a cosmetic and/or dermatological and/or hygiene composition containing an effective quantity of at least one ion chelating agent, said composition being essentially free of flavones, flavonones and/or flavonoids, and free of sequestring agents such as polyaspartic acid and its salts, cellulose derivatives and copolymers containing maleic or hydrosuccinic acid as monomeric building blocks and salts thereof. Excerpt(s): The present invention relates to the use of a composition containing an effective quantity of at least one chelating agent for partially or totally eliminating the symptoms associated with histamine release, particularly erythema and pruritus. Histamine is an amine derived from histidine, present in animal tissue. Histamine is a chemical mediator of phenomena such as gastric secretions, allergies, etc. A chemical mediator should be understood to mean a substance released by a cell and involved in a process in the organism (nerve conduction, inflammation). Histamine is released in the organism from mastocytes, which are connective tissue cells which secrete chemical substances participating in immune reactions and blood coagulation, and are involved in allergic phenomena. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of histamine as a drug delivery enhancing compound for use in transmucosal or transdermal delivery Inventor(s): Pinsker, Judy Senior; (San Diego, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030143195 Date filed: January 30, 2002 Abstract: A transmucosally administerable composition with enhanced penetration comprising: about 0.001% to about 2.5% of a delivery agent selected from the group consisting of histamine, histamine dihydrochloride, histamine phosphate, a pharmaceutically acceptable salt thereof, other histamine-receptor agonists, about 0.2% to about 75% of a pharmaceutically active medicament, about 0% to about 99.8% of solvent, and about 0% to about 15% of a gelling agent. Excerpt(s): This application claims the benefit of priority from PCT/US00/20757, filed Jul. 28, 2000, published under PCT Article 21(2) in English and which claims the benefit of priority from Provisional Application No. 60/146,641, each of which is hereby incorporated by reference in their entirety. The disclosed invention relates to compositions and methods for enhancing delivery of a pharmaceutical or therapeutic

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agent to a subject. Specifically, the disclosed invention includes methods and compositions for augmented transmucosal delivery of drugs and vaccines. Various types of drug delivery systems are well known in the prior art. Possibly the most common of these systems is an intravenous drip system for the delivery of drugs to bedridden patients. In one embodiment of this system, an elevated container with a valve controlling the drip rate of the drug into a tube is coupled with a needle inserted into the patient's body. With such a system, the flow rate may be controlled by means of a valve. This system presents a number of problems, not the least of which is its limitation for use only with non-ambulatory patients. Similarly, drugs may be delivered intravenously by operation of a low volume pump. However, most systems employing pumps are rather large and require a reliable source of power for proper operation. In addition, these devices are typically limited to use with bedridden patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of histamine h3 receptor inverse agonists for the control of appetite and treatment of obesity Inventor(s): Brunden, Kurt R; (Aurora, OH), Tedford, Clark E; (Russell, OH), Yates, Stephen L; (Aurora, OH) Correspondence: Wood, Phillips, Katz, Clark & Mortimer; 500 W. Madison Street; Suite 3800; Chicago; IL; 60661; US Patent Application Number: 20040006120 Date filed: July 14, 2003 Abstract: A method for the use of histamine II.sub.3 receptor inverse agonists in the regulation of appetite and treatment of obesity is disclosed. Presently preferred inverse agonists are imidiazole derivatives. Excerpt(s): The present invention is directed to a method for the use of histamine H.sub.3 receptor inverse agonists in the regulation of appetite and treatment of obesity. Presently preferred inverse agonists are imidazole derivatives. Obesity can be described as a state of excessive accumulation of body fat and is widely considered to be a major public health problem, associated with substantially increased morbidity and mortality, as well as psychological problems, reduced economic achievement and discrimination. Examples of health problems thought to be caused or exacerbated by obesity include coronary heart disease, stroke, obstructive sleep apnea, diabetes mellitus, gout, hyperlipidemia, osteoarthritis, reduced fertility, impaired psychosocial function, reduced physical agility and increased risk of accidents, and impaired obstetrical performance. Causes of obesity remain unclear. However, whether obesity is of genetic origin or is promoted by a genotype-environment interaction, or both, it is evident that energy intake must have exceeded metabolic and physical (work) energy expenditure for there to have been surplus energy available for fat deposition. Considerable uncertainty remains concerning the relative importance of different mechanisms in achieving this positive energy balance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of histamine to treat liver disease Inventor(s): Gehlsen, Kurt R.; (Encinitas, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030091553 Date filed: October 11, 2002 Abstract: The disclosure relates to methods for treating and/or preventing hepatic tissue and cell damage caused by reactive oxygen species in mammals. More specifically, the disclosure relates to the prevention and/or reduction of hepatic tissue and cell damage through the administration of histamine and histamine agonists. Excerpt(s): This application claims priority to U.S. Provisional Application Ser. No. 60/343,628, filed on Oct. 19, 2001, and U.S. Provisional Application Ser. No. 60/340,011, filed on Oct. 30, 2001. The entire contents of these provisional applications are hereby incorporated by reference in their entireties. The disclosure below relates to methods for treating and/or preventing hepatic tissue and cell damage caused by reactive oxygen species in mammals. More specifically, the disclosure relates to the prevention and/or reduction and/or reversal of hepatic tissue and cell damage through the administration of histamine and histamine-related compounds. Oxidative stress, i.e. toxicity inflicted by reactive oxygen species (ROS), is being recognized as a systemic phenomenon in liver disease, whose extent appears to correlate with the severity and stage of disease. The mechanism of action associated with the cellular damage caused by oxidative stress has been implicated in a number of diseases including hepatitis and relates to direct damage of hepatic cells. One author has examined a role for oxidative stress in the development of the hyperdynamic circulation in portal hypertension. Bomzon and Ljubuncic have indicated, however, that it is premature to conclude that oxidative stress per se impacts at least vascular smooth muscle cell function in liver disease. Pharmacol Ther., 89(3):295308 (2001). 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 histamines, 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 “histamines” (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 histamines. You can also use this procedure to view pending patent applications concerning histamines. 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 4. BOOKS ON HISTAMINES Overview This chapter provides bibliographic book references relating to histamines. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on histamines include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “histamines” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “histamines” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “histamines” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Maslinski Histamine by MASLINSKI *HIST; ISBN: 0470618736; http://www.amazon.com/exec/obidos/ASIN/0470618736/icongroupinterna

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XIX Meeting of the European Histamine Research Society by European Histamine Society; ISBN: 9517804989; http://www.amazon.com/exec/obidos/ASIN/9517804989/icongroupinterna

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CHAPTER 5. PERIODICALS AND NEWS ON HISTAMINES Overview In this chapter, we suggest a number of news sources and present various periodicals that cover histamines.

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

Abbott working on more monoclonal antibodies, histamine and nicotinic drugs Source: Reuters Industry Breifing Date: February 17, 2003

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Influenza infection linked to increased histamine production Source: Reuters Medical News Date: November 13, 2001

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Maxim sued by investors for misrepresentation of Maxamine efficacy Source: Reuters Industry Breifing Date: December 21, 2000

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FDA advisers reject histamine dihydrochloride for advanced melanoma Source: Reuters Medical News Date: December 13, 2000

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Maxim's Maxamine metastatic melanoma therapy granted priory review Source: Reuters Industry Breifing Date: September 08, 2000 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 “histamines” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “histamines” (or synonyms). If you know the name of a company that is relevant to histamines, 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/.

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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 “histamines” (or synonyms).

Academic Periodicals covering Histamines Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to histamines. In addition to these sources, you can search for articles covering histamines 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 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for histamines. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with histamines. 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 histamines: Antihistamines •

Systemic - U.S. Brands: Alavert; Allegra; Aller-Chlor; AllerMax Caplets; Allermed; Atarax; Banophen; Banophen Caplets; Benadryl; Benadryl Allergy; Bromphen; Calm X; Chlo-Amine; Chlorate; Chlor-Trimeton; Chlor-Trimeton Allergy; Chlor-Trimeton Repetabs; Clarinex; Claritin; Claritin Reditabs; Compoz; Contac 12 Hour Allergy; Cophene-B; Dexchlor; Dimetapp Allergy Liqui-Gels; Dinate; Diphen Cough; Diphenhist; Diphenhist Captabs; Dormarex 2; Dramamine; Dramanate; Genahist; Gen-Allerate; Hydrate; Hyrexin; Hyzine-50; Nasahist B; Nervine Nighttime Sleep-Aid; Nolahist; Nytol QuickCaps; Nytol QuickGels; Optimine; PediaCare Allergy Formula; Periactin; Phenetron; Polaramine; Polaramine Repetabs; Siladryl; Sleep-Eze D; Sleep-Eze D Extra Strength; Sominex; Tavist; Tavist-1; Telachlor; Teldrin; Triptone Caplets; Twilite Caplets; Unisom Nighttime Sleep Aid; Unisom SleepGels Maximum Strength; Vistaril; Zyrtec http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202060.html

Antihistamines and Decongestants •

Systemic - U.S. Brands: Allerest Maximum Strength; Allerphed; Atrohist Pediatric; Atrohist Pediatric Suspension Dye Free; Benadryl Allergy Decongestant Liquid Medication; Brofed Liquid; Bromadrine TR; Bromfed; Bromfed-PD; Bromfenex; Bromfenex PD; Chlordrine S.R.; Chlorfed A; ChlorTrimeton 12 Hour Relief; Chlor-Trimeton 4 Hour Relief; Chlor-Trimeton AllergyD 12 Hour; Claritin-D 12 Hour; Claritin-D 24 Hour; Colfed-A; Comhist; CP Oral; Dallergy Jr; Deconamine; Deconamine SR; Deconomed SR; Dexaphen SA; Disobrom; Disophrol Chronotabs; Drixomed; Drixoral Cold and Allergy; Ed AHist; Hayfebrol; Histatab Plus; Iofed; Iofed PD; Kronofed-A Jr. Kronocaps; Kronofed-A Kronocaps; Lodrane LD; Lodrane Liquid; Mooredec; Nalex-A; ND Clear T.D.; Novafed A; PediaCare Cold Formula; Poly Hist Forte; Prometh VC Plain; Promethazine VC; Pseudo-Chlor; Rescon; Rescon JR; Rescon-ED; Respahist; Rhinosyn; Rhinosyn-PD; Rinade B.I.D.; Rondamine; Rondec; Rondec Chewable; Rondec Drops; Rondec-TR; R-Tannamine; R-Tannamine Pediatric; RTannate; Semprex-D; Silafed; Tanafed; Trinalin Repetabs; Triotann; Triotann Pediatric; Triotann-S Pediatric; Tri-Tannate; ULTRAbrom; ULTRAbrom PD http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202061.html

Antihistamines, Decongestants, and Analgesics •

Systemic - U.S. Brands: Actifed Cold & Sinus Caplets; Alka-Seltzer Plus Cold Medicine Liqui-Gels; Benadryl Allergy/Sinus Headache Caplets; Children's Tylenol Cold Multi-Symptom; Comtrex Allergy-Sinus; Comtrex Allergy-Sinus Caplets; Contac Allergy/Sinus Night Caplets; Dimetapp Cold & Fever Suspension; Dristan Cold Multi-Symptom Formula; Drixoral Allergy-Sinus; Drixoral Cold and Flu; Kolephrin Caplets; ND-Gesic; Scot-Tussin Original 5Action Cold Formula; Sinarest; Sine-Off Sinus Medicine Caplets; Singlet for Adults; TheraFlu/Flu and Cold Medicine; TheraFlu/Flu and Cold Medicine for Sore Throat; Tylenol Allergy Sinus Medication Maximum Strength Caplets; Tylenol Allergy Sinus Medication Maximum Strength Gelcaps; Tylenol Allergy Sinus Medication Maximum Strength Geltabs; Tylenol Allergy Sinus Night Time Medicine Maximum Strength Caplets; Tylenol Flu NightTime Hot Medication

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Maximum Strength; Tylenol Flu NightTime Medication Maximum Strength Gelcaps http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202062.html Antihistamines, Decongestants, and Anticholinergics •

Systemic - U.S. Brands: AH-chew; D.A. Chewable; Dallergy; Dura-Vent/DA; Extendryl; Extendryl JR; Extendryl SR; Mescolor; OMNIhist L.A.; Stahist http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202653.html

Antihistamines, Phenothiazine-derivative •

Systemic - U.S. Brands: Anergan 25; Anergan 50; Antinaus 50; Pentazine; Phenazine 25; Phenazine 50; Phencen-50; Phenergan; Phenergan Fortis; Phenergan Plain; Phenerzine; Phenoject-50; Pro-50; Promacot; Pro-Med 50; Promet; Prorex-25; Prorex-50; Prothazine; Prothazine Plain; Shogan; Tacaryl; Temaril; V-Gan-25; V-Gan-50 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202063.html

Azelastine •

Nasal - U.S. Brands: Astelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203484.html

Bismuth Subsalicylate, Metronidazole, and Tetracyclineâ€”For H. pylori •

Systemic - U.S. Brands: Helidac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203633.html

Caffeine •

Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html

Cetirizine and Pseudoephedrine •

Systemic - U.S. Brands: Zyrtec-D 12 hour http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500327.html

Cough/Cold Combinations •

Systemic - U.S. Brands: Alka-Seltzer Plus Cold and Cough; Alka-Seltzer Plus Cold and Cough Medicine Liqui-Gels; Alka-Seltzer Plus Night-Time Cold LiquiGels; Ami-Tex LA; Anatuss LA; Benylin Expectorant; Bromfed-DM; Broncholate; Carbinoxamine Compound-Drops; Cardec DM; Children's Tylenol Cold Plus Cough Multi Symptom; Co-Apap; Comtrex Daytime Maximum Strength Cold and Flu Relief; Comtrex Daytime Maximum Strength Cold, Cough, and Flu Relief; Comtrex Multi-Symptom Maximum Strength Non-Drowsy Caplets; Comtrex Nighttime Maximum Strength Cold and Flu Relief; Congestac Caplets; Contac Cold/Flu Day Caplets; Contac Severe Cold and Flu Caplets; Co-Tuss V; Deconsal II; Despec; Despec-SR Caplets; Donatussin; Donatussin DC; Duratuss; Duratuss HD; ED Tuss HC; ED-TLC; Endagen-HD; Endal Expectorant; Entex LA; Father John's Medicine Plus; Genatuss DM; GP-500; Guaifed; Guaifenex PSE 120; Guaifenex PSE 60; GuaiMAX-D; Guai-Vent/PSE; Guiatuss A.C.; Guiatuss CF; Guiatuss DAC; Guiatuss PE; Histinex HC; Histinex PV; Hycodan; Hycomine

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Compound; Hydropane; Iobid DM; Iodal HD; Iosal II; Iotussin HC; Kolephrin GG/DM; Kolephrin/DM Cough and Cold Medication; Kwelcof Liquid; Mapap Cold Formula; Marcof Expectorant; Nalex DH; Novahistine DH Liquid; Nucofed Expectorant; Nucofed Pediatric Expectorant; Nucotuss Expectorant; Nucotuss Pediatric Expectorant; Nytcold Medicine; Nytime Cold Medicine Liquid; Ornex Severe Cold No Drowsiness Caplets; PanMist-JR; PediaCare Cough-Cold; PediaCare Night Rest Cough-Cold Liquid; Pediacof Cough; Phanatuss; Phenameth VC; Phenergan VC with Codeine; Phenergan with Codeine; Phenergan with Dextromethorphan; Pneumotussin HC; Poly-Histine; Primatuss Cough Mixture 4; Primatuss Cough Mixture 4D; Profen II; Prometh VC with Codeine; Promethazine DM; Promethazine VC w/Codeine; Protuss-D; PseudoCar DM; P-V-Tussin; Quelidrine Cough; Rentamine Pediatric; Rescon-DM; Rescon-GG; Respa-1st; Respa-DM; Respaire-120 SR; Respaire-60 SR; RhinosynDM; Rhinosyn-DMX Expectorant; Rhinosyn-X; Robafen AC Cough; Robafen DAC; Robafen DM; Robitussin A-C; Robitussin Cold and Cough Liqui-Gels; Robitussin Cold, Cough and Flu Liqui-Gels; Robitussin Night Relief; Robitussin Night-Time Cold Formula; Robitussin Pediatric Cough and Cold; Robitussin Severe Congestion Liqui-Gels; Robitussin-DAC; Robitussin-DM; Robitussin-PE; Rondamine-DM Drops; Rondec-DM; Rondec-DM Drops; Ru-Tuss DE; Ru-Tuss Expectorant; Ryna-C Liquid; Ryna-CX Liquid; Rynatuss; Rynatuss Pediatric; Safe Tussin 30; Scot-Tussin DM; Scot-Tussin Senior Clear; Sildec-DM; Silexin Cough; Siltussin DM; Sinufed Timecelles; Sinutab Non-Drying No Drowsiness Liquid Caps; S-T Forte 2; Stamoist E; Statuss Green; Sudafed Children's Cold and Cough; Sudafed Children's Non-Drowsy Cold and Cough; Sudafed Cold and Cough Liquid Caps; Sudal 60/500; Syracol CF; TheraFlu Flu, Cold and Cough Medicine; TheraFlu Maximum Strength Non-Drowsy Formula Flu, Cold and Cough Medicine; TheraFlu Maximum Strength Non-Drowsy Formula Flu, Cold and Cough Medicine Caplets; TheraFlu Nighttime Maximum Strength Flu, Cold and Cough; Tolu-Sed DM; Touro DM; Touro LA Caplets; Triacin C Cough; Triafed w/Codeine; Triaminic AM Non-Drowsy Cough and Decongestant; Triaminic Night Time; Triaminic Sore Throat Formula; Tri-Tannate Plus Pediatric; Tussafed; Tussafed Drops; Tussar DM; Tussigon; Tussionex Pennkinetic; Tussi-Organidin DM NR Liquid; Tussi-Organidin DM-S NR Liquid; Tussi-Organidin NR Liquid; Tussi-Organidin-S NR Liquid; Tussirex; Tuss-LA; Tusso-DM; Tylenol Cold and Flu No Drowsiness Powder; Tylenol Cold Medication; Tylenol Cold Medication Caplets; Tylenol Cold Medication, NonDrowsy Caplets; Tylenol Cold Medication, Non-Drowsy Gelcaps; Tylenol Cold Multi-Symptom; Tylenol Maximum Strength Flu Gelcaps; Tylenol MultiSymptom Cough; Uni-tussin DM; Vanex-HD; V-Dec-M; Versacaps; Vicks 44 Cough and Cold Relief Non-Drowsy LiquiCaps; Vicks 44D Cough and Head Congestion; Vicks 44E Cough and Chest Congestion; Vicks 44M Cough, Cold and Flu Relief; Vicks Children's Cough Syrup; Vicks Children's NyQuil Cold/Cough Relief; Vicks DayQuil Multi-Symptom Cold/Flu LiquiCaps; Vicks DayQuil Multi-Symptom Cold/Flu Relief; Vicks NyQuil Hot Therapy; Vicks NyQuil Multi-Symptom Cold/Flu LiquiCaps; Vicks NyQuil Multi-Symptom Cold/Flu Relief; Vicks Pediatric 44D Cough and Head Decongestion; Vicks Pediatric 44M Multi-Symptom Cough and Cold; Vicodin Tuss; Zephrex; Zephrex-LA http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202165.html

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Cromolyn •

Nasal - U.S. Brands: Children's Nasalcrom; Nasalcrom http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202167.html

Desloratadine •

Systemic - U.S. Brands: Clarinex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500377.html

Doxepin •

Topical - U.S. Brands: Zonalon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202751.html

Emedastine •

Ophthalmic - U.S. Brands: Emadine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203486.html

Fexofenadine •

Systemic - U.S. Brands: Allegra http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203616.html

Fexofenadine and Pseudoephedrine •

Systemic - U.S. Brands: Allegra-D http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203579.html

Histamine H 2-receptor Antagonists •

Systemic - U.S. Brands: Axid; Axid AR; Mylanta AR Acid Reducer; Pepcid; Pepcid AC Acid Controller; Pepcid I.V.; Pepcid RPD; Tagamet; Tagamet HB; Zantac; Zantac EFFERdose Granules; Zantac EFFERdose Tablets http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202283.html

Ketotifen •

Ophthalmic - U.S. Brands: Zaditor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500012.html

Levocabastine •

Ophthalmic - U.S. Brands: Livostin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202715.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.

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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.

71

APPENDICES

73

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 Institute10: •

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/

10

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

•

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/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 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:12 •

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

11

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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “histamines” (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 195 3 74 1 1 274

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “histamines” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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 histamines 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 histamines. 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 histamines. 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 “histamines”:

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Asthma http://www.nlm.nih.gov/medlineplus/asthma.html Food Allergy http://www.nlm.nih.gov/medlineplus/foodallergy.html Hives http://www.nlm.nih.gov/medlineplus/hives.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.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 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 histamines. 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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to histamines. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with histamines. 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 histamines. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “histamines” (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 “histamines”. 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 “histamines” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “histamines” (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.21

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

21

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)22: •

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/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

85

•

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/

Finding Medical Libraries

87

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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

89

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).

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/

•

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

91

HISTAMINES DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the

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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] 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] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] 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] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] 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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH]

Dictionary 93

Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or

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positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [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] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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]

Dictionary 95

Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antitussive: An agent that relieves or prevents cough. [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] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apnea: A transient absence of spontaneous respiration. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord.

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Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] 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] 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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzylamines: Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group. [NIH] Bicarbonates: Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. [NIH]

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Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological 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] 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] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [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] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [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] Body Fluids: Liquid components of living organisms. [NIH]

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Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood 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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Bumetanide: A sulfamyl diuretic. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens,

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cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [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 Degranulation: The process of losing secretory granules (secretory vesicles). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [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 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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] 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] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemosis: Severe edema of the conjunctiva, least marked in the tarsal region. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of

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chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Cicatricial: Ectropion due to scar tissue on the margins or the surrounding surfaces of the eyelids. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] 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] 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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and

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leaves the body through the anus. [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] Compulsive Behavior: The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc. [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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [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]

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Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [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] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [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] 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] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary 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] 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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [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] 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]

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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. [NIH]

Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [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] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH]

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Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [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] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] 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] 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] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme

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class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drip: The continuous slow introduction of a fluid containing nutrients or drugs. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] 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

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numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its

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cytoplasm, which plays a role in hypersensitivity reactions. [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 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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] 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]

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] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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]

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Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion. [NIH] Fat: Total lipids including phospholipids. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fleas: Parasitic, blood-sucking, wingless insects comprising the order Siphonaptera. [NIH]

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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] Fold: A plication or doubling of various parts of the body. [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] 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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] 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] 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 Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH]

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Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [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] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [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]

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Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] 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] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [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] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [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.,

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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] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala, nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [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] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hetastarch: A derivative of starch used as a plasma substitute in the treatment of hemorrhage. [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]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Agonists: Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically. [NIH] Histamine dihydrochloride: A drug being studied for its ability to enhance the effectiveness of IL-2 in treating acute myeloid leukemia. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE,

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cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the 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] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ileum: The lower end of the small intestine. [NIH]

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Illusion: A false interpretation of a genuine percept. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] 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] Impromidine: A highly potent and specific histamine H2 receptor agonist. It has been used diagnostically as a gastric secretion indicator. [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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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,

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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]

Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] 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] Interindividual: Occurring between two or more individuals. [EU] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of

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digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [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] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH]

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Kinetic: Pertaining to or producing motion. [EU] Lacrimal: Pertaining to the tears. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkages: 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] Lisuride: An ergot derivative that acts as an agonist at dopamine D2 receptors, may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors. It has been used in parkinsonism but it may be hepatotoxic. It is commonly used as a research tool. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Loratadine: A second-generation histamine H1 receptor antagonist used in the treatment of

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allergic rhinitis and urticaria. Unlike most classical antihistamines it lacks central nervous system depressing effects such as drowsiness. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] 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] 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] 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] 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] 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]

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Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [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] Mesolimbic: Inner brain region governing emotion and drives. [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] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH]

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Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] 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] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH]

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Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] 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] 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] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH]

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Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neurogenic Inflammation: Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] 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] 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

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pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ophthalmic: Pertaining to the eye. [EU] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [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] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA

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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Cells: Cells in the stomach wall that make hydrochloric acid. [NIH] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [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] 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] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perennial: Lasting through the year of for several years. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the

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autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] 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] Phobias: An exaggerated and invariably pathological dread of some specific type of stimulus or situation. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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] 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]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized

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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] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma 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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH]

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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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] 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] 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] Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]

Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] 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] Prophylaxis: An attempt to prevent disease. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein 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 Conformation: The characteristic 3-dimensional shape of a protein, including the

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secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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 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 Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of

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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] Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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] Radioactive: Giving off radiation. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH]

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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] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] 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] 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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] 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] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Reversal Learning: Any situation where an animal or human is trained to respond differentially to two stimuli (e.g., approach and avoidance) under reward and punishment conditions and subsequently trained under reversed reward values (i.e., the approach which was previously rewarded is punished and vice versa). [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue

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structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [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] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs

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discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as 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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] 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] Soporific: 1. Causing or inducing profound sleep. 2. A drug or other agent which induces sleep. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] 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] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] 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

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the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] 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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] 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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic

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postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [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] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tapeworm: A flatworm that is an endoparasite and belongs to the class Cestoda. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [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] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH]

Dictionary 137

Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [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] Traction: The act of pulling. [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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

138

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Turbinates: The scroll-like bony plates with curved margins on the lateral wall of the nasal cavity. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] 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] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] 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] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH]

Dictionary 139

Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] 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] Voriconazole: A drug that treats infections caused by fungi. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [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]

Xerostomia: Decreased salivary flow. [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] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

141

INDEX 1 1-phosphate, 10, 91 A Abdomen, 91, 98, 116, 118, 134 Abdominal, 14, 91, 120, 125, 138 Abdominal Pain, 91, 138 Acetylcholine, 8, 39, 52, 91, 100, 123 Acidosis, 51, 91 Acute myeloid leukemia, 91, 113 Adenine, 91, 130 Adenosine, 52, 91, 96, 126 Adipocytes, 91, 103 Adrenal Medulla, 91, 99, 107, 108, 123 Adrenergic, 52, 53, 91, 95, 106, 108, 135, 138 Adrenergic Agonists, 53, 91 Adverse Effect, 91, 133 Aerosol, 91, 135 Aetiology, 18, 91 Affinity, 4, 12, 91, 92, 96, 134 Agonist, 7, 14, 15, 40, 50, 53, 92, 106, 115, 118 Airway, 8, 14, 30, 37, 39, 45, 92, 98, 133 Akathisia, 92, 95 Albumin, 10, 92, 127 Alertness, 4, 92 Algorithms, 92, 97 Alimentary, 92, 117, 125 Alkaline, 31, 91, 92, 93, 98 Alkaloid, 92, 121 Allergen, 8, 19, 21, 92, 133 Allergic Rhinitis, 9, 14, 20, 37, 43, 48, 92, 100, 112, 119 Allylamine, 92, 93 Alpha Particles, 92, 130 Alternative medicine, 62, 92 Ameliorating, 52, 92 Amine, 38, 46, 56, 66, 93, 113 Amino Acid Sequence, 45, 93, 94, 110 Amino Acid Substitution, 5, 93 Ammonia, 93, 138 Amnestic, 93, 120 Anabolic, 93, 108 Anaesthesia, 93, 115 Analgesic, 5, 93, 121, 124 Analog, 93, 117 Analogous, 93, 127, 137 Anaphylaxis, 12, 33, 35, 43, 49, 53, 93

Anatomical, 93, 115, 120, 132 Anemia, 31, 93, 139 Anesthesia, 18, 92, 93 Angioedema, 14, 43, 93 Anions, 92, 93, 117 Annealing, 94, 127 Anorexia, 30, 45, 94 Anoxia, 36, 51, 94 Antagonism, 9, 48, 94 Antibiotic, 32, 94, 125 Antibodies, 8, 30, 31, 40, 47, 53, 94, 112, 119, 121, 127 Antibody, 92, 94, 102, 112, 114, 115, 119, 121, 133, 134 Anticholinergic, 94, 100 Anticoagulant, 94, 128 Antiemetic, 94, 95, 105 Antigen, 40, 42, 43, 46, 47, 91, 93, 94, 102, 105, 114, 115, 119, 120, 133 Antigen-presenting cell, 94, 105 Antihistamine, 43, 94 Anti-inflammatory, 7, 53, 94, 99 Anti-Inflammatory Agents, 94, 99 Antineoplastic, 94, 111 Antioxidant, 94, 124 Antipsychotic, 12, 95, 123 Antitussive, 95, 105, 124 Antiviral, 32, 95, 116 Anus, 95, 102 Anxiety, 30, 41, 45, 92, 95, 125 Aorta, 95, 138 Aortic Aneurysm, 14, 95 Apnea, 95 Apoptosis, 36, 50, 95 Aqueous, 51, 95, 104 Arginine, 95, 123 Arrhythmia, 30, 45, 95 Arterial, 18, 21, 92, 95, 98, 114, 117, 129, 136 Arteries, 95, 97, 100, 103, 120, 122 Arterioles, 95, 97, 122 Arteriovenous, 95, 100 Artery, 95, 103, 107, 131 Articular, 14, 95, 124 Aspartate, 28, 95 Assay, 15, 24, 39, 95, 115 Astrocytes, 95, 120, 121 Atopic, 11, 19, 21, 35, 40, 47, 49, 96

142

Histamines

ATP, 36, 51, 96, 105, 111, 126, 129 Attenuated, 96, 138 Atypical, 12, 96 Autoimmune disease, 96, 121 Autonomic, 91, 95, 96, 123, 126, 135 Autonomic Nervous System, 96, 126, 135 B Bacteria, 94, 96, 107, 108, 109, 120, 130, 132, 137, 138 Bacteriophage, 96, 137 Basal Ganglia, 95, 96, 101 Basophil, 8, 16, 19, 20, 50, 96, 113 Benign, 96, 112 Benzene, 96 Benzodiazepines, 4, 96 Benzylamines, 7, 96 Bicarbonates, 32, 96 Bile, 97, 110, 111, 114, 118, 132 Bile Acids, 97, 110 Bilirubin, 92, 97, 111 Binding Sites, 5, 97 Bioavailability, 4, 97 Biochemical, 10, 97, 124, 133 Biological therapy, 97, 112 Biosynthesis, 97, 128, 133 Biotechnology, 6, 62, 75, 97 Biotransformation, 97 Bipolar Disorder, 37, 97 Bladder, 97, 121, 128, 138 Blastocyst, 97, 102, 126 Blood Coagulation, 56, 97, 98, 137 Blood Coagulation Factors, 97 Blood pressure, 18, 97, 99, 100, 114, 127, 134 Blood vessel, 97, 99, 100, 107, 117, 120, 134, 135, 137, 138 Body Fluids, 97, 134 Bone Marrow, 91, 96, 98, 112, 115, 119, 139 Bone Marrow Cells, 98, 112 Bowel, 98, 116, 117, 135, 138 Bradykinin, 98, 123, 127 Brain Ischemia, 98, 100 Brain Stem, 98, 100 Bronchi, 98, 108, 117 Bronchial, 20, 21, 34, 54, 98, 113 Bronchiectasis, 35, 49, 98 Bronchitis, 98, 101 Bronchoconstriction, 8, 53, 98 Bronchodilator, 98, 117 Bronchus, 98 Bumetanide, 18, 98

C Calcitonin, 52, 98 Calcium, 51, 98, 101, 102, 129 Calculi, 98, 111 Canonical, 8, 98 Carbohydrates, 98, 99 Carbon Dioxide, 31, 99, 104, 109, 126, 131 Carboxy, 42, 45, 46, 99 Carboxy-terminal, 45, 46, 99 Cardiac, 34, 41, 50, 51, 92, 99, 106, 108, 122 Cardiovascular, 30, 41, 45, 49, 99, 133 Cardiovascular disease, 41, 99 Cardiovascular System, 49, 99 Carotene, 99, 131 Catecholamine, 99, 106 Celecoxib, 11, 99 Cell Communication, 40, 47, 99 Cell Death, 95, 99, 122 Cell Degranulation, 53, 99 Cell Division, 96, 99, 112, 121, 127 Cell membrane, 36, 50, 99, 126 Cell Survival, 99, 112 Cellobiose, 99 Cellulose, 56, 99, 127 Central Nervous System Infections, 100, 112 Centrifugation, 100, 136 Cerebellum, 100 Cerebral, 36, 50, 96, 98, 100, 104, 108, 125 Cerebrovascular, 30, 45, 99, 100 Cerebrovascular Disorders, 30, 45, 100 Cerebrum, 100 Cetirizine, 9, 10, 21, 67, 100 Chemoreceptor, 95, 100 Chemosis, 29, 100 Chemotherapeutic agent, 32, 100 Chemotherapy, 32, 54, 100 Chloroquine, 11, 100 Cholesterol, 97, 100, 103 Cholinergic, 36, 95, 100 Chondrocytes, 14, 100 Chorea, 95, 100 Chromatin, 95, 101, 134 Chronic, 40, 47, 100, 101, 108, 116, 118, 129, 133, 135, 136, 138 Chronic Obstructive Pulmonary Disease, 40, 47, 101 Chronotropic, 54, 101 Cicatricial, 38, 101 Cirrhosis, 101, 127 CIS, 101, 131 Citric Acid, 32, 101

143

Clinical Medicine, 42, 45, 46, 101, 128 Clinical study, 101, 103 Clinical trial, 3, 75, 101, 106, 130 Cloning, 35, 40, 47, 97, 101 Cofactor, 101, 129, 137 Cognition, 8, 39, 101, 123 Colitis, 101 Collagen, 93, 101, 109, 110, 127 Collapse, 93, 101, 133 Colloidal, 92, 101, 107, 135 Colon, 17, 18, 19, 101, 116, 118, 138 Complement, 102, 111, 127, 133 Compulsive Behavior, 30, 45, 102 Computational Biology, 75, 102 Conception, 102, 109 Conduction, 56, 102 Cones, 102, 131 Congestion, 48, 54, 68, 95, 102, 108 Conjugated, 5, 102 Conjunctiva, 29, 100, 102, 117 Conjunctivitis, 19, 43, 102, 112 Connective Tissue, 56, 98, 101, 102, 103, 105, 110, 120, 126, 131, 136 Connective Tissue Cells, 56, 102, 103 Consciousness, 93, 103, 104, 105 Constipation, 30, 45, 95, 103 Constriction, 30, 45, 103, 117 Contamination, 103, 113 Contraindications, ii, 103 Controlled clinical trial, 7, 103 Convulsion, 39, 103 Coordination, 100, 103, 121 Cornea, 103, 117, 132 Coronary, 57, 99, 103, 120, 122 Coronary Arteriosclerosis, 103, 122 Coronary heart disease, 57, 99, 103 Coronary Thrombosis, 103, 120, 122 Cortex, 24, 103 Cortical, 103, 132 Cortisol, 92, 103 Cranial, 100, 103, 112, 126 Craniocerebral Trauma, 103, 112 Curative, 103, 136 Cutaneous, 21, 42, 44, 103, 117 Cyclic, 6, 38, 99, 103, 112, 123, 126 Cysteine, 52, 103, 104, 107, 135 Cystine, 103, 104 Cytokine, 16, 17, 20, 21, 104 Cytomegalovirus, 52, 104 Cytoplasm, 46, 95, 99, 104, 108, 136 Cytoskeleton, 50, 104 Cytotoxic, 32, 104

Cytotoxicity, 32, 92, 104 D Deamination, 34, 104, 121, 138 Decarboxylation, 55, 104, 113 Decidua, 104, 126 Degenerative, 104, 113, 124 Dehydration, 38, 104 Deletion, 50, 95, 104 Delirium, 95, 104 Dementia, 30, 36, 45, 95, 104, 120 Denaturation, 104, 127 Dendrites, 104, 105, 123 Dendritic, 10, 11, 12, 105, 119 Dendritic cell, 10, 11, 12, 105 Dermal, 7, 12, 105 Dermatitis, 11, 19, 31, 35, 40, 47, 49, 105 Dermis, 93, 105, 137 Deuterium, 105, 114 Diabetes Mellitus, 30, 45, 57, 105, 111, 113 Diagnostic procedure, 27, 62, 105 Diastolic, 105, 114 Diencephalon, 100, 105, 136 Digestion, 11, 92, 97, 98, 105, 117, 118, 134 Dilation, 46, 98, 105 Diphenhydramine, 30, 44, 105 Diploid, 105, 127 Direct, iii, 51, 58, 65, 99, 101, 105, 106, 114, 131, 136 Discrimination, 57, 105 Disposition, 4, 105 Dissociation, 91, 105 Distal, 105, 106, 110, 128 Diuretic, 98, 105 Dizziness, 105, 139 DNA Topoisomerase, 105, 111 Dopamine, 5, 52, 95, 106, 118, 121, 123 Dopamine Agents, 5, 106 Dose-dependent, 106, 139 Double-blind, 7, 106 Drip, 57, 106 Drug Delivery Systems, 57, 106 Drug Interactions, 70, 106 Duodenal Ulcer, 15, 106 Duodenum, 97, 106, 125, 132, 135 Dyskinesia, 30, 45, 95, 106 E Eating Disorders, 30, 37, 45, 106 Edema, 93, 100, 106, 122 Effector, 45, 46, 52, 91, 102, 106, 123, 126 Efficacy, 9, 11, 62, 106 Elective, 53, 106 Electrode, 46, 106

144

Histamines

Electrolyte, 104, 106, 134 Electrons, 94, 106, 117, 124, 130 Electrophoresis, 50, 107 Embolus, 107, 115, 117 Embryo, 97, 107, 115, 127 Emphysema, 101, 107 Encephalitis, 107, 120 Endogenous, 32, 42, 97, 106, 107, 111 Endopeptidases, 107, 128 Endorphins, 107, 123 Endothelial cell, 7, 16, 24, 107, 137 Endothelium, 107, 123 Endothelium-derived, 107, 123 Energy balance, 57, 107 Energy Intake, 57, 107 Enkephalins, 107, 123 Environmental Health, 10, 74, 76, 107 Enzymatic, 55, 93, 98, 99, 102, 107, 113, 127, 131 Eosinophil, 107, 112 Epidermal, 12, 108, 117, 119 Epidermal Growth Factor, 12, 108 Epidermis, 105, 108, 117, 128 Epinephrine, 91, 106, 108, 117, 123, 138 Epithelial, 20, 104, 108, 113 Epithelial Cells, 20, 108, 113 Epithelium, 4, 34, 107, 108 Ergot, 108, 118 Erythema, 41, 43, 56, 108, 138 Erythrocytes, 93, 98, 108, 130, 133 Esophageal, 108, 110 Esophagitis, 108, 110 Esophagus, 108, 110, 119, 126, 131, 135 Estrogens, 5, 108 Ethanol, 108, 109 Evacuation, 103, 108 Excipients, 31, 108 Excitation, 100, 108, 123 Exhaustion, 94, 109 Exogenous, 42, 97, 107, 109, 111 Extensor, 109, 129 Extracellular, 13, 51, 52, 96, 102, 109, 134 Extracellular Matrix, 102, 109 Extraction, 37, 109 Extrapyramidal, 92, 95, 106, 109 F Family Planning, 75, 109 Famotidine, 34, 109 Fat, 57, 91, 98, 99, 103, 107, 109, 118, 121, 132 Feces, 53, 103, 109, 135 Fermentation, 37, 109

Fetus, 4, 109, 126 Fibrinogen, 109, 127, 136 Fibroblasts, 103, 109 Fixation, 109, 133 Flatus, 109, 110 Fleas, 31, 109 Fluorescence, 15, 47, 110 Fold, 34, 48, 110, 120 Forearm, 97, 110 Fractionation, 110, 136 Fungi, 110, 120, 138, 139 G Gallbladder, 91, 110 Ganglia, 91, 110, 122, 126, 135 Gas, 22, 93, 99, 109, 110, 114, 122, 123, 135 Gastric, 6, 19, 28, 34, 46, 54, 56, 108, 109, 110, 113, 114, 115, 130 Gastric Acid, 34, 46, 54, 110 Gastrin, 110, 114 Gastroesophageal Reflux, 19, 110 Gastroesophageal Reflux Disease, 19, 110 Gastrointestinal, 41, 49, 98, 108, 110, 130, 133, 135 Gastrointestinal tract, 49, 108, 110, 133 Gelatin, 110, 111, 136 Gene, 13, 17, 28, 34, 35, 50, 52, 97, 110, 111, 117 Gene Library, 110, 111 Genetic Code, 110, 124 Genetic Engineering, 97, 101, 111 Genetic testing, 111, 127 Genistein, 21, 111 Genomic Library, 46, 110, 111 Genomics, 35, 111 Genotype, 5, 57, 111, 126 Germ Cells, 111, 124, 134 Gestation, 111, 126 Gestational, 4, 111 Gland, 91, 111, 125, 128, 132, 134, 135, 137 Glucose, 99, 105, 111, 113, 116 Glucose Intolerance, 105, 111 Glucuronic Acid, 5, 111 Glucuronides, 111 Glutamic Acid, 111, 123 Glycine, 93, 111, 123, 133 Glycoprotein, 4, 109, 111, 112, 137 Gout, 57, 111 Governing Board, 112, 128 Grade, 55, 112 Graft, 112, 115 Graft Rejection, 112, 115 Granulocyte, 13, 112

145

Granulocyte-Macrophage ColonyStimulating Factor, 13, 112 Growth factors, 52, 112, 120 Guanidine, 39, 112 Guanine, 29, 44, 112, 130 Guanylate Cyclase, 112, 123 H Haploid, 112, 127 Haptens, 92, 112 Hay Fever, 35, 49, 92, 112 Headache, 21, 66, 112 Headache Disorders, 112 Heart attack, 99, 113 Helminths, 113, 116 Hemoglobin, 93, 108, 113 Hemorrhage, 103, 112, 113, 135 Hepatic, 5, 16, 58, 92, 104, 113, 121 Hepatitis, 58, 113 Hepatitis A, 58, 113 Hepatocytes, 113 Hepatotoxic, 113, 118 Hepatovirus, 113 Hereditary, 53, 111, 113 Heredity, 110, 113 Hetastarch, 10, 113 Heterogeneity, 12, 92, 113 Histidine, 55, 56, 113, 114 Homologous, 114, 133, 136 Hormonal, 38, 114 Hormone, 52, 98, 103, 108, 110, 114, 116, 132, 137 Humoral, 54, 112, 114 Humour, 114 Hydrochloric Acid, 114, 125 Hydrogen, 33, 91, 93, 96, 99, 104, 105, 114, 118, 121, 123, 124, 129 Hydrogenation, 96, 114 Hydrolysis, 97, 99, 114, 127 Hydrophobic, 5, 52, 114 Hydroxyproline, 93, 101, 114 Hyperaemia, 102, 114 Hyperglycemia, 30, 45, 114 Hyperlipidemia, 57, 114 Hypersensitivity, 31, 33, 42, 43, 92, 93, 105, 108, 114, 132, 133 Hypertension, 30, 37, 45, 99, 112, 114, 127 Hyperuricemia, 111, 114 Hypnotic, 105, 114 Hypotension, 95, 114 Hypoxia, 98, 100, 104, 114 I Ileum, 54, 114

Illusion, 115, 139 Imidazole, 6, 7, 10, 21, 28, 34, 39, 53, 54, 57, 113, 115, 130 Immune response, 40, 42, 43, 47, 54, 94, 96, 112, 115, 133, 135, 139 Immune system, 94, 97, 115, 119, 121, 139 Immunization, 115, 133 Immunoassay, 18, 115 Immunoglobulin, 8, 19, 94, 115, 121 Immunologic, 115, 139 Immunology, 8, 9, 13, 14, 15, 16, 17, 18, 19, 21, 33, 91, 115 Immunosuppressive, 115 Immunosuppressive therapy, 115 Immunotherapy, 8, 54, 97, 115 Impairment, 39, 100, 104, 106, 115, 129 Impromidine, 24, 115 In vitro, 4, 14, 16, 36, 115, 127 In vivo, 4, 18, 36, 39, 115 Incision, 115, 117 Incompetence, 110, 115 Induction, 17, 18, 95, 115 Infancy, 53, 115 Infarction, 51, 98, 100, 115, 131 Infection, 37, 40, 47, 53, 61, 97, 104, 107, 112, 115, 118, 119, 125, 132, 135, 138, 139 Infestation, 31, 116 Inflammatory bowel disease, 40, 41, 47, 116 Ingestion, 116, 127 Inhalation, 14, 53, 91, 116, 127 Inotropic, 106, 116 Insomnia, 37, 116 Insulator, 116, 121 Insulin, 30, 45, 116 Insulin-dependent diabetes mellitus, 116 Interferon, 36, 49, 55, 116 Interferon-alpha, 55, 116 Interindividual, 34, 116 Interleukin-1, 41, 43, 44, 116 Interleukin-2, 116 Intestinal, 4, 99, 116 Intestine, 5, 98, 116, 118 Intracellular, 12, 29, 36, 44, 50, 51, 115, 117, 123, 132 Intracranial Embolism, 100, 117 Intracranial Embolism and Thrombosis, 100, 117 Intravenous, 18, 57, 117, 125 Intrinsic, 92, 117 Introns, 111, 117 Invasive, 14, 117

146

Histamines

Involuntary, 100, 103, 117, 122, 134 Ions, 96, 105, 106, 112, 114, 117, 129 Irritants, 53, 117 Ischemia, 36, 51, 98, 117, 131 Isoproterenol, 53, 117 J Jet lag, 37, 117 K Kb, 74, 117 Keratin, 117 Keratinocytes, 13, 117 Keratoconjunctivitis, 38, 117 Keratoconjunctivitis Sicca, 38, 117 Kinetic, 118 L Lacrimal, 117, 118 Lag, 118 Large Intestine, 117, 118, 130, 133 Latent, 118, 128 Leprosy, 7, 118 Lesion, 118, 136, 138 Lethal, 54, 118, 122 Leukocytes, 98, 116, 118 Leukopenia, 118, 139 Life cycle, 106, 110, 118 Ligament, 118, 128 Ligands, 33, 48, 118 Linkages, 113, 118, 139 Lipid, 8, 116, 118, 121, 125 Lipid Peroxidation, 118, 125 Lisuride, 7, 118 Lithium, 95, 118 Liver, 4, 5, 15, 58, 91, 92, 97, 100, 101, 104, 109, 110, 111, 112, 113, 118, 121, 127, 132, 138 Localization, 5, 16, 118 Localized, 93, 98, 109, 115, 118, 121, 126, 138 Locomotion, 118, 127 Loratadine, 21, 54, 118 Lower Esophageal Sphincter, 110, 119 Lymph, 107, 114, 119, 135 Lymphatic, 107, 116, 119, 120, 134 Lymphocyte, 94, 119 Lymphoid, 94, 119 Lymphoma, 20, 119 M Macrophage, 112, 116, 119 Malnutrition, 92, 119 Mania, 119 Manic, 37, 95, 97, 118, 119, 129 Manifest, 38, 119

Mastication, 9, 119 Mediate, 5, 51, 54, 106, 119, 130 Mediator, 14, 34, 49, 56, 116, 119, 133 Medicament, 42, 56, 119 MEDLINE, 75, 119 Melanocytes, 119 Melanoma, 62, 119 Membrane, 36, 41, 46, 50, 51, 52, 92, 96, 99, 102, 109, 119, 121, 124, 126, 131, 132, 136 Memory, 8, 37, 39, 94, 104, 119, 120 Memory Disorders, 37, 120 Meninges, 100, 103, 120 Mental, iv, 3, 74, 76, 101, 104, 105, 115, 119, 120, 129, 132 Mental Health, iv, 3, 74, 76, 120, 129 Mesenchymal, 108, 112, 120 Mesenteric, 14, 120 Mesentery, 120 Mesolimbic, 95, 120 Metabolic disorder, 111, 120 Metabolite, 16, 97, 120 Metastasis, 120 Metastatic, 62, 120 Methionine, 12, 34, 120, 135 Methyltransferase, 17, 34, 120 MI, 40, 89, 120 Microbe, 120, 137 Microbiology, 96, 120 Microglia, 96, 120, 121 Microorganism, 101, 120, 139 Migration, 40, 47, 53, 120 Mitosis, 95, 121 Modeling, 8, 121 Modification, 93, 111, 121, 130, 139 Molecular, 4, 7, 10, 19, 20, 34, 35, 40, 47, 75, 77, 97, 102, 109, 121 Molecule, 30, 45, 55, 94, 97, 102, 105, 106, 107, 108, 114, 121, 124, 130, 138 Monoamine, 28, 34, 121, 138 Monoamine Oxidase, 34, 121, 138 Monoclonal, 54, 61, 121 Monoclonal antibodies, 54, 61, 121 Monocyte, 11, 121 Morphine, 5, 121, 122, 124 Motion Sickness, 37, 121, 122 Mucins, 38, 121 Mucociliary, 121, 133 Mucosa, 6, 46, 121, 122 Mucus, 121, 132, 138 Multiple sclerosis, 40, 47, 121 Mustard Gas, 117, 122 Myasthenia, 112, 122

147

Mydriatic, 105, 122 Myelin, 121, 122 Myocardial infarction, 103, 120, 122 Myocardial Ischemia, 51, 122 Myocardium, 120, 122 N Narcolepsy, 37, 122 Narcotic, 121, 122 Nasal Cavity, 122, 138 Nausea, 94, 95, 122 Necrosis, 95, 115, 120, 122, 131 Neoplastic, 119, 122 Nerve Endings, 49, 51, 122, 136 Nerve Growth Factor, 10, 13, 122 Nervous System, 13, 30, 36, 38, 41, 45, 49, 52, 91, 96, 100, 110, 111, 119, 120, 121, 122, 123, 126, 133, 135, 136, 138 Neural, 114, 120, 121, 123 Neuroeffector Junction, 122, 123 Neurogenic Inflammation, 37, 123 Neuroleptic, 92, 95, 123 Neuromuscular, 91, 123 Neuromuscular Junction, 91, 123 Neuronal, 19, 123, 126 Neurons, 9, 30, 36, 45, 104, 106, 110, 122, 123, 135, 136 Neuropeptides, 10, 123 Neurotransmitter, 30, 34, 45, 46, 91, 93, 98, 99, 106, 111, 113, 123, 135, 138 Neutrons, 92, 123, 130 Neutrophil, 14, 123 Nitric Oxide, 21, 123 Nitrogen, 28, 33, 92, 93, 109, 123 Norepinephrine, 51, 91, 106, 123 Nuclear, 96, 107, 122, 124, 136 Nucleic acid, 28, 30, 31, 34, 35, 40, 45, 46, 47, 49, 110, 123, 124, 130, 139 Nucleus, 95, 96, 101, 103, 104, 105, 123, 124, 129, 135 O Ocular, 38, 51, 124 Ophthalmic, 19, 38, 51, 69, 124 Opiate, 121, 124 Opium, 121, 124 Opsin, 124, 131, 132 Organelles, 100, 104, 119, 124 Orthostatic, 95, 124 Osmosis, 36, 124 Osmotic, 92, 124 Osteoarthritis, 57, 124 Osteoclasts, 98, 124 Ovary, 124, 127

Oxidation, 94, 97, 104, 118, 124, 125 Oxidative Stress, 58, 124 P Palate, 125, 138 Palliative, 125, 136 Pancreas, 91, 116, 125, 132 Pancreatic, 110, 125 Pancreatic Juice, 110, 125 Panic, 30, 45, 125 Papule, 31, 125 Parasitic, 109, 113, 116, 125, 132 Parenteral, 107, 125 Parietal, 28, 125 Parietal Cells, 28, 125 Parietal Lobe, 125 Parkinsonism, 95, 118, 125 Partial remission, 125, 131 Particle, 125, 134, 137 Patch, 125, 137 Pathologic, 91, 95, 103, 114, 125, 129 Pathologic Processes, 95, 125 Pelvic, 125, 128 Penicillin, 94, 125 Pepsin, 125, 132 Peptide, 14, 53, 93, 98, 107, 117, 125, 127, 128, 129 Perennial, 48, 125 Peripheral blood, 116, 125 Peripheral Nerves, 118, 125 Peripheral Nervous System, 107, 123, 126, 128, 135 Pharmaceutical Preparations, 100, 108, 110, 126 Pharmacodynamic, 109, 126 Pharmacokinetic, 126 Pharmacologic, 93, 126, 137 Pharynx, 110, 122, 126 Phenotype, 35, 126 Phobias, 30, 45, 126 Phosphodiesterase, 52, 126 Phospholipids, 109, 126 Phosphorus, 98, 126 Physiologic, 92, 97, 126, 130 Pigment, 97, 119, 126 Placenta, 4, 126 Plague, 31, 126 Plants, 41, 92, 99, 111, 123, 126, 127, 137 Plasma, 10, 18, 50, 51, 92, 94, 98, 99, 109, 110, 111, 113, 127, 129, 133 Plasma cells, 94, 127 Plasma protein, 92, 127, 129 Platelet Aggregation, 123, 127

148

Histamines

Platelets, 99, 123, 127, 133, 137 Pneumonia, 103, 127 Poisoning, 11, 104, 108, 122, 127 Pollen, 35, 37, 48, 49, 100, 127 Polyarthritis, 117, 127 Polymerase, 28, 127 Polymerase Chain Reaction, 28, 127 Polymorphic, 5, 28, 100, 127 Polymorphism, 34, 127 Polypeptide, 46, 93, 99, 101, 108, 109, 127, 129, 139 Polysaccharide, 94, 99, 127 Portal Hypertension, 58, 127 Posterior, 100, 125, 128, 132, 138 Postsynaptic, 36, 123, 128 Post-synaptic, 128 Post-synaptic, 136 Potentiates, 116, 128 Practice Guidelines, 76, 128 Precursor, 106, 107, 123, 128, 129, 138 Predisposition, 50, 128 Pregnancy Maintenance, 108, 128 Presynaptic, 30, 36, 45, 122, 123, 128 Presynaptic Terminals, 122, 128 Prickle, 117, 128 Probe, 112, 128 Progressive, 101, 104, 122, 124, 128 Projection, 123, 128 Prophylaxis, 14, 43, 128 Prostate, 30, 45, 128 Protease, 4, 18, 128 Protease Inhibitors, 4, 18, 128 Protein C, 28, 29, 44, 50, 52, 92, 93, 96, 111, 117, 128, 138 Protein Conformation, 93, 117, 128 Protein S, 5, 52, 97, 110, 129 Protein-Tyrosine Kinase, 111, 129 Prothrombin, 129, 136 Protons, 92, 114, 129, 130 Protozoa, 120, 129, 138 Pruritus, 11, 41, 43, 56, 105, 129 Psoriasis, 40, 47, 122, 129 Psychiatric, 41, 129 Psychiatry, 109, 129 Psychic, 120, 129, 132 Psychosis, 95, 111, 129 Public Health, 57, 76, 129 Public Policy, 75, 129 Publishing, 6, 33, 129 Pulmonary, 97, 130, 138 Pulmonary Artery, 97, 130, 138 Punishment, 130, 131

Pupil, 103, 105, 122, 130 Purines, 130, 133 Pyrimidines, 130, 133 Q Quality of Life, 4, 130 R Race, 10, 120, 130 Racemic, 10, 130 Radiation, 54, 110, 130 Radioactive, 114, 121, 124, 130 Randomized, 106, 130 Ranitidine, 11, 30, 34, 44, 130 Reactive Oxygen Species, 58, 130 Reagent, 22, 47, 114, 130 Recombinant, 15, 17, 29, 30, 35, 40, 44, 45, 47, 130, 138 Rectum, 95, 101, 109, 110, 116, 118, 128, 130 Recurrence, 97, 130 Red blood cells, 34, 108, 130 Refer, 1, 102, 105, 107, 109, 110, 118, 123, 129, 131 Reflux, 110, 131 Refractory, 15, 131 Regimen, 106, 131 Regurgitation, 110, 131 Remission, 20, 97, 130, 131 Reperfusion, 37, 131 Reperfusion Injury, 131 Resection, 19, 131 Respiration, 95, 99, 100, 131 Retina, 102, 131, 132 Retinal, 17, 131, 132 Retinol, 131, 132 Reversal Learning, 39, 131 Rheumatism, 131, 132 Rheumatoid, 40, 47, 53, 100, 132 Rheumatoid arthritis, 40, 47, 53, 100, 132 Rhinitis, 33, 35, 37, 48, 49, 132 Rhinorrhea, 48, 132 Rhodopsin, 124, 131, 132 Ribose, 91, 132 Rickettsiae, 132, 138 Rods, 131, 132 S Salivary, 104, 132, 135, 139 Salivary glands, 104, 132 Schizophrenia, 30, 37, 45, 120, 132 Sclera, 102, 132 Sclerosis, 121, 132 Screening, 15, 40, 47, 101, 132 Sebaceous, 105, 117, 132

149

Sebaceous gland, 105, 117, 132 Secretin, 30, 45, 132 Secretory, 41, 99, 123, 132 Secretory Vesicles, 99, 132 Sedative, 43, 105, 132 Seizures, 39, 104, 132 Semen, 128, 132 Seminiferous tubule, 133, 134 Senile, 30, 45, 133 Sensitization, 19, 133 Sequencing, 28, 35, 127, 133 Serine, 28, 107, 133 Serologic, 115, 133 Serotonin, 95, 118, 121, 123, 133 Serum, 92, 102, 133 Sex Characteristics, 108, 133 Shock, 93, 133 Side effect, 65, 91, 92, 95, 97, 100, 114, 133, 137 Signs and Symptoms, 131, 133 Sinusitis, 43, 133 Skeletal, 117, 133 Skin test, 14, 133 Sleep apnea, 57, 133 Small intestine, 106, 114, 117, 133 Smooth muscle, 36, 41, 46, 54, 58, 92, 98, 103, 113, 121, 134, 135 Sneezing, 48, 134 Social Environment, 130, 134 Sodium, 18, 50, 51, 111, 134 Solvent, 56, 96, 108, 124, 134 Somatic, 114, 121, 126, 134 Soporific, 4, 134 Sound wave, 102, 134 Specialist, 81, 105, 134 Species, 46, 58, 108, 113, 120, 121, 125, 130, 134, 135, 139 Specificity, 92, 107, 134 Sperm, 127, 133, 134 Spermatozoa, 17, 133, 134 Spinal cord, 95, 98, 100, 120, 122, 125, 126, 134, 135 Spinous, 108, 117, 134 Spleen, 104, 119, 134 Stimulant, 67, 113, 117, 134 Stimulus, 106, 108, 118, 123, 126, 130, 134, 136 Stomach, 30, 41, 44, 91, 108, 110, 114, 119, 122, 125, 126, 131, 132, 133, 134 Stool, 101, 118, 135 Strand, 127, 135

Stress, 30, 45, 58, 96, 99, 103, 122, 124, 128, 132, 135, 138 Stroke, 40, 47, 57, 74, 99, 135 Structure-Activity Relationship, 20, 135 Subacute, 116, 133, 135 Subarachnoid, 112, 135 Subclinical, 116, 132, 135 Subcutaneous, 91, 93, 106, 125, 135 Submaxillary, 108, 135 Subspecies, 134, 135 Substance P, 120, 132, 135 Substrate, 4, 5, 135, 138 Sulfur, 33, 120, 135 Suppression, 18, 42, 135, 139 Suspensions, 46, 135, 138 Sympathetic Nervous System, 54, 96, 135, 136 Sympathomimetic, 106, 108, 117, 124, 135, 138 Symphysis, 128, 136 Symptomatic, 37, 53, 136 Synapse, 91, 123, 128, 136, 137 Synaptic, 123, 136 Synaptosomes, 36, 136 Synergistic, 32, 54, 136 Systemic, 58, 66, 67, 69, 93, 95, 97, 98, 100, 104, 108, 116, 136 Systemic lupus erythematosus, 100, 136 Systemic therapy, 100, 136 Systolic, 114, 136 T Tapeworm, 31, 136 Tardive, 30, 45, 95, 136 Tear Gases, 117, 136 Thalamus, 30, 105, 136 Therapeutics, 7, 12, 13, 17, 70, 121, 136 Thermal, 105, 123, 127, 136 Threonine, 28, 133, 136 Threshold, 39, 114, 136 Thrombin, 24, 52, 109, 127, 128, 129, 136, 137 Thrombomodulin, 128, 137 Thrombosis, 117, 129, 135, 137 Thrombus, 103, 115, 122, 127, 137 Thyroid, 98, 137, 138 Thyroxine, 92, 137 Ticks, 116, 137 Topical, 38, 41, 44, 56, 69, 108, 137 Torsion, 115, 137 Toxic, iv, 54, 96, 104, 113, 137, 139 Toxicity, 58, 106, 137 Toxicokinetics, 137

150

Histamines

Toxicology, 9, 76, 137 Toxins, 94, 107, 111, 115, 121, 137 Traction, 14, 137 Transdermal, 56, 137 Transduction, 45, 46, 52, 137 Transfection, 97, 137 Translation, 93, 137 Transmitter, 29, 44, 91, 96, 106, 119, 123, 137, 138 Trigger zone, 95, 137 Tunica, 121, 137 Turbinates, 16, 138 Tyramine, 121, 138 Tyrosine, 106, 129, 138 U Ulcer, 106, 138 Ulcerative colitis, 41, 116, 138 Urea, 39, 138 Urethra, 128, 138 Uric, 111, 114, 130, 138 Urinary, 52, 98, 138 Urine, 97, 105, 108, 111, 112, 138 Urticaria, 33, 35, 43, 49, 93, 100, 119, 138 Uvula, 14, 138 V Vaccines, 57, 138, 139

Vascular, 36, 46, 53, 58, 92, 93, 100, 105, 107, 113, 115, 116, 123, 126, 137, 138 Vasculitis, 100, 138 Vasodilatation, 29, 54, 138 Vasodilator, 98, 106, 113, 138 Vector, 137, 138 Vein, 24, 95, 117, 124, 127, 138 Venous, 95, 117, 129, 138 Ventricle, 130, 136, 138 Vertigo, 37, 139 Veterinary Medicine, 75, 139 Viral, 53, 107, 137, 139 Virulence, 96, 137, 139 Virus, 53, 96, 100, 111, 116, 137, 139 Vitro, 36, 139 Vivo, 4, 39, 139 Voriconazole, 13, 139 W Wakefulness, 4, 104, 139 White blood cell, 46, 91, 94, 96, 112, 118, 119, 121, 123, 127, 139 X Xerostomia, 117, 139 Y Yeasts, 110, 126, 139 Z Zidovudine, 5, 139 Zymogen, 128, 139

151

152

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