ALDOSTERONE 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., 1960Aldosterone: 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: 0-497-00042-3 1. Aldosterone-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on aldosterone. 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 ALDOSTERONE .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Aldosterone ................................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 73 CHAPTER 2. NUTRITION AND ALDOSTERONE .............................................................................. 121 Overview.................................................................................................................................... 121 Finding Nutrition Studies on Aldosterone ................................................................................ 121 Federal Resources on Nutrition ................................................................................................. 124 Additional Web Resources ......................................................................................................... 124 CHAPTER 3. ALTERNATIVE MEDICINE AND ALDOSTERONE ........................................................ 127 Overview.................................................................................................................................... 127 National Center for Complementary and Alternative Medicine................................................ 127 Additional Web Resources ......................................................................................................... 136 General References ..................................................................................................................... 137 CHAPTER 4. DISSERTATIONS ON ALDOSTERONE .......................................................................... 139 Overview.................................................................................................................................... 139 Dissertations on Aldosterone ..................................................................................................... 139 Keeping Current ........................................................................................................................ 140 CHAPTER 5. PATENTS ON ALDOSTERONE .................................................................................... 141 Overview.................................................................................................................................... 141 Patents on Aldosterone .............................................................................................................. 141 Patent Applications on Aldosterone .......................................................................................... 147 Keeping Current ........................................................................................................................ 156 CHAPTER 6. BOOKS ON ALDOSTERONE ........................................................................................ 157 Overview.................................................................................................................................... 157 Book Summaries: Federal Agencies............................................................................................ 157 Book Summaries: Online Booksellers......................................................................................... 158 Chapters on Aldosterone ............................................................................................................ 159 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 167 Overview.................................................................................................................................... 167 NIH Guidelines.......................................................................................................................... 167 NIH Databases........................................................................................................................... 169 Other Commercial Databases..................................................................................................... 171 APPENDIX B. PATIENT RESOURCES ............................................................................................... 173 Overview.................................................................................................................................... 173 Patient Guideline Sources.......................................................................................................... 173 Finding Associations.................................................................................................................. 175 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 177 Overview.................................................................................................................................... 177 Preparation................................................................................................................................. 177 Finding a Local Medical Library................................................................................................ 177 Medical Libraries in the U.S. and Canada ................................................................................. 177 ONLINE GLOSSARIES................................................................................................................ 183 Online Dictionary Directories ................................................................................................... 184 ALDOSTERONE DICTIONARY................................................................................................ 187
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INDEX .............................................................................................................................................. 255
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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 aldosterone 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 aldosterone, 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 aldosterone, 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 aldosterone. 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 aldosterone, 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 aldosterone. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON ALDOSTERONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on aldosterone.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and aldosterone, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “aldosterone” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Diabetes Mellitus: Nephropathy and Hypertension Source: Clinical Diabetes. 14(4): 91-94. July-August 1996. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. Summary: Diabetes and hypertension are interrelated diseases that, independently and in concert, lead to nephropathy. This article examines this occurrence, with an emphasis on prevention. Topics include the prevalence of hypertension in patients with diabetes or impaired glucose tolerance; the etiology and clinical course of hypertension; the role of genetics in both diabetes and hypertension; the renin-angiotensin aldosterone system; differences between IDDM and NIDDM in rates of hypertension and nephropathy; how hyperglycemia contributes to the development and progression of diabetic
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nephropathy; other risk factors, including age, duration of diabetes, gender, lipid levels, and smoking; the diagnosis and natural history of diabetic nephropathy; and the treatment strategies of dialysis and transplantation. The article concludes with a review of the preventive measures, including blood glucose control, protein intake and lifestyle changes, and blood pressure control, that can delay the development or progression of diabetic nephropathy. 18 references. •
Endocrinology and Pathophysiology of Alcoholic Cirrhosis and Functional Renal Failure: A Review Source: Journal of the National Medical Association. 84(2): 153-162. February 1992. Summary: In this article, the pathophysiology and characteristics of decompensated alcoholic cirrhosis and functional renal failure are reviewed. The review is restricted to alcoholic cirrhosis, because most cases of functional renal failure in the United States occur in the setting of alcoholic cirrhosis, which is also the most common cause of ascites in North America and Europe. The authors discuss the endocrinological character of decompensated cirrhosis, noting that it is often seen with abnormal hormone concentrations, including elevations in renin activity, arginine vasopressin, and aldosterone, and with alterations in prostaglandin secretion and release. When decompensated cirrhosis no longer appears to be responsive to available treatment regimens, or when ascites persists despite sodium restriction and use of maximal diuretic therapy, the fluid and electrolyte abnormality has apparently evolved into functional renal failure. This condition may be relatively stable or may progress rapidly downhill and be recognizable as hepatorenal syndrome. 127 references.
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Pathology of Progressive Nephropathies Source: Current Opinion in Nephrology and Hypertension. 9(3): 241-246. May 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: In this review article, the role of cell cycle regulatory proteins in the progression of kidney disease is elucidated. Human renal biopsy data show reduction and even regression of structural injury can be achieved with interventions that reestablish the balance of the extracellular matrix (ECM) metabolism. Data from recent studies implicate new mechanisms of the renin aldosterone angiotensin system in progressive injuries, including immune modulation and a direct effect of aldosterone on progression. Advances in understanding of the cell biology of the kidney glomerulus, and in particular the GVEC (glomerular visceral epithelial cell), point to a key role of the cell cycle regulatory proteins p21 and p27 in response to injury. Regression of injury has even been demonstrated in human diabetic nephropathy (kidney disease associated with diabetes mellitus). The authors note that future research will need to elucidate which findings from animal models are relevant to human diseases, and this may lead to optimal therapies to slow progression and perhaps even induce regression of sclerosis (tissue hardening). 59 references (46 annotated).
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ACE Inhibition or Angiotensin Receptor Blockade: Impact on Potassium in Renal Failure Source: Kidney International. 58(5): 2084-2092. November 2000.
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Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: Inhibition of the renin angiotensin system is known to raise serum potassium (K+) levels in patients with renal insufficiency or diabetes. This study evaluates the comparative effects of an angiotensin converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum K+ in people with renal (kidney) insufficiency. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasians, mean age 56 years plus or minus 2 years) participated in the double crossover study. For the total group serum potassium level changes were not significantly different between the lisinopril (an ACE inhibitor) and valsartan (an ARB) treatments. The subgroup with glomerular filtration rate (a measure of kidney function) values of less than 60 milliliters per minute per 1.73 m-squared who received lisinopril demonstrated significant increases in serum potassium above the mean baseline. This increase in serum potassium was also accompanied by a decrease in plasma aldosterone. The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum potassium; this represents a 43 percent lower value when compared with the change in those who received lisinopril. The authors conclude that, in the presence of renal insufficiency, the ARB valsartan did not raise serum potassium to the same degree as the ACE inhibitor lisinopril. 4 figures. 3 tables. 29 references. •
Hyperkalemia in the Elderly Source: American Journal of Kidney Diseases. 16(4): 296-299. October 1990. Summary: Physiologic and pathologic events that occur in patients as they grow older may result in distal renal tubular dysfunction, as well as decreased levels of plasma renin activity and plasma aldosterone. Such alterations result in a tendency toward hyperkalemia. This article discusses hyperkalemia in the elderly. A syndrome termed hyporeninemic hypoaldosteronism, associated with hyperkalemia, has been frequently described in elderly patients. The common occurrence of hyperkalemia in the elderly may be aggravated by the use of drugs that either further suppress renin and/or aldosterone or interfere with distal tubular potassium excretion. Some patients with hyporeninemic hypoaldosteronism respond to diuretic therapy. The recognition or the possible development of severe hyperkalemia in the elderly patient may avoid serious and even fatal complications of this electrolyte disorder. 5 tables. 23 references. (AA).
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Angiotensin-Converting Enzyme Inhibitor-Associated Elevations in Serum Creatinine: Is This a Cause for Concern? Source: Archives of Internal Medicine. 160(5): 685-693. March 13, 2000. Contact: Available from American Medical Association. Subscriber Services Center, P.O. Box 10946, Chicago, IL 60610-0946. (800) 262-2350. Fax (312) 464-5831. E-mail:
[email protected]. Summary: Reducing the actions of the renin angiotensin aldosterone system with angiotensin converting enzyme (ACE) inhibitors slows nephropathy (kidney disease) progression in patients with or without diabetes. This article reports on a study undertaken to determine whether limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACE inhibitor or angiotensin receptor blocker use, results in long term protection against decline in renal (kidney) function in patients with renal insufficiency. The authors reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double blinded,
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and placebo controlled, with the remainder being smaller randomized studies with a minimum 2 year followup on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACE inhibitor with a serum creatinine level of 124 or greater demonstrated a 55 to 75 percent risk reduction in renal disease progression, compared with those with normal renal function randomized to an ACE inhibitor. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACE inhibitor. The authors conclude that in both diabetic and nondiabetic renal disease, if an elevation in serum creatinine occurs within the first 2 months of ACE inhibitor therapy, it stabilizes quickly, does not progressively worsen, and is strongly associated with long term preservation of renal function. Withdrawal of ACE inhibitor use in these patients should occur only when the rise of creatinine exceeds 30 percent above baseline within the first 2 months of ACE inhibitor use, or if hyperkalemia (excessive potassium in the blood) develops. 7 figures. 1 table. 53 references. •
Association of Hypokalemia, Aldosteronism, and Renal Cysts Source: New England Journal of Medicine. 322(6): 345-351. February 8, 1990. Summary: The recognition of renal cysts in two patients with chronic hypokalemia and the renal effects of hypokalemia in certain species of animals prompted this study of the possible association of hypokalemia and renal cysts in patients with primary aldosteronism or primary renal potassium wasting. Using CT scans, the authors studied 55 patients with primary aldosteronism, of whom 24 had cysts (44 percent). The cysts were more frequent in patients with adrenal tumors than in those with idiopathic adrenal hyperplasia. 16 of the 26 patients with tumors (62 percent) had renal cysts, which were often multiple and located in the medulla. Lower plasma potassium levels and higher serum aldosterone levels, urinary aldosterone excretion, and plasma renin activity were correlated with the extent of the cystic disease. Sequential observations indicated that prolonged hypokalemia can be accompanied by the development of renal scarring and that the site and number of cysts can decrease markedly in some patients after the removal of an adrenal adenoma. The association of hypokalemia, aldosteronism, and renal cysts was also supported by the finding of multiple medullary cysts in two patients with primary renal potassium wasting. The authors conclude that chronic hypokalemia is accompanied by enhanced renal cystogenesis and may lead to interstitial scarring and renal insufficiency. Renal cysts are thus dynamic structures whose growth can be influenced by hormonal or pharmacologic interventions. 30 references. (AA).
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Nocturnal Polyuria in Older People: Pathophysiology and Clinical Implications Source: JAGS. Journal of the American Geriatrics Society. 48(10): 1321-1329. October 2000. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423. Summary: This article reports on a literature review that covered the physiological changes of aging that affect the systems involved in urine formation and that considered how these changes interact with changes in bladder function, thereby leading to the onset of nocturnal polyuria (excessive urination) with associated urinary frequency,
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nocturia (urinating at night), and incontinence (involuntary loss of urine). Based on this information, the author presents data on the effectiveness of pharmacological interventions (drug therapy) which reduce the rate of urine formation and, thus, can be of benefit in reducing symptoms, especially during the nighttime. Peer reviewed journal articles were identified by MEDLINE search and by review of the literature. As a consequence of age associated diminished renal (kidney) concentrating capacity, diminished sodium conserving ability, loss of the circadian rhythm of antidiuretic hormone secretion, decreased secretion of renin angiotensin aldosterone, and increased secretion of atrial natriuretic hormone, there is an age related alteration in the circadian rhythm of water excretion, leading to increased nighttime urine production in older people. The interaction of nocturnal polyuria with age related diminution in functional bladder volume and detrusor instability results in the symptoms of urinary frequency, nocturia, and, in some persons, incontinence. The additional impact of Alzheimer's disease on these physiological and aging changes, as well as on a diminished perception of bladder fullness, leads to an even greater risk of urinary incontinence in these patients. Treatment of nocturnal polyuria with the antidiuretic hormone analog, DDAVP (desmopressin), can result in decreased nocturnal urine production with improvement in symptoms of frequency, nocturia, and incontinence. 4 tables. 104 references. •
Renal Parenchymal Disease and Hypertension Source: Seminars in Nephrology. 15(2): 138-151. March 1995. Contact: Available from W.B. Saunders Company, Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: This review article explores the interrelationship of renal parenchymal disease and hypertension. Topics include pathophysiology and pathogenesis; sodium balance; digitalis like factor (DLF); the renin angiotensin aldosterone system; renal prostaglandins; the renal kallikrein system; endothelin (ET); endothelium derived relaxing factor; nitric oxide (NO); nephron dosing, hypertension, and renal injury; treatment considerations, including protein and sodium restriction, diuretics, and treatment for refractory hypertension; and strategies to retard the progression of renal disease. The authors conclude that renal parenchymal hypertension constitutes a 'fascinating constellation' with numerous and diverse causes and an incompletely defined pathophysiology. 123 references.
Federally Funded Research on Aldosterone The U.S. Government supports a variety of research studies relating to aldosterone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions.
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to aldosterone. 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 aldosterone. The following is typical of the type of information found when searching the CRISP database for aldosterone: •
Project Title: DEFERENS
ACIDIFICATION
MECHANISM
IN
THE
EPIDIDYMIS/VAS
Principal Investigator & Institution: Breton, Sylvie; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 31-MAR-2007 Summary: Description (provided by applicant) The absorptive and secretory capacity of epithelial cells of the epididymis and vas deferens (VD) creates the appropriate environment for spermatozoa as they mature and are stored. The lumen of these organs is maintained acidic compared to blood and has a low bicarbonate concentration. These factors are involved in sperm maturation and the maintenance of sperm in a quiescent state during their storage period. We propose that Na/H exchanger-rich (principal) cells actively absorb bicarbonate in the proximal regions of the epididymis and that H+ATPase-rich (clear) cells are responsible for net proton secretion in the distal epididymis and vas deferens. Specific aim 1 will characterize the acid/base transporters involved in luminal acidification in the initial segments of the epididymis, and in the cauda epididymis and VD (H+ATPase, Na+/H+ exchanger, NBC1, NBC3, AE2). Specific aim 2 will examine the molecular mechanisms responsible for the regulation of proton secretion and bicarbonate reabsorption. Specifically, we will study the role of SNARE proteins, the actin-severing protein, gelsolin, and the newly identified "bicarbonate sensor" adenynyl cyclase, sAC, in the recycling of H+ATPase-containing vesicles. The role of the Na/H exchange regulatory factor, NHE-RF, and sAC will also be examined in bicarbonate reabsorption, possibly via CAMP-modulation of the Na/H exchanger. Specific aim 3 will examine the hormonal regulation of luminal acidification in the epididymis and VD. Short-term and long-term regulation by steroid hormones (aldosterone, testosterone, estrogens) and by angiotensin II will be studied. These studies will be carried out using a multidisciplinary approach (proton-selective selfreferencing extracellular electrode, intracellular pH measurements, light microscopy and EM immunocytochemistry, western blotting, in situ hybridization, laser capture microdissection and real time RT-PCR), and will help to unravel the mechanisms underlying acid/base transport in the organs where spermatozoa mature and are stored. The ultimate aim of this application is to better understand the physiology and pathophysiology of male fertility, because a defect in the acidification capacity of the epididymis and vas deferens might result in deficient sperm maturation and motility, leading to lower fertility. Project 12 will benefit from constant interaction with the other projects of this Program, especially Projects 7 and 9, which propose to characterize AQP2 recycling, and the mechanisms for acidification-dependent endosomal regulation, respectively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AC-SDKP IN TARGET ORGAN DAMAGE IN HYPERTENSION Principal Investigator & Institution: Carretero, Oscar A.; Division Head; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant) Hypertension is a cardiovascular risk factor that often leads to target organ damage. Angiotensin-converting enzyme inhibitors (ACEi) significantly reduce cardiovascular events, especially in high-risk patients. The effects of ACEi are mediated by inhibition of both the conversion of Ang I to Ang II and kinin degradation. We have evidence that in hypertension another peptide hydrolyzed by ACE, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), prevents and reverses cardiac fibrosis without altering blood pressure (BP) or cardiocyte hypertrophy. This is the first demonstration that administration of Ac-SDKP has an effect on cardiac fibrosis; however, we do not know whether Ac-SDKP has a physiological role, the mechanism by which it inhibits fibrosis or whether it contributes to the cardiovascular protective effects of ACEi. In this project we propose to test the general hypothesis that in hypertension cardiac fibrosis is the result of an alteration of the balance between pro-fibrotic and proinflammatory vs anti-fibrotic and anti-inflammatory systems. Ac-SDKP alters this balance in favor of the latter, reversing fibrosis (an important component of target organ damage) and improving cardiac function. The mechanisms by which Ac-SDKP antagonizes pro-fibrotic stimuli are: a) directly by inhibiting fibroblast proliferation and collagen synthesis and b) indirectly by acting as an anti-inflammatory cytokine, thus inhibiting production of TGF beta 1 and other cytokines and macrophage activation and infiltration. We also hypothesize that part of the anti-fibrotic effect of ACEi on target organ damage is mediated by Ac-SDKP interacting synergistically with kinins and NO. To test this hypothesis, we propose to conduct in vivo studies, using a combination of physiological, pharmacological and molecular approaches (gene deletion). In the first two aims we will determine the mechanisms by which Ac-SDKP prevents and reverses cardiac fibrosis. In Aim 1 we will study its effect on fibroblast proliferation and collagen synthesis and degradation. In Aim 2 we will study whether Ac-SDKP inhibits cardiac fibrosis in part by acting as an anti-inflammatory cytokine, decreasing proinflammatory cytokines and macrophage activation and infiltration and reactive oxygen species production. In Aim 3, we will study whether in hypertension Ac- SDKP improves diastolic dysfunction by reversing cardiac fibrosis. In Aim 4 we will determine whether endogenous Ac-SDKP antagonizes the inflammatory and fibrotic effect of angiotensin II (Ang II), aldosterone, and myocardial infarction (MI). In addition, we will study whether part of the cardiovascular protective effect of ACEi is due to an increase in AcSDKP, which interacts with kinins and NO to decrease extracellular matrix deposition in the cardiovascular system. These studies are significant since they will demonstrate: 1) the mechanism by which Ac-SDKP decreases cardiac fibrosis; 2) whether it has a therapeutic effect, improving diastolic and systolic dysfunction by reversing cardiac fibrosis; 3) whether it has a physiological role by antagonizing pro-fibrotic stimuli in the cardiovascular system; and 4) whether it mediates the cardiovascular protective effect of ACEi. In the future, non-peptidic analogues of Ac-SDKP could be developed to treat fibrosis in hypertension, aging, heart failure (HF) post-MI, diabetes and other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACTH INDUCTION OF CYTOCHROME P450 IN ADRENAL CELLS Principal Investigator & Institution: Waterman, Michael R.; Professor and Chairman; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 18-JUL-1992; Project End 31-MAR-2004
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Aldosterone
Summary: The chronic action of ACTH maintains optimal steroidogenic capacity in the adrenal cortex, assuring production of adrenal steroid hormones (cortisol, corticosterone and aldosterone) on demand. This process is mediated by cAMP exerting transcriptional pressure on genes encoding adrenocortical steroid hydroxylases (P450s) and related proteins. This competitive renewal proposes to determine how four homeodomain proteins binding to the predominant cAMP response sequence (CRS1) of bovine CYP17 (P450c17) interact with one another and the basal transcription machinery. Using in vitro transcription/translation, EMSA, cell transfection, in vitro transcription and mutagenesis; dimerization and transactivation domains in these homeodomain proteins will be identified along with coactivators and/or TAFs with which they interact. Adrenodoxin supports activity of mitochondrial P450s in the adrenal cortex and most other tissues. The gene encoding this 2Fe-2S protein is also regulated transcriptionally by ACTH(cAMP) and the novel protein binding to this CRS will be characterized in the same manner as CYP17 CRS1 binding proteins. This will permit comparison of cAMPdependent transcriptional regulation of a gene predominantly expressed in steroidogenic cells (CYP17) with one expressed in both steroidogenic and nonsteroidogenic cells. The signalling pathway required for exertion of transcriptional pressure by ACTH of steroidogenic genes is cAMP- responsive and inhibited by cycloheximide (CHX). The cAMP-responsive/ CHX-sensitive locus will be identified as a means of understanding this signalling pathway. The proposed studies will establish for the first time at the biochemical level how peptide hormones from the anterior pituitary control levels of steroidogenic enzymes as well as providing detailed insight into the signalling pathway required for this process. These events are required for the biosynthesis of steroid hormones leading to reproductive capacity and metabolic homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALDOSTERONE IN ANGIOTENSIN II-INDUCED HYPERTENSION Principal Investigator & Institution: Ortiz, Rudy M.; Physiology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): The renin-angiotensin-aldosterone system (RAAS) regulates Na+ balance and blood pressure. Angiotensin II (Ang II) infusion induces hypertension and increases aldosterone (aldo), which should increase Na+ and water retention and exacerbate the hypertension. Elevated aldo has also been associated with fibrosis and tissue damage. Therefore, blockade of RAAS components should attenuate Ang II-induced hypertension. However, the contribution of aldo in renal Na+ and water handling during Ang II hypertension remains inconclusive. This study will test the hypothesis that aldo receptor blockade decreases Na+ and water retention and attenuates blood pressure in Ang II-induced hypertension. Specifically, the aims are 1) to determine the contribution of aldo to Na+ and water retention in Ang II-induced hypertensive rats treated with placebo or mineralocorticoid antagonists maintained, and 2) to determine the contribution of aldo to Na+ and water retention during Ang IIinduced hypertension independent of elevated blood pressure and in the presence of reduced renal perfusion pressure. Unlike previous studies, the present study will provide a more comprehensive examination of the renal effects induced by aldo antagonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALDOSTERONE DYSFUNCTION
IN
VASCULAR
REMODELING
11
AND
Principal Investigator & Institution: Ramachandran, Vasan S.; Associate Professor of Medicine; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2004; Project Start 01-APR-2000; Project End 31-DEC-2008 Summary: (provided by applicant): This is a competing continuation of a K 24 award from the candidate who is an Associate Professor of Medicine at Boston University School of Medicine (BUSM), and a senior clinical investigator at the Framingham Heart Study (FHS). His training in cardiology and epidemiology, mentoring and program development skills, and excellent track record in conducting and mentoring clinical research render him a suitable candidate for this research career award. During the award period, the candidate will continue to spend 40% effort on the research outlined below (including mentoring), 45% effort on his other research support, and 15% on clinical work. His long-term career objectives are to work as a clinical investigator building on the research theme of investigating biomarkers of preclinical heart failure, genetic and environmental correlates of ventricular remodeling, epidemiology of vascular dysfunction (endothelial dysfunction and conduit artery stiffness) and abnormal ventriculo-vascular coupling (and relations to heart failure risk), and to mentor young clinical investigators. The interdisciplinary research group, the highquality research infrastructure, the opportunities for mentoring, and the support of senior colleagues render the FHS and BUSM ideal settings for the candidate's pursuit of his career as a clinical investigator. The current proposal investigates the role of aldosterone in mediating vascular dysfunction and has the following specific aims: 1. To assess the clinical, inflammatory and genetic correlates of serum aldosterone. 2. To perform cross-sectional analyses on the relations of serum aldosterone to carotid intimal medial thickness, and to dynamic measures of central conduit artery function. 3. To perform cross-sectional analyses on the relations of serum aldosterone to select measures of brachial arterial endothelial function; and to microalbuminuria. 4. To describe the relations of serum aldosterone prospectively to incident CVD events The proposed K 24 award will allow the candidate and his mentees to focus on the vascular biology of aldosterone and its relations to vascular dysfunction and risk over the next five years, and will provide the candidate an opportunity for nurturing the next generation of patient-oriented researchers. The mentorship plan consists of mentoring the research of and teaching a module on clinical research design to fellows at the FHS and BUSM and will contribute directly to the growth and development of young clinical investigators at these institutions. Activities for career development of the candidate are also planned in the areas of proteomics and genetic epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALDOSTERONE, HYPERTENSION AND THE BRAIN Principal Investigator & Institution: Gomez-Sanchez, Elise P.; Professor and Research Scientist; Medicine; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 01-JUL-1981; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Aldosterone is a powerful mineralocorticoid, which plays a significant role in the pathogenesis of several forms of human and experimental hypertension. In excess it is also responsible for direct deleterious effects on the heart, and cerebral and renal vasculature, independent of its
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Aldosterone
effect on the blood pressure. The applicant has demonstrated that Aldosterone biosynthesis occurs in vascular tissues and the brain, in addition to the adrenal zona glomerulosa. The amount of aldosterone synthesis in the brain is very small, but it may have paracrine effects through receptors located within a short distance of its site of synthesis. They have published evidence supporting the action of central mineralocorticoids in the hypertension of the Dahl Salt-Sensitive rat. The concentration of aldosterone in the brain is higher than that in plasma, even in normal outbred rats. A significant proportion, approximately 2/3, occurs as low polarity acyl esters of aldosterone. Acyl esters of several steroids are reported to accumulate in the CNS. They found the presence of two different aldosterone acyl esters, an oleate, and what may be one of the three possible aldosterone monoactates isomers. Preliminary evidence suggests that acylation of aldosterone increases its biological activity in vivo. They propose the hypothesis that: Aldosterone action in brain is potentiated or prolonged by acylation. The specific aims to test this hypothesis are 1) Isolation and elucidation of the structures of acyl esters of aldosterone found in the brain. 2) Measurement of aldosterone acyl esters in the serum and specific areas of the brain in normal and pathophysiologic conditions. 3) Assessment of the hypertensinogenic activities of the aldosterone acyl esters. 4) Study of the metabolism of aldosterone and corticosterone and the regulation of the synthesis of low polarity derivatives in the brain, including the identification of the sites of formation of aldosterone acyl esters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOTENSIN II, OXIDATIVE STRESS, AND ATHEROSCLEROSIS Principal Investigator & Institution: Cohen, Richard A.; Associate Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's Abstract): Oxidative stress is thought to participate in vascular dysfunction and remodeling that accompanies angiotensin II (AII)-induced hypertension, but the source and cellular sources of oxidant species and their precise role is poorly understood. Recent studies in the laboratories of the two PI's have elucidated a novel role for the aortic adventitia as the site of elaboration of both superoxide anion (O2-) and nitric oxide (NO) radicals, indicating that the adventitia is a major site of oxidative stress. New studies indicate that the increased elaboration of O2by AII is indicated by prominent nitrotyrosine staining of the adventitia, likely as a result of production of the reaction product of O2- and NO, peroxynitrite (OONO-). There are many sources of O2- in the vascular wall, but recent studies indicate that multiple subunits of the neutrophil NAD(P)H oxidase are present in the adventitia where O2- is greatest. Preliminary studies in which AII was infused into mice that are deficient in one NADPH oxidase subunit, gp91phox, show a blunted aortic O2-, hypertrophic, and proliferative response to AII compared with wild type mice, despite a similar hypertensive response. Proposed studies in rats and mice will elucidate the hypothesis that oxidative stress mediated by adventitial NAD(P)H oxidase-derived O2participates in the myogenic, hypertrophic, and proliferative vascular response in AIIinduced hypertension. The proposed studies will also take advantage of preliminary work on Apo E deficient mice (EKO) to determine the significance of AII-induced oxidative stress in atherosclerosis. Preliminary studies in these mice indicate that captopril and losartan reduce atherosclerosis (suggesting a role for AII), and that hypothetically under the influence of AII, there is increased production of O2- and OONO-, as indicated in preliminary studies by nitrotyrosine. Studies in Apo E deficient mice that overexpress human Cu/Zu SOD and double knockouts deficient in Apo E and
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gp91 phox or the AII type receptor, will help to elucidate the hypothesis that AIIinduced oxidative stress contributes significantly to vascular dysfunction and remodeling in atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOTENSIN-(1-7) AND REGULATION OF VASCULAR GROWTH Principal Investigator & Institution: Tallant, Elisabeth Ann.; Associate Professor; Wake Forest University 1834 Wake Forest Road Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Vascular smooth muscle cell (VSMC) growth is regulated by a balance between proliferative and anti-proliferative factors. Angiotensin-(1-7) [Ang-(1-7)] inhibits VSMC growth and reduces neointimal formation following vascular injury. The reduction in vascular growth in response to treatment of VSMC with Ang-(1-7) was prevented by the sarcosine antagonists of Angiotensin II (Ang II) but not by AT1 or AT2 receptor antagonists. This suggests that the anti-proliferative effects of Ang- (1-7) are mediated by a novel non-AT1, non-AT2 receptor, the AT(1-7) receptor. We hypothesize that Ang-(1-7) inhibits vascular growth by the production of prostacyclin, an increased in cAMP production and the activation of cAMP-mediated cellular responses. Further, the anti- proliferative effects of Ang-(1-7) are mediated by the AT(1-7) receptor. Thus, the goals of this project of this project are to determine the mechanisms by which Ang(1-7) inhibits VSMC growth and define the receptor mediating the effects of Ang-(1-7) in the vasculature. In Specific Aim 1, the contribution of prostacyclin to the regulation of VSMC growth by Ang-(1-7) in the vasculature. In Specific Aim 1, the contribution of prostacyclin to the regulation of VSMC growth by Ang-(1- 7) will be examined and the role of distinct metabolites of arachidonic acid in the counter-regulatory effects of Ang II and Ang-(1-7) on vascular growth will be evaluated. In Specific Aim 2, the participation of cAMP and cAMP-mediated responses in vascular growth inhibition by Ang-(1-7) will be determined. In Specific Aim 3, the receptor activated by Ang-(1-7) in VSMC will be pharmacologically characterized and its cDNA will be identified by expression cloning. RT-PCR analyses will be used to determine whether the AT(1-7) receptor is altered in vascular tissues from hypertensive rats (both spontaneous hypertensive rats or (mRen2)27 transgenic rats) or in rats fed a low salt diet, in parallel to studies described in Projects 1, 2 and 3. The results of these studies will identify the receptor and the signaling pathway(s) activated by Ang-(1-7) to counter-regulate the proliferative effects of Ang II and evaluate the contribution of the AT(1-7) receptor to the regulation of arterial pressure in hypertensive animals and during activation of the renin-angiotensin system by low salt. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANGIOTENSIN, HYPERTENSION
SODIUM
AND
GENES
IN
PRIMATE
Principal Investigator & Institution: Haywood, Joseph R.; Professor; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Sodium-dependent hypertension has long been associated with a defect in renal function. Experimental models as well as human studies have also suggested that an alteration in genetic expression may contribute to the hypertensive process. Sodium-lithium countertransport (SLC) activity is one mechanism that helps maintain intracellular sodium concentrations, and in some
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Aldosterone
hypertensive patients, SLC activity is increased. These individuals also experience an inappropriate response to sodium challenges that appears to result from a lack of suppression of the renin-angiotensin-aldosterone system (RAAS). The association between SLC activity and hypertension is genetically determined since it occurs in families. It is uncertain whether this reflects an alteration in the gene for SLC, one of the genes that may increase RAAS function, or an interaction between genes for the two systems. The goal of the proposed studies is to examine the relationship between SLC activity and the RAAS in a non-human primate model in which the SLC phenotype is high or low. The hypothesis to be tested is that a high SLC activity is associated with inappropriately high RAAS function and a greater arterial pressure sensitivity to dietary sodium. In three aims, the contributions of peripheral and central RAAS components to sodium-dependent hypertension will be studied in baboons with the high and low SLC phenotypes. In the first aim, regulation of the RAAS will be examined in high and low SLC animals during a step-wise increase in sodium intake. These experiments will determine whether animals with high SLC activity have a reduced ability to suppress the RAAS and develop salt-sensitive hypertension. The second aim will investigate the role of angiotensin and aldosterone in the stimulation of hypertension by sodium and their ability to cause blood pressure to rise in high and low SLC animals. This aim will determine whether by raising plasma angiotensin or aldosterone the high SLC animals are more likely to become hypertensive. The third aim will focus on central nervous system mechanisms associated with an inappropriately high RAAS in high and low SLC animals. These studies will determine whether the high SLC activity results in more sensitive central mechanisms driving the sympathetic nervous system to raise arterial pressure. These studies will help provide data to determine whether an inappropriately high RAAS activity can cause hypertension. Importantly, this work will also reveal whether the genetically determined phenotype of high SLC is important in predisposing an animal to sodium-dependent hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOTENSIN: A LINK BETWEEN OBESITY AND HYPERTENSION Principal Investigator & Institution: Cassis, Lisa A.; Professor; Pharmaceutical Sciences; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 03-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The proposed studies are in response to RFA-HL-02016 and will address the working hypothesis that a moderately high fat diet (MHF) stimulates the adipose renin-angiotensin system, contributing to obesity-related elevations in blood pressure. Preliminary data demonstrates that rats fed a MHF diet segregate into obesity prone (OP) versus obesity-resistant (OR) populations. In OP rats, blood pressure was increased coincident with activation of the systemic and adipose renin-angiotensin system. The first hypothesis is that a MHF diet activates the adipose renin-angiotensin system, resulting in an increase in circulating angiotensin peptides and blood pressure. Time-dependent regulation of adipose versus non-adipose components of the renin-angiotensin system will be examined in control, OR and OP rats and compared to the time course for elevations in blood pressure. The contribution of various circulating angiotensin peptides to blood pressure elevations in control, OR and OP rats will be determined. The second hypothesis is that adipocytes from OP rats exhibit a redistribution of free cholesterol from the plasma membrane to intracellular triglyceride pools, thereby increasing the activity of sterol regulatory binding protein-2 and stimulating angiotensinogen (Ao) mRNA expression. This would provide an adipocyte-specific mechanism for regulation of Ao gene expression in response to the
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MHF diet. The intracellular localization of free cholesterol in adipocytes prepared from control, OR and OP rats will be determined and compared to the level of Ao mRNA expression. The effect of depletion of intracellular free cholesterol pools on adipocyte Ao mRNA expression will be determined. The third hypothesis is that elevations in circulating angiotensin peptides increase blood pressure in OP rats by stimulating sympathetic drive. The responsiveness of the baroreceptor reflex and the blood pressure response to ganglionic blockade will be determined in control, OR and OP rats. A second approach will determine the effect of neonatal sympathectomy on blood pressure elevations in diet-induced obesity. In hypothesis 4 a novel animal model will be developed to determine the effect of targeted deficiency of Ao in adipose tissue on blood pressure regulation in diet-induced obesity. The goals of this research are to definitively determine the role of adipose-derived angiotensins and the systemic reninangiotensin system in blood pressure elevations in diet-induced obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOTENSINS, KININS AND AT2 RECEPTORS IN TARGET ORGAN DAMAGE Principal Investigator & Institution: Yang, Xiao-Ping; Henry Ford Health System 2799 W Grand Blvd Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant) Hypertension is a major risk factor for development of cardiovascular disease. Activation of the renin-angiotensin-aldosterone system (RAAS) plays an important role in this pathological process, since blocking the RAAS with ACEi or AT1-ant significantly improves cardiac function, regresses LV remodeling and prolongs survival in patients with cardiovascular disease. Besides RAAS inhibition, kinins and NO have been shown to participate in the cardioprotective effects of ACEi. During AT1 inhibition, activation of the AT2 receptor may also lead to the release of NO, either directly or via kinins. Here we propose to test the general hypothesis that Ang II acts locally in the heart via the AT1 receptor independently of its systemic effect, resulting in cardiac remodeling and dysfunction. We also hypothesize that in the heart Ang II acts either directly or via release of endothelin (ET), reactive oxygen species (ROS) and nuclear factor-kappa beta (NF-kappa beta), promoting inflammation, and these effects are mediated via the AT1 receptor. Kinins, NO and activation of the AT2 receptor antagonize the cardiac effects of Ang II. We propose to use a combination of molecular, physiological, and pharmacological approaches and several lines of bioengineered mice to test these hypotheses. In Aim 1, we will use transgenic mice overexpressing Ang II in the heart to study whether 1) increased Ang II in the heart causes cardiac remodeling and dysfunction without increasing BP, and these local effects are mediated by release of ET, ROS and NF-kappa beta, in turn stimulating proinflammatory processes; and 2) in the presence of a hemodynamic load, Ang II in the heart accelerates cardiac remodeling and dysfunction. In Aim 2, we will use transgenic mice overexpressing the AT2 receptor in the heart and AT2 receptor knockout mice to test the hypothesis that AT2 receptors expressed in the heart have a cardioprotective effect which is partially mediated by release of kinins and NO. We will further study whether activation of AT2 receptors increases kinins via stimulation of kininogenases other than tissue kallikrein. In Aim 3, using bradykinin B2 receptor knockout mice (B2 /-), we will test the hypothesis that expression of the B1 receptor is increased in the heart and vascular tissue in hypertension and myocardial infarction (MI), which may have an important vasodepressor and anti-trophic role. Dual blockade of B1 and B2 receptors may accelerate development of hypertension and LV hypertrophy and worsen
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Aldosterone
cardiac remodeling and dysfunction in mice with MI. In Aim 4, using eNOS -/-, nNOS /- and iNOS -/- as well as double knockout (e/nNOS -/-) mice, we will test the hypothesis that NO released from eNOS and nNOS has a cardioprotective effect, while NO released from iNOS (which produces high amounts of NO) has a detrimental effect on the heart, especially when ROS formation is increased. These studies are significant, since they will demonstrate whether or not Ang II has a direct effect in the heart and whether these effects are antagonized by activation of the AT2 receptor, kinins and NO. These studies could lead to better treatment of target organ damage in hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANIMAL HYPERTENSION
MODELS
FOR
STUDYING
THE
GENETICS
OF
Principal Investigator & Institution: Smithies, Oliver; Excellence Professor of Pathology; Pathology and Lab Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-AUG-2007 Summary: (provided by applicant): The long term objective of the research proposed in this continuation remains to help unravel the genetic complexities of essential hypertension. For the coming grant period, we have chosen three aims:Specific aim (i) will complete or extend our quantitative analyses to include titrations of the genes coding for: renin (Ren-1), aldosterone synthase (Cyp11b2), adrenomedullin (Adm) and its receptor (Ca/cr1). the calcitonin receptor like receptor. Blood pressures will be determined and quantitative RT-PCR will be used to assess the degree to which homeostatic compensations have been induced. The effects of environmental changes, such as dietary salt and pregnancy, will be investigated. Our expectation is that these analyses will identify additional genes predicted to cause changes in blood pressure or its homeostasis if their expression varies as a result of genetic polymorphisms in humans.Specific aim (ii) will explore a new problem--how blood pressure and its homeostasis are affected by combining high expressing and low expressing genetic variants within the same physiologic system (for example Agt & Agtr1a) and in different systems (for example Agt & Npr1). We will breed currently available animals to give four combinations (high & high, high & low, low & high and low & low) for each pair of genes. We will develop computer simulations that include interactions between different systems, and will compare them with experimental data. Any inadequacies revealed will facilitate improvement of the models. This to-and-fro process is expected to greatly increase current understanding of why some combinations of genetic variations are detrimental and others beneficial.Specific aim (iii) will investigate the mechanisms underlying highly significant gender-related differences that we have found occur (a) in the expression and responses of more than 10 genes related to the control of blood pressure; (b) in the relationship between blood pressure and variations in the liver expression of Agt that are unrelated to gene copy number, and (c) between kidney expression of Agtr1a and Kiki, the gene coding for kallikrein. All three of these gender effects have direct relevance to humans, and we expect that their analysis will reveal some previously unknown causes underlying the differences in cardiovascular risk factors in males and pre-menopausal females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AT1 RECEPTOR CONTROL IN CHRONIC HYPERTENSION ATTENUATION Principal Investigator & Institution: Raizada, Mohan K.; Professor; Physiology and Functional Genomics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from Applicant's Abstract): Hypertension is a complex pathological state that is manifested as chronic blood pressure. It affects all vital organs, and is a major risk for many cardiovascular diseases. Overwhelming evidence has established that an altered renin-angiotensin system (RAS) plays a key role in the development and establishment of hypertension. Thus, traditional pharmacological agents that influence the RAS are effective antihypertensive therapy. In spite of its success, the traditional therapy is not a cure of hypertension and suffers from many side effects and compliance issues. As a result, the investigators set out to investigate the possibility of genetic targeting of the RAS as a means to control hypertension on a long-term basis. Their studies have established that a single dose of a retroviral vector containing angiotensin II type I receptors antisense (AT1R-AS) or angiotensin-converting enzyme antisense (ACE-AS) prevents hypertension for life in the spontaneously hypertensive rat (SHR). These observations led them to conclude that the antisense therapy (AS) is conceptually sound, technically feasible, and may hold promise for cure of hypertension. The objective during this grant period is to test an overall hypothesis that AS targeting to regulate the expression of the RAS would prevent the development of hypertension on a permanent basis as a result of genomic integration of AT1R-AS or ACE-AS. If successful, a regulatable system of the AS, and thus antihypertensive actions, could be controlled on demand. The aims of the study are: 1) investigate the mechanism of a long-term protection against hypertension by the AT1R-AS gene therapy; 2) investigate involvement of central angiotensin in antihypertensive actions of AT1R-AS gene therapy; 3) investigate the role of tissue RAS in hypertension, and 4) establish long-term reversal of hypertension by the use of a novel viral vector system. State-of-the-art techniques of gene transfer, viral vectors, and molecular biology will be used to accomplish these aims. The investigators believe that this research proposal is low risk in nature and will have high impact in the development of strategies for long-term control of hypertension. The outcome of this research has a potential to be immediately adapted for the treatment of human hypertension and other cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BLOOD PRESSURE IN POSTMENOPAUSAL WOMEN: A GCRC STUDY Principal Investigator & Institution: Seely, Ellen W.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This is a Mid-Career Investigator (K 24) proposal for Ellen Seely, MD. The goal of this proposal is threefold. First, it would increase the depth of Dr. Seely's research by enabling the investigator to receive further advanced training in human genetics. Second, it would give the investigator the supported time to formally train young investigators in patient-oriented research in the field of hormonal control of blood pressure. Third, it would allow the investigator to use her experience as Associate Program Director of the General Clinical Research Center (GCRC) to teach the next generation of patient-oriented researchers about the use of a GCRC for the study of human pathophysiology using varied GCRC-based investigative techniques. Dr. Seely's
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Aldosterone
research topic "Blood Pressure in Postmenopausal Women: a GCRC Study" serves as fertile ground for a K24. Hypertension affects over 20 million women in the United States and the majority of these women are postmenopausal. Although there is clearly a genetic component to hypertension in both men and women, its incidence increases dramatically in women following menopause superceding that in men and suggests that the hormonal milieu of the premenopausal state may be protective against the manifestation of hypertension. The overall goal of Dr. Seely's research plan is to utilize the GCRC for detailed studies of the pathophysiology of hypertension in postmenopausal women. Dr. Seely plans to determine how polymorphisms of genes of the renin-angiotensin-aldosterone system (RAAS), a major regulator of blood pressure, are influenced by estradiol. An understanding of the interaction of estradiol with specific polymorphisms of the RAAS that lead to blood pressure lowering may enable the development of selective estrogen receptor modulators that have antihypertensive effects. Thus, funding of this proposal will allow Dr. Seely to expand her own research career and simultaneously provide time to expand her mentorship role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR MECHANISMS OF MINERALCORTICOID ACTION Principal Investigator & Institution: Johnson, John P.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-MAY-1995; Project End 31-DEC-2007 Summary: (provided by applicant): Maintenance of extracellular fluid volume homeostasis is essential for hemodynamic stability, and abnormalities of renal sodium handling have been linked to cardiovascular disease and hypertension. Ultimate regulation of sodium excretion occurs in the distal nephron via conductive transport through amiloride sensitive epithelial Na+ channel (ENaC). ENaC expression and activity in the apical membrane of epithelial cells is the rate limiting step in Na+ reabsorption not only in the kidney collecting duct, but in airway epithelia and colon as well. Aldosterone is a major regulator of ENaC expression and activity in responsive epithelia. Studies are designed to examine the mechanism of aldosterone regulation of ENaC. Work in the previous grant period has established that aldosterone stimulates the post-translational methylation of betaENaC which alters channel gating. Studies are now proposed to examine the site and mechanism of this regulation and potentially define a gating site in ENaC. We have demonstrated that EnaC appears to be localized, in part at least, to specialized areas of membrane called lipid rafts and this localization is regulated by aldosterone. Raft association of ENaC is a new finding and could be important for ENaC trafficking, apical membrane expression and association with regulatory proteins. We will examine the mechanism by which lipid raft association affects ENaC function and aldosterone regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CENTRAL ANGIOTENSIN IN FLUID BALANCE & HYPERTENSION Principal Investigator & Institution: Phillips, M. Ian.; Vice President for Research; Physiology and Functional Genomics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-JUL-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL PHARMACOLOGY OF LOOP DIURETICS Principal Investigator & Institution: Brater, D Craig.; Chairman and Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 31-AUG-2005 Summary: (adapted from Investigator's abstract) During the past grant period, the investigators performed a variety of studies asking clinically pertinent questions about more effective uses of diuretics. In the current proposal, they propose two large new studies that logically extend their previous work. The aim of the first study is to delineate the mechanism of the pharmacodynamic resistance to loop diuretics that occurs in patients with congestive heart failure (CHF). This resistance could occur by increased proximal tubular reabsorption of sodium, increased distal reabsorption of sodium and/or a change in the dynamics of the interaction of the loop diuretic with the Na-K-2Chl transporter of the loop of Henle. The answers to these questions should illuminate the mechanisms of sodium retention in CHF and thus allow more rational and effective use of diuretic combinations. This study will entail using diuretics with sites of action at different portions of the nephron as probes of this pathophysiology. They will employ methods familiar to them in clinical studies designed to systematically examine the role of different nephron sites in causing diuretic resistance. They will also perform a clinic-based study in which they will attempt to define causes for clinical deterioration in patients with CHF. This study will utilize a unique electronic medical record at the University of Indiana, the Regenstreif Medical Record System (RMRS). This system captures a wealth of clinical data that will be extracted and linked with compliance data, plasma renin and aldosterone activity and quality of life assessments obtained during this study to answer a series of focused questions. Each patient studied will be followed for at least one year. The investigators will perform multivariate analyses to determine causes of clinical deterioration. These data will provide insights into the causes and pathophysiology of decompensation in patients with CHF, thus enhancing our understanding of this increasingly prevalent disease and leading to better therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL TRIAL TO SLOW THE PROGRESSION OF ADPKD Principal Investigator & Institution: Schrier, Robert W.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) affects one in 500-1000 Americans and leads to end-stage renal disease (ESRD) in 50% of patients by age 60 years. Moreover, the life expectancy of ADPKD patients is significantly reduced compared with the general population, despite the availability of dialysis and transplantation, due to premature cardiovascular mortality. Recent advances have lead to greater understanding of the mechanisms of ADPKD, and several agents have been found to slow cyst growth in animal models. However, clinical interventions to ameliorate the course of ADPKD in humans are lacking. Therefore, the National Institute of Diabetes and Digestive and Kidney Diseases has proposed a PKD Clinical Trials Network to design and implement clinical trials to slow the progressive loss of renal function in PKD, including a large trial on blockade of the reninangiotensin-aldosterone system (RAAS). The PKD Research Center at the University of
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Aldosterone
Colorado Health Sciences Center maintains a database of nearly 800 families with ADPKD, and over 1000 family members have participated in previous clinical studies at our Center. Additional patients with ADPKD are available for recruitment from the Polycystic Kidney Research Foundation and from agreements with local health care providers. Thus, we are confident we can identify 500 patients with ADPKD who are eager and eligible to participate in a clinical trial. We propose both a large randomized controlled clinical trial featuring blockade of the RAAS and a pilot study to determine if treatment with an antiangiogenic agent slows the rate of renal growth in patients with ADPKD. Working in collaboration with the PKD Clinical Trials Network, our goal is to identify interventions that not only slow but prevent progression of ADPKD to ESRD, and interventions that ameliorate the cardiovascular complications in ADPKD. A 2 X 2 factorial design is proposed to examine the hypothesis that RAAS inhibition and rigorous blood pressure control will slow progression in advanced ADPKD and prevent progression of renal and cardiovascular disease in early ADPKD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL UNWEIGHTED RAT
OF
SODIUM
INTAKE
IN
THE
HINDLIMB
Principal Investigator & Institution: Cunningham, J T.; Dalton Research Center; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Verbatim from the application): In the hind limb unweighted (HU) rat model of bed rest and microgravity, HU results in a central movement of body fluid, diuresis and natriuresis, resulting in a decrease in plasma volume. We have observed that rats increase ingestion of saline solution during 24h HU. Further, this ingestion of saline inhibits the decrease in plasma volume normally observed in 24h HU rats. The studies proposed examine the integration of neural and humoral factors influencing sodium ingestion in the HU model of bed rest. The specific aims of the study are: Specific aim 1: Investigate the role of the renal nerves in promoting sodium intake during 24 h HU. Specific aim 2: Investigate the role of hormones in promoting sodium intake during HU. Specific aim 3: Examine the role of the cardiac afferent nerves in regulating the intake of sodium. Specific aim 4: Compare short term (24 h) and long term (14 d) effects of HU on sodium ingestion and plasma volume. We hypothesize that increases in renal afferent nerve activity is critical to HU-induced sodium ingestion. Furthermore, elevated aldosterone may contribute to the ingestion of sodium while stimulation of cardiac afferent nerves may inhibit sodium intake in this model. Integration of these signals by the central nervous system results in a modest sodium intake and maintains plasma volume during HU. During prolonged HU, adaptations may occur which further influence both the ingestion of sodium and blood volume. Understanding bed rest and microgravity-induced changes in body fluid balance requires understanding such factors as the acquisition of solutes. It is hoped that these experiments will contribute to an understanding of both the regulation of body fluid during prolonged bed rest and the problems associated with return to normal posture. Additionally, these data may contribute to understanding of health problems associated with an aging population and with cardiovascular disease such as congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROLLED TRIAL OF RENIN ANGIOTENSIN BLOCKADE IN ADPKD Principal Investigator & Institution: Torres, Vicente E.; Chairman; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): The overall hypothesis of the proposed studies is that an intensified interventional strategy aimed at blocking the renin angiotensin system at multiple levels (angiotensin II-receptor interaction by an angiotensin II AT1receptor blocker or ARB, angiotensin II generation by an angiotensin I convertingenzyme inhibitor or ACEI, an angiotensin II AT1-receptor density and intracellular signaling by inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase or statin) will slow down the progression of the renal cystic disease in patients with normal or near-normal renal function (GFR > 60ml/min/1.73m2) and the decline of renal function in patients with mild to moderate renal insufficiency (30-60 ml/min/1.73 m2) (Main Study) and that the success of this strategy will be predicted by the extent to which it corrects the intrarenal hemodynamic alterations associated with autosomal dominant polycystic kidney disease (ADPKD) (Pilot Study). The primary end-points for the Main Study will be a 15% increase in kidney volume or a 30% increase in cyst volume measured by MR in patients with normal or near-normal renal function and a 50% reduction in GFR or a doubling in serum creatinine in patients with mild to moderate renal insufficiency. MR determinations of renal blood flow (RBF), renal vascular resistance (RVR) and arterial compliance will be obtained to ascertain the extent to which the hemodynamic changes in response to therapeutic interventions can predict their success in delaying the progression of the renal cystic disease or the decline of renal function. Similar methodology will be used to ascertain the potential value of novel antihypertensive therapies in ADPKD. The protocols for the Main Study will be conducted in 500 patients, 250 recruited at the Mayo Clinic, 150 recruited at KUMC, and 100 at the Cleveland Clinic. Approximately one-half of these patients will have normal or near-normal renal function and one-half have mild to moderate renal insufficiency. The protocols for the Pilot Study will be conducted only at the Mayo Clinic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOKINE MODULATION OF THE CARDIAC FIBROBLAST PHENOTYPE Principal Investigator & Institution: Long, Carlin S.; Associate Research Scientist; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 22-DEC-1997; Project End 31-JUL-2006 Summary: (provided by applicant): During heart failure, cardiac fibroblasts undergo pathphysiologic changes in cellular phenotype which recapitulate the processes of injury, inflammation, and wound healing. In the failing heart, these responses culminate in cardiac fibrosis, which contributes importantly to the deterioration of myocardial performance. These phenotypic changes include altered proliferation, migration, extracellular matrix synthesis, and production of autocrine-paracrine mediators. Alterations of cardiac fibroblast phenotype are likely driven by humoral substances acting on cell surface receptors to regulate intracellular signaling cascades, leading to activation of defined transcription factors. However, understanding of fibroblast biological responses in terms of coordinated programs of gene transcription is currently limited. The overall hypothesis of this work is that the phenotype of the activated
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cardiac fibroblast is determined by the combinatorial actions of several key proinflammatory cytokines and fibrogenic growth factors. We propose further that this phenotype represents a fundamental change in the transcriptional program of the cell, resulting from interactions of the signaling cascade(s) and downstream nuclear regulators initiated by these agonists. To elucidate the signaling mechanisms which underlie these phenotypic endpoints, the following specific aims are identified: Specific Aim 1 will determine the signaling mechanisms of cytokine and growth factor regulation of fibroblast proliferation; Specific Aim 2 will investigate cytokine and growth factor regulation of fibroblast migration and cytoskeletal organization; Specific Aim 3 will determine signaling mechanisms of cytokine and growth factor regulation of extracellular matrix metabolism; and Specific Aim 4 will define cytokine regulation of autocrine-paracrine mediators of fibrosis; namely, the Renin-Angiotensin and TGFbeta systems. Our experimental system utilizes cultures of cardiac non-myocytes (fibroblasts) from neonatal and adult rats. Investigations will focus on the pro-inflammatory cytokines IL-1, TNFalpha, IL-6, and IFNgamma; and the fibrogenic growth factors Angiotensin II, Aldosterone, and TGFb. Activation of prototypic signaling cascades and their downstream transcription factors, including MAP Kinase-AP-1, NF-kappaB, and JAK-STAT, will be determined. Signaling pathways will be manipulated experimentally using pharmacological inhibitors, and by expression of recombinant signaling molecules using adenovirus vectors. Insights into convergent mechanisms regulating fibroblast phenotype will offer novel strategies for therapeutic management of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DATA COORDINATING CENTER FOR PKD TREATMENT NETWORK Principal Investigator & Institution: Miller, J. Philip.; Professor; Biostatistics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): Washington University proposes to establish the Data Coordinating Center (DCC) for the Polycystic Kidney Disease Treatment Network (PKD-TN) within the Division of Biostatistics. WU performs a similar function for the NIDDK-sponsored CRISP study that is developing imaging parameters to follow the progression of Polycystic Kidney Disease (PKD). WU generally, and this investigative team specifically, has a strong record of experience as the DCC for multicenter studies. The DCC will participate as a key member of the Steering Committee, taking a leadership role in planning the studies, leading the statistical analyses and reporting of these studies. A web-based data entry system, based on the one currently being used for CRISP, will be customized for the needs of the PKD-TN. The DCC will serve as the communications hub for the PKD-TN, arranging meetings, telephone and electronic communications and producing and archiving study-related documents. A three-group, double-masked, randomized, multicenter, placebo-controlled trial will address whether either an ACE inhibitor or an angiotensenin 2 antangonist will retard the progression of renal impairment in PKD. The trial will enroll 1,800 PKD subjects with a wide range of renal function and follow them for 3-5 years. The primary endpoint will be that of time to death, ESRD or a doubling of the serum creatinine level. GFR levels will be assessed annually with a central laboratory and will be used as a secondary endpoint. The GFR measurements will allow us to address questions about variations in treatment effect according to the severity of renal impairment and the presence of common features of the disease such as hypertension and proteinuria. Blood and urine samples will be collected at baseline and annually and stored in the NIDDK's repository for future
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pharmocogenitic studies and future studies of biomarkers of the progression of PKD. An early Phase II trial of BMP-7, a cytokine which has an essential role in coordinating the formation of the emerging metanephos, is proposed. BMP-7 has been shown to maintain renal function in animal models with acute and chronic renal disease and to reduce renal hypertrophy. A simple, two-group, placebo controlled, randomized clinical trial will be conducted to determine whether BMP-7 can retard the growth rate of the kidneys in PKD subjects. MRI-based imaging will be used to measure kidney size for the trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENAC REGULATION BY NEDD4-2 AND SGK Principal Investigator & Institution: Snyder, Peter M.; Associate Professor of Medicine; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2006 Summary: (provided by applicant): The epithelial Na+ channel, ENaC, forms the pathway for Na+ absorption in the kidney collecting duct and other epithelia (1, 2). Specific ENaC mutations lead to excessive channel expression at the cell surface, resulting in a genetic form of hypertension (Liddle's syndrome). Aldosterone and other steroid hormones regulate Na+ absorption by altering the expression of ENaC at the cell surface. Thus, understanding the mechanisms that control ENaC surface expression wifi provide critical new insights into the molecular mechanisms of Na+ homeostasis, and the pathogenesis of hypertension. Previous work found that Nedd4 and Nedd4-2 reduce ENaC surface expression by targeting the channel for degradation. A defect in this pathway is responsible for Liddle's syndrome. Conversely, serum and glucocorticoidregulated kinase (SGK), a down-stream mediator of aldosterone, increases ENaC surface expression. Our preliminary studies suggest the novel hypothesis that these two pathways are not independent, but that they converge in a common pathway to regulate Na+ absorption. The goal of this project is to test the hypothesis that SGK modulates ENaC surface expression in part through Nedd4-2 binding and phosphorylation, and to understand the mechanisms involved. In the first specific aim, we will test the hypothesis that SGK phosphorylates Nedd4-2. We will identify the specific residues that are phosphorylated, and will test whether phoshorylation alters Nedd4-2 function. In specific aim two, we will test the hypothesis that SGK binds to Nedd4-2. We will identify the sequences that mediate this interaction, and test the functional role of binding. Specific forms of hypertension are caused by defects in ENaC regulation by Nedd4 family members (Liddle's syndrome) and defects in mineralocorticoid and glucocorticoid signaling signalling (e.g. glucocorticoid-remediable aldosteronism). Thus, our work will provide a new understanding of these forms of hypertension. In addition, by elucidating the pathways and proteins responsible for blood pressure control, this work may provide important new insights into the molecular causes of essential hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPITHELIAL NA CHANNELS AND REGULATION OF NA EXCRETION Principal Investigator & Institution: Palmer, Lawrence G.; Professor; Physiology and Biophysics; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007
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Aldosterone
Summary: (provided by applicant): Epithelial Na channels are expressed in the distal parts of the mammalian nephron, and are known to be regulated by the reninangiotensin-aldosterone axis. The role of these channels and their regulation by mineralocorticoids in the daily regulation of sodium excretion by the kidneys will be explored. Preliminary data indicate that when rats are given a low sodium diet, they can adjust their renal Na excretion within 15 hours and that increased reabsorption through Na channels can account for a large fraction of the reduced excretion rates. We will assess the role of the channels with different degrees of Na depletion, measuring both channel activity and overall urinary Na excretion. Channel activity will be measured as amiloride-sensitive whole-cell currents in the renal cortical collecting tubule as well as the medullary collecting duct and the connecting tubule to quantitate its contribution to renal Na handling. We will further test for the importance of Na channels by measuring Na excretion in rats treated with the channel blocker amiloride. Upregulation of other transport pathways will also be examined using thiazides to block NaCI cotransport and angiotensin receptor antagonists to prevent upregulation of Na/H exchange. We will also assess the roles of two putative signaling pathways for aldosterone secretion under these conditions, increased renin activity and elevated plasma K. We will explore the mechanisms of pathological upregulation seen in the Liddle's Syndrome form of human hypertension. This will be done using mice in which the channel subunit B-ENaC has been truncated to mimic the human mutation. Here we will test the idea that the mutation decreases the rate of downregulation of previously activated channels. Finally we will study the effects of insulin on the channels. We will examine the hypothesis that this hormone increases the open probability of channels inserted or activated by aldosterone. The results should help to understand the role of channel-mediated Na reabsorption under conditions of physiological (dietary) stress and hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN AND SODIUM MODULATE HYPERTENSION IN AGING RATS Principal Investigator & Institution: Hinojosa-Laborde, Carmen; Associate Professor; Physiology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The Dahl salt sensitive (S) rat will be studied as an animal model of post-menopausal hypertension to investigate the mechanisms responsible for the hypertension. The pressor systems that will be evaluated are the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS). The role of estrogen, aging, and salt intake as modulators of these pressor systems via their effects on the nitric oxide (NO) system will be investigated. The first specific hypothesis is that the aging process with the accompanying loss of estrogen activity is associated with a down regulation of the nitric oxide system resulting in hypertension. To test this hypothesis, Specific Aim 1 of this study is to monitor blood pressure and the level of activation of the NO system in intact, ovariectomized (OVX), and OVX+estrogen-treated Dahl salt sensitive and Dahl salt-resistant (R) female rats as they age from 3 month to 2022 months of age. The second specific hypothesis is that the factors maintaining the hypertension associated with the loss of estrogen activity in Dahl S rats is determined by the level of salt intake. OVX performed at young, middle and old age will cause an increase in blood pressure, but the rise will be attenuated with increasing age. However, the level of blood pressure and the activity of the pressor systems contributing to hypertension will be higher pre-OVX because of the effects of aging on the RAS and
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SNS. Two specific aims will address this hypothesis. Specific Aim 2 will be to establish that the Dahl S elderly and OVX females maintained on low salt intake will become hypertensive as a result of an activation of the RAS. Estrogen administration will maintain activation of the NO system to suppress the RAS. Blockade of NO formation in low salt animals will increase RAS function, especially in the OVX+estrogen animals. Specific Aim 3 is to determine that high salt fed Dahl S elderly and OVX animals will develop a hypertension that is dependent on the activation of the SNS. As with the low salt animals, estrogen supplement will suppress the SNS stimulation through a NOmediated mechanism. Together these studies will provide evidence that the arterial pressure of the Dahl S rat is sensitive to the removal of estrogen through OVX or aging suggesting a useful model of post-menopausal hypertension. By investigating the relationship of estrogen, NO and salt, important new information will be gained in the mechanisms whereby estrogen provides protection against hypertension. Importantly, a greater understanding will be obtained addressing why the protection disappears with the aging process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXTRACELLULAR MATRIX IN RENAL FIBROSIS Principal Investigator & Institution: Fogo, Agnes B.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-MAR-2007 Summary: Description (provided by applicant) Transforming growth factor-beta 1 (TGFbeta) has been implicated as a key molecule in fibrosis, and its expression is increased in numerous fibrotic conditions. The relationship of TGFbeta to other profibrotic mechanisms, such as angiotensin and plasminogen activator inhibitor-1 (PAI-1), and the differential role of infiltrating versus parenchymal cells are complex. TGFbeta can be locally activated by alphavbeta6, which is an integrin heterodimer that is expressed in epithelia in lung, skin and kidney and mediates cleavage of TGFbeta from latency associated peptide. Mice deficient in avB6 lack the ability to activate local TGFbeta through this alphavbeta6 integrin dependent mechanism and had marked protection against fibrosis in the unilateral ureteral obstruction model, with decreased PAI-1 expression, despite robust infiltration of macrophages. A full fibrotic response was restored by infusion of angiotensin or aldosterone, together with restoration of local increase of PAI-1. These projects will examine the TGFbeta1 dependent and independent mechanisms of fibrosis. We hypothesize that PAI-1 induction occurs even in the absence of local TGFbeta, and that PAI-1 by itself can effect fibrosis. We further hypothesize that both parenchymal and infiltrating cell mechanisms are necessary for full fibrotic response. We postulate that injury promotes epithelial-mesenchymal transdifferentiation, and that inadequate macrophage clearance of apoptotic cells both contribute to fibrosis. We will use the alphavbeta6 knockout mouse and bone marrow transplant, to experimentally manipulate parenchymal versus infiltrating cells combined with pharmacological manipulations, to determine mechanisms of interstitial fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FETAL ORIGINS OF ADULT HYPERTENSION IN MICROSWINE Principal Investigator & Institution: Bagby, Susan P.; Professor of Medicine; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 31-DEC-2007
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Summary: (provided by applicant): Human cardiovascular disease, including hypertension, has been linked by epidemiologic studies to low birth weight. Microswine offspring of 1% Maternal Protein Restriction (MPR), applied during last third of gestation plus first two wks of lactation (nephrogenic period), exhibit early asymmetric growth retardation, reduced nephron number, rapid catch-up growth, and adult hypertension (HTN); single-nephron hyperfiltration maintains normal total kidney function. Adult Low-Protein Offspring (LPO) show key Renin/AnglI (RAS) abnormalities vs Normal-Protein Offspring (NPO): 1) elevated intrarenal AnglI, suggesting increased AnglI generation; and 2) increased renal microvascular contractile reactivity to AnglI despite reduced AT1 receptor (AT1R) density, suggesting postreceptor enhancement of AT1R contractile signaling efficiency. Aim 1 will test the hypothesis that MPR leads to HTN via increased generation of intrarenal AnglI in adult LPO. SubAims will test whether: 1A) MPR-related HTN is associated with in vivo ECV excess; 1B) MPR leads to intrarenal AnglI excess or activates AnglI-generating elements: renin, angiotensinogen (Aogn), AnglI Converting Enzyme (ACE); and 1C) MPR induces increased renal vascular contractile reactivity to AnglI, either by reduced endothelial relaxation and/or by enhanced post-receptor signaling [via classic AT1R contractile pathways vs AT1R-dependent EGFR transactivating pathways]. In other states of noninflammatory nephron deficit, compensatory single-nephron hyperfiltration - designed to maintain adequate protein/nitrogen excretion - requires intrarenal Renin/AnglI (RAS) activation. Thus, AIM 2 will test the hypothesis that Body-Size Excess relative to reduced nephron number - developing during rapid catch-up growth - induces the hemodynamic and RAS abnormalities in adult LPO. SubAims will test whether prevention of body size excess (by caloric restriction to maintain body wt percentile at the neonatal level) prevents: 2A. HTN/ECV excess/nephron hyperfiltration; 2B. intrarenal AnglI excess and/or activation of AnglI-generating elements; and 2C. increased renal vascular reactivity to AnglI. AIM 3 will test the hypothesis that effects of MPR and/or Body-Size Excess are mediated by the AT1 receptor. Subaims will test effects of in vivo AT1R blockade or placebo 3A. on hemodynamic and 3B. on AnglI contractile signaling via classic and EGFR-transactivation routes (using renal vascular reactivity and activated vs total signaling protein abundance in fresh vascular/cortical tissues). Studies address a worldwide health risk, test interventions (weight control/AT1R block) of potential clinical value, and impact the current pediatric practice of promoting catch-up growth in low-birth-wt infants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION AND RENAL REGULATION X/K -ATPASE ISOFORMS Principal Investigator & Institution: Kone, Bruce C.; James T. and Nancy B. Willerson Chair; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-JUL-2005 Summary: The H+ -K+ -ATPase alpha2 (HKalpha2) gene expressed in kidney and colon plays a critical role in the maintenance of body potassium and acid-base balance during chronic hypokalemia and chronic sodium depletion. The broad objectives of the proposed research are to identify the molecular mechanisms underlying the transcriptional regulation of this gene in the kidney and colon during these commonly encountered clinical conditions. Data are presented to indicate that the HKalpha2 gene is differentially regulated at the transcriptional level in the renal outer medulla and distal colon in response to chronic hypokalemia and states of aldosterone excess, respectively. The proposal examines the hypothesis that specific transcription factors
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selectively expressed or induced in these tissues interact with cis- regulatory elements to control HKalpha2 gene expression. The structural organization and precise chromosomal position of the murine HKalpha2 gene will be characterized. The selective effects of mineralocorticoids and glucocorticoids on HKalpha2 transcription in the distal colon and kidney will be analyzed to determine whether transcriptional induction is specific to the cognate nuclear receptors for these ligands. DNase I hypersensitivity assays and in vivo footprinting coupled with analysis of HKalpha2 regulatory regionreporter gene constructs will be used to map, at single nucleotide resolution, cellspecific promoter and enhancer elements in epithelial cell lines derived from the renal medullary collecting duct and distal colon under normal conditions and in response to low external K+ and aldosterone. Gel shift and supershift assays of nuclear extracts will be used to identify further the trans-acting factors responsible for HKalpha2 transcriptional control. The ability of the nuclear proteins to alter HKalpha2 promoter/enhancer in trans will be tested in coexpression experiments. Studies in transgenic mice will test whether candidate regulatory elements identified in vitro faithfully mirror the tissue expression and responses to chronic K+ - or Na+-deprivation, and aldosterone excess of the endogenous HKalpha2 gene. The results of these studies should provide important molecular insights into the regulation of the HKalpha2 gene and its unique roles in renal and intestinal cell biology and pathobiology. The proposed studies should also yield fundamental information that can be more broadly applied to the Na+-K+-ATPase/H+-K+-ATPase multi-gene family, the molecular basis for tissuespecific gene regulation, and the molecular mechanisms responsible for selective steroid action on target genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ARCHITECTURE OF PLASMA T-PA AND PAI-1 Principal Investigator & Institution: Moore, Jason H.; Associate Professor; Molecular Physiol & Biophysics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Abnormalities in the plasminogen activator system have been implicated in the pathogenesis of arterial and cerebral thrombosis. In particular, elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (TPA), NAD T-PA/PA-1 complexes have been found to correlate with increased risk of myocardial infarction (MI) and/or stroke. Vascular fibrinolytic balance is, to a large part, determined by the competing effects of t-PA and PAI-1, and reflects a complex interplay between genetic and environmental factors. The present collaboration focuses on the common hypothesis that the association between activation of the reninangiotensin-aldosterone system (RAAS) and atherothrombotic events derives from an interaction between the RAAS and the fibrinolytic system. The collaborative atherothrombotic events derives from an interaction between the RAAS and the fibrinolytic system. The collaborative team that we have assembled to test this hypothesis includes investigators from 3 continents (America, Europe, and Africa), from 5 academic institutions (Meharry Medical College, Vanderbilt University Medical School, University of Groningen, University of Ghana and the University of Michigan) and from multiple departments within these institutions. The individual investigators bring to this collaboration diverse and complementary skills in molecular biology, vascular biology, hypothesis-driven patient- oriented research, human genetics, and clinical and genetic epidemiology The proposal is comprised of 4 complementary projects: 1) Molecular Genetics of PAI-1 Expression, (DE Vaughan, PI); 2) Genes and
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Fibrinolytic Capacity of Human Endothelium, (NJ Brown, PI); 3) Genetic Architecture of Plasma t-PA and PAI-1, (JH Moore, PI); and 4) Genetic Variants and Thrombosis: The Renin-Angiotensin and Fibrinolytic Systems, (P Hebert, PI). The proposed molecular genetic methods, new transgenic mouse models, mechanistic human studies, and innovative study designs in genetic epidemiology promise to provide complementary data. Data derived from these studies are expected to yield new information regarding the mechanism of interaction of the RAAS and fibrinolytic systems. The collaboration takes advantage of existing DNA samples collected from American, European, and African population studies and intervention trials to test the hypothesis in groups of different ethnic background and cardiovascular risk. These population-based studies are expected to generate new hypotheses to be tested at the molecular level in cells and at physiological level in humans. This collaborative proposal provides a robust mechanism for highly focused translational research in the molecular genetics and biology of the role of the fibrinolytic system in arterial and cerebral thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC HYPERTENSION
DETERMINANTS
OF
RAA
SYSTEM
AND
Principal Investigator & Institution: Williams, Gordon H.; Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: (Adapted from the applicant's abstract) Despite intensive efforts, the primary mechanism(s) responsible for the pathogenesis of essential hypertension remain unknown. The knowledge that a large fraction of the populations' variation in blood pressure is genetically determined suggests the possibility of identifying the genetic variants which directly contribute to the pathogenesis of hypertension. Subdividing hypertensive patients by using intermediate phenotypes - traits which are found to be present in some, but not all, hypertensive subjects - has the potential to increase substantially the power of such genetic approaches. There are five aspects to this proposal. First, in the routine use of the "intermediate phenotype" to subgroup our hypertensive patients and thereby increase the likelihood of linking the consequent pathophysiology to (a) specific gene(s). Second, are the state-of-the-art clinical research facilities - General Clinical Research Centers (GCRCs) - in which to perform the detailed physiologic protocols. Third, they will concentrate on using association analysis of candidate genes with expression of intermediate phenotypes of hypertensive in subjects off medications, while continuing to use the techniques of affected sibling pairs and family linkage analyses. Fourth, is the documentation of genetic epistasis in this population when sub- grouped by intermediate phenotype. Thus, they expect to be able to tease out the polygenes contributing to hypertension and subsequently investigate how they interact with each other and with environmental factors. Finally, there are a large number of subjects who have already been studied. In total, we have DNA, demographic data, clinical data, and some biochemical data from over 2400 individuals belonging to 1215 pedigrees who were examined to qualify subjects for the inpatient GCRC studies. Those who have undergone our intensive intermediate phenotyping protocol include 91 individuals from 15 pedigrees, 145 sibships of two or more hypertensive siblings (193 sibling pairs), 175 hypertensive "singletons" and 79 normotensive "singleton". The overall objectives of this project are threefold: 1) to determine if the four potential intermediate phenotypes are associated with each other; 2) to identify the gene(s) associated and/or linked to these intermediate phenotypes;
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and 3) to determine the likelihood of genotype predicting phenotype for increased specificity for prevention and/or intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC EPIDEMIOLOGY AND RENAL ALLOGRAFT OUTCOMES Principal Investigator & Institution: Israni, Ajay K.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2008 Summary: (provided by applicant):The applicant is a nephrology fellow with advanced training in genetics and clinical epidemiology and a longstanding interest in clinical research. This application proposes a comprehensive, interdisciplinary program that will provide the applicant with the skills and experience necessary for his development into an independent investigator in renal, genetic epidemiology. The principal objective of this mentored training proposal is to acquire the necessary skills to become an independent clinical investigator and a genetic epidemiologist addressing important issues in renal transplantation. The training component of this program includes a preceptorship with Dr. Harold I. Feldman, Chief of Clinical Epidemiology, University of Pennsylvania and completion of the formal course work and dissertation leading to a Ph.D. degree in Epidemiology. The objective of the research component is to determine whether allelic variants of genes that are associated with development of essential hypertension are also associated with renal allograft survival.Hypertension has a substantial negative impact on renal allograft survival. Several genes that are associated with essential hypertension also play an important role in the modulation of immune response, growth factors and fibrosis. Understanding genetic variants of potential determinants of renal allograft survival may allow for treatments that extend the function of kidney allografts. The research aims will be acomplished via a multicenter, prospective cohort study among adult recipients of renal allografts in the Delaware Valley. The genetic polymorphisms of the following genes will be determined by PCR of DNA samples from the allograft recipients: angiotensin-converting enzyme, angiotensinogen, angiotensin II Type 1 receptor, aldosterone synthase and the Giprotein Beta-3 subunit gene. The selection of these genes is based on plausibility, potential causation, frequency of occurrence and previously published validation studies in related settings. A Cox proportional hazard model will be implemented to explore the relationship of the candidate gene polymorphisms with time to allograft loss. By identifying genetic polymorphisms that impact allograft survival, this study will help identify patients at risk and will help in the development of therapies targeting critical pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC EPIDEMIOLOGY OF HYPERTENSION IN AFRICAN AMERICAN Principal Investigator & Institution: Rotimi, Charles N.; Associate Professor and Director; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-JUL-2006 Summary: The goal of this project in genomic research is to contribute to the growing attempts to fill a major void in resources available to the research community for dissecting the pathophysiology of hypertension (HTN) and related complications in African Americans. It is well documented that A experience one of the highest incidence of HTN in the world. Epidemiologic studies have demonstrated the important role of
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environmental factors including diet (e.g., high salt intake), lifestyle (e.g., lack of physical activity) and psycho-socio stressors (e.g., employment difficulty) in the etiology of HTN. However, a proportion of the total variance remains unexplained. Because of the importance of family history and observed differential susceptibility to HTN, it is now widely accepted that the etiology of HTN is the result of complex interplay of genetics and the environment. Based on an on-going family study, we propose to recruit a population of 350 AA families with 5 or more members (n> 1,750 persons) in Washington, DC. During a clinical exam, we will collect demographic data, measure BP, height, weight, fat mass, fat free mass, waist and hip circumference. Blood will be drawn for assays of physiologic intermediates including components of the renin-angiotensin aldosterone system (RAAS-Angiotensinogen-AGT, angiotensin-converting enzyme aldosterone system (RAAS-Angiotensinogen-AGT, angiotensin-converting enzymeACE and aldosterone), endothelin 1, C-reactive protein (CRP), sodium potassium, calcium, albumin, creatinine, glucose, insulin and leptin. Genomic DNA will be extracted. We propose to evaluate the association and linkage between BP, HTN and genes of the RAAS (ACE, AGT and angiotensin II receptor type 1), epithelial sodium channel beta subunit, endothelial nitric oxide synthase, CRP, endothelin 1, and beta2adrenergic receptor. We will evaluate single nucleotide polymorphisms (SNP) variations in candidate genes and determine if variation in each SNP and in constructed haplotype, explain variations in BP and HTN risk. In addition, DNA will be stored for future application to conduct genome-wide scan with the goal of identifying novel genomic regions in linkage and association with BP and HTN in AA. Identified novel genomic regions may inform our understanding of the etiology of HTN in other human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC HYPERTENSION
INTERACTIONS
IN
ATHEROSCLEROSIS
AND
Principal Investigator & Institution: Maeda, Nobuyo; Professor; Pathology and Lab Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: The goal of our proposed research is to increase our understanding of the factors leading to the interrelationship between atherosclerosis and hypertension. Using a combination of mechanical and genetic manipulations in a mouse model of atherosclerosis, we will assess the relative influence on atherogenesis of direct physical changes in blood pressure versus genetic changes in systemic vasoactive mediators or in the factors that affect local responsiveness of vascular tissues. Specific aim (i) is to determine the effects at different stages of lesion development in the carotid arteries of a superimposed mechanical increase (right) or decrease (left) in pressure consequent to aortic arch coarctation. Specific aim (ii) is to determine whether the effects observed above can also be achieved by blood pressure changes as a consequence of genetically controlled changes in the expression of the systemic vasoactive mediator, renin. Specific aim (iii) is to determine the effects of mechanically-imposed changes in pressure on lesions in the carotid arteries of proatherogenic mice with additional genetic mutations that have local effects on vascular tissues via three different systems: (a) angiotensin II receptor type 1A, (b) endothelial nitric oxide synthase, and (c) natriuretic peptide receptor A. Better understanding of the effects on atherogenesis of the individual factors that affect blood pressures should help the development of new means for prevention and treatment of cardiovascular diseases.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC VARIANTS AND THROMBOSIS Principal Investigator & Institution: Hebert, Patricia R.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2005 Summary: Abnormalities in the plasminogen activator system have been implicated in the pathogenesis of arterial and cerebral thrombosis. In particular, elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and t-PA/PAI-1 complexes have been found to correlate with increased risk of myocardial infarction (MI) and/or stroke. Vascular fibrinolytic balance is, to a large part, determined by the competing effects of t-PA and PAI-1, and reflects a complex interplay between genetic and environmental factors. The present collaboration focuses on the common hypothesis that the association between activation of the reninangiotensin- aldosterone system (RAAS) and atherothrombotic events derives from an interaction between the RAAS and the fibrinolytic system. The collaborative team that we have assembled to test this hypothesis includes investigators from 3 continents (America, Europe, and Africa), from 5 academic institutions (Meharry Medical College, Vanderbilt University Medical School, University of Groningen, University of Michigan and University of Ghana) and from multiple departments within these institutions. The individual investigators bring to this collaboration diverse and complementary skills in molecular biology, vascular biology, hypothesis-driven patient-oriented research, human genetics, and clinical and genetic epidemiology. The proposal is comprised of 4 complementary projects: 1) Molecular Genetics of PAI-1 Expression, 2) Genes and Fibrinolytic Capacity of Human Endothelium, 3) Genetic Architecture of Plasma t-PA and PAI-1, and 4) Genetic Variants and Thrombosis: The Renin-Angiotensin and Fibrinolytic Systems. The proposed molecular genetic methods, new transgenic mouse models, mechanistic human studies, and innovative study designs in genetic epidemiology promise to provide complementary data. Data derived from these studies are expected yield new information regarding the mechanism of interaction of the RAAS and fibrinolytic systems. The collaboration takes advantage of existing DNA samples collected from American, European, and African population studies and intervention trials to test the hypothesis in groups of different ethnic background and cardiovascular risk. These population- based studies are expected to generate new hypotheses to be tested at the molecular level in cells and at a physiological level in humans. This collaborative proposal provides a robust mechanism for highly focused translational research in the molecular genetics and biology of the role of the fibrinolytic system in arterial and cerebral thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENOMIC & NONGENOMIC EFFECTS OF STEROIDS ON SALT INTAKE Principal Investigator & Institution: Sakai, Randall R.; Associate Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 31-MAR-2005 Summary: (applicant's abstract): The expression of sodium appetite in the rat is controlled by a multitude of hormonal mechanisms evoked when the animal is sodium depleted. Research has shown that it is not the sodium deficiency itself but rather the synergistic action of angiotensin and aldosterone, hormones that are released in
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response to the sodium depletion, which 1) generate the appetite for salt, and 2) have long-term effects that enhance subsequent salt intake. The proposed experiments examine the genomic and non-genomic effects of steroids on sodium intake and are based upon a foundation of past research examining the neurohormonal basis of sodium intake in the rat. This research proposal attempts to extend the current understanding of how and where these hormones act in the brain to elicit their specific behavioral effects by using A) site specific directed stimulation of brain parenchyma by steroids to: 1) identify those brain areas sensitive to adrenal steroids in eliciting sodium intake, and 2) to examine the mechanism by which the steroids act, i.e., either by classical genomic actions on the neurons that require hours of activation prior to eliciting a behavioral response or by acting at putative membrane receptors such that changes in behavior occur within minutes after steroid application; and B) by using current cell and molecular biological techniques in an in viva preparation to examine the effects of selective interference of endogenous steroid and peptide receptor production in brain. In addition to increasing our understanding of a classic instance of self-regulatory behavior, this research has health relevance. These results may provide rational therapies for patients in whom sodium intake complicates the management of hypertension and renal disease. With a better understanding of how endocrine mechanisms operate in eliciting sodium intake, chemical therapies that interfere with the actions of the/hormones can be directed at different levels of its production or mechanisms of action to reduce the craving for sodium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEME-HEME OXYGENASE-CARBON MONOXIDE SYSTEM IN HYPERTENSION Principal Investigator & Institution: Johnson, Fruzsina K.; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: Carbon monoxide (CO) can be endogenously formed during the enzymatic degradation of heme by heme oxygenase (HO). Although CO is generally regarded as a vasodilator, by its inhibitory effect on nitric oxide synthase it is also a vasoconstrictor. On high salt diet Dahl salt-sensitive rats (DS) develop hypertension that is accompanied by decreased NO formation. This project will investigate the role of the vascular hemeHOCO system in endothelial dysfunction during salt-induced hypertension in DS rats. The following specific aims will be addressed: Aim1: Characterize the temporal changes in various indeces of the HO system, arteriolar NO function, and cardiorenal pathologies in DS and salt-resistant (DR) rats on high and low salt diets. Aim2: Determine the effects of genetic predisposition for salt-sensitivity, high salt diet, and hypertension on various indeces of the HO system, arteriolar NO function, and cardiorenal pathologies in DS and DR rats. Aim3: Establish the effects of altered HO system function on artedolar NO function, and cardiorenal pathologies in DS and DR rats on high and low salt diets. Methods: Some animals will receive antinhypertensive treatment, others pressor treatment. Some groups will be treated with heme-L-lysinate, others with zinc protoporphyrin IX to increase or decrease endogenous CO formation, respectively. HbCO will be measured with a clinical grade analyzer (OSM3). Vascular HO-1 protein content will be studied by Western-blotting and immunohistochemistry (ABC method). NO function will be examined in isolated skeletal muscle arterioles by studying responses to a NO synthase inhibitor, an endothelium-dependent vasodilator, and a NO donor. Internal diameter of pressurized arterioles will be measured with a microscope and a video caliper. Objectives: These studies will provide information on
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temporal changes in HO function, cardiorenal pathologies and arteriolar NO function during salt-induced hypertension. Furthermore, they will evaluate the factors (genetic salt-sensitivity, high salt diet, and/or hypertension) contributing to HO-mediated NO dysfunction during salt-induced hypertension in DS rats. They will also examine the effects of altered endogenous CO formation on arteriolar NO function and cardiorenal injury in DS rats during salt-induced hypertension. Understanding the pathological basis of endothelial dysfunction may help to develop causetargeted therapy resulting in prolonged survival of hypertensive patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HISTO-MECHANICS HYPERTENSION
&
BIOLOGY
OF
REMODELING
IN
Principal Investigator & Institution: Humphrey, Jay D.; Professor; Biomedical Engineering; Texas Engineering Experiment Station Mail Stop 3000 College Station, Tx 778433000 Timing: Fiscal Year 2002; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Hypertension remains as a major risk factor for a multitude of cardiovascular diseases, and as such it is responsible for significant morbidity and mortality. Recent advances in vascular biology and mechanics suggest a paradigm shift in hypertension research. It is now clear that focusing on local regulatory activities of the vascular wall that are controlled by mechanotransduction mechanisms promises significantly increased understanding. In this proposal, we will focus on the molecular mechanisms of vascular adaptation in coronary and cerebral arteries and arterioles, and the associated integrated manifestations in vessel morphology and function at the cellular and tissue levels. Toward this end, we have developed a new micro-pig model of renovascular hypertension that allows us to detail the time-course of hemodynamic changes during the development and reversal of the hypertension. Using an externally controllable suprarenal aortic coarctation model, we will delineate between purely mechanical effects and those due to engaging the renin-angiotensin system. This will allow us to explore the hypothesis that the efficacy of pharmacological therapy depends strongly on the target vascular bed and the time that the intervention is initiated during the development of the hypertension. The overall working hypothesis is that hypertension-induced alterations in cell function and matrix biology are largely due to changes in the pointwise multiaxial stress field. Specifically, we hypothesize that altered stresses (intramural and wall shear) induce (1) changes in the local expression of nitric oxide and angiotensin, (2) downregulation of potassium-sensitive ATP channels and adenosine receptor subtypes, (3) increases in RGD integrin binding sites in the matrix, similar to those in a wound healing response, and (4) spatial and temporal differences in apoptosis and the production of growth factors and proteases. These effects, balanced by a resetting of the barorecptor reflex, shear stress regulation of endothelial activity, and the myogenic response together result in the bed-specific adaptation. These hypotheses will be tested by combining clinical, molecular, cell biological, immunohistochemical, morphological, and biomechanical methods to study 5-8 vessels at multiple times during the development and reversal of hypertension in a single animal model, although there are many calls in the literature for multidisciplinary attacks on the problem of hypertension, this study will be the first to collect and synthesize such broad data. Indeed, given the vast amount of data, we suggest that combining three recently, separate theoretical developments by members of our team will enable us to develop mathematical models that synthesize the data and provide predictive capability. The latter will enable the exploration of further hypotheses in an
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Aldosterone
efficient manner and guide pharmacologic delivery strategies. Years 1-2 will focus on the time-course of changes due to the development of hypertension whereas years 3-5 will focus on the time-course of changes due to reversing the hypertension either mechanically or via specific pharmacological agents, both as a function of the time during the development that the intervention is initiated. Subsequent parallel studies will focus on additional pharmacological agents and gender-related differences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL REGULATION OF ANGIOTENSIN RECEPTORS Principal Investigator & Institution: Sandberg, Kathryn L.; Professor; Medicine; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The sexual dimorphism associated with many cardiovascular and renal diseases related to aging is well documented with the risks being significantly higher for men than women. Two of the major risk factors in these diseases are felt to be increased activity of the renin angiotensin system (RAS) and estrogen deficiency. Furthermore, there is accumulating evidence that estrogen may have a regulatory influence on the RAS. In view of its considerable potential physiologic and pathophysiologic significance, we propose to investigate how estrogen regulates the activity of the RAS. Specific hypotheses to be tested in the proposed studies are: 1) estrogen down- regulates the density of the type 1 angiotensin receptor subtype (AT1) expressed in adrenal and kidney tissues and thereby attenuates tissue responsiveness to the hormone, angiotensin II (Ang II); 2) estrogen mediates its effects on AT1 receptor AT1 receptor expression in these tissues via the estrogen type (3 (ERs) receptor; 3) estrogen has direct effects on AT1 receptor expression by modulating receptor transcriptional and/or posttranscriptional mechanisms; 4) estrogen also acts to decrease AT1 receptor expression by modulating the local production of Ang II; and 5) the ability of estrogen to down-regulate Ang II activity in the adrenal and kidney is attenuated in animal models of salt-sensitive hypertension and aging. Our first aim is to determine the effects of estrogen on AT1 receptor density in the adrenal and kidney of the rat using quantitative autoradiography under a variety of perturbations of the RAS. In Aim 2, we will determine the effects of estrogen on adrenal and kidney tissue responsiveness to Ang II by measuring the effects of estrogen on Ang II-induced changes in aldosterone secretion and renal hemodynamics. Our third aim will focus on determining the specific mechanisms by which estrogen reduces the density of AT1 receptors. We will examine the effect of estrogen on AT1 receptor synthetic and degradative pathways and examine its effects of on the components of the plasma and tissue RAS. We will also determine which estrogen receptor subtype mediates the effects of estrogen. In the last aim, we will study the effects of estrogen on adrenal and kidney AT1 receptor density and function in relevant animal models of salt-sensitive hypertension and aging. Our studies will therefore answer important questions about whether some of the well-documented cardio- and renal- protective effects of estrogen may occur via down-regulation of AT1 receptors in the adrenal and kidney, two key effector organs of the RAS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONE IN SALT SENSITIVITY AND HYPERTENSION Principal Investigator & Institution: Chandramohan, Gangadarshni; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 900593025 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008
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Summary: High blood pressure (HBP) is known to be one of the leading causes of cardiovascular disorders in the US and occurs at disproportionately high rates in ethnic minorities. While salt sensitivity has been established as an important factor in the prevalence and severity of hypertension in humans, the underlying pathophysiology is not well identified. In addition, salt sensitivity is more prevalent among African Americans and has been postulated to contribute to both hypertension and hypertensive nephropathy. Animal models provide excellent opportunities for examining specific regulatory systems that can then be translated into clinical trials. Studies by the investigator's previous group have shown that Gamma Melanocyte Stimulating Hormone (gammaMSH), a potent natriuretic peptide, plays a role in normal sodium homeostasis in rats. They demonstrated that Sprague Dawley (SD) rats have increased pituitary prohormone proopiomelanocortin (POMC) and protease convertases (PC1 and PC2 that process the POMC into [gammaMSH) mRNA expressions along with an increase in plasma gammaMSH level at 3 weeks of chronic salt loading, suggesting a possible role of this system (gammaMSH system) in sodium homeostasis. Our lab has recently demonstrated an increase in both POMC message expression and plasma gammaMSH levels in Wistar Kyoto (WKY) rats fed with high salt diet (HSD; 8% NaCI) compared to WKY rats fed with low salt diet (LSD; 0.3% NaCI) diet. This result is consistent with that of SD rats from previous studies. By contrast, we observed blunting of POMC mRNA expression along with inappropriately high levels of plasma gammaMSH in SHR fed with HSD compared to SHR fed LSD. Based on these findings we postulate that the increase of plasma gammaMSH level with decreased POMC message expression in SHR HSD rats is due to melanocortin receptor (MCR) resistance to gammaMSH in the kidneys induced by HSD. This resistance subsequently leads to high levels of plasma gammaMSH and feedback suppression of POMC mRNA expression. Thus, the specific aims of this study are: 1) To examine the effect of dietary salt on renal MC3 receptor mRNA expression in the kidneys of SHR rats. 2) To examine the response of blood pressure, MC3 mRNA expression and rate of sodium (Na) excretion to exogenous gammaMSH in SHR rats when fed a high salt diet. 3) To examine the changes in blood pressure, MC3 receptor mRNA expression and rate of Na excretion following administration of MC3 receptor antagonist and agonist in SHR rats receiving high salt diet. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF NOVEL CANDIDATE SALT-SENSITIVITY GENES Principal Investigator & Institution: Danziger, Robert S.; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Dietary salt has a major impact on blood pressure in many patients and is considered to be an important environmental risk factor for hypertension. Understanding the genetic underpinnings causing hypertensin is a necessary step for developing novel and customized therapeutic strategies for hypertension. We hypothesized that genes important in salt-sensitivity and hypertension might be discovered by identifying genes that undergo changes in abundance in normotensive rats when subjected to a high salt diet-- but do not undergo the same change abundance in rats that become hypertensive on a high salt diet. To distinguish such genes, we applied transcriptional profiling, a powerful new technology in which the abundance of thousands of genes is simultaneously measured, to Sprague Dawley and Dahl salt-sensitive (Dahl SS/Jr) rat strains on 0.4% and 8% NaCI diets. We
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identified 26 genes that meet this criteria from over 5,000 genes profiled. 2 of these 26 genes, i.e., aminopeptidase N, serum and glucocorticoid inducible kinase-1 (SGK), directly impact on the renin-angiotensin-aldosterone signaling pathway (RAS). The purpose of this proposal is to test the hypothesis that genes for aminopeptidase N and SGK contribute salt-sensitive hypertension in the Dahl rat. Supportive preliminary data shows corresponding changes in abundance of proteins coded for by these genes in the kidneys and that the genes map to known quantitative trait loci (QTLs) for blood pressure. Aim 1 is to determine whether there is preferential association of specific aminopeptidase N and SGK gene polymorphism(s) in Dahl SS/Jr compared to Dahl saltresistant (SR/Jr) rat strains. Specific Aim 2 is to determine whether candidate genes cosegregate with salt-sensitive hypertension. Specific Aim 3 is to determine saltsensitivity in congenic Dahl SS/Jr with chromosomal segments from Dahl SR/Jr rats containing SGK and aminopeptidase N genes introgressed. In this Aim, we will develop congenic lines of Dahl SS/Jr introgressed with SR/Jr regions containing aminopeptidase N and SGK genes. This is a first step in the goal of developing novel and customized therapeutic approaches to hypertension based on genetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: KINASE REGULATION OF THE EPITHELIAL SODIUM CHANNEL Principal Investigator & Institution: Lebowitz, Jonathan J.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Dr. Lebowitz is currently conducting research in the laboratory of John P. Johnson at the Univeristy of Pittsburgh. His career goals for the period of this grant are to further develop both the technical expertise (e.g. in molecular, biochemical, and electrophysiological methods) and in the creative skills necessary to become a successful independent investigator. After 1-2 years of mentored research he plans to make the transition to a tenure-track faculty position within the renal division. His long term goal is to become a fully independent academic investigator performing basic research in an environment where bench results may be applied to important clinical problems within the broad fields of nephrology and cellular physiology. He is especially interested in the regulation of epithelial transport systems. The basis for this research project is a the discovery of a novel interaction between the beta subunit of the kinase that cleaves the inhibitor of nuclear factor kappa B (IKKbeta) and the beta subunit of the epithelial sodium channel (ENaC). Using the yeast two hybrid system and immunoprecipitation techniques, we have established this interaction. Further, using the two electrode voltage clamping technique and co-expression of IKKbeta and all three ENaC subunits in Xenopus oocytes, we have shown that this interaction increases ENaC activity. Although studies have linked activation of nuclear factor kappa B (NF-kappaB) with changes in ENaC activity, no study has elucidated the nature of this relationship nor has any research explored the basic mechanism involved. Since our results show that ENaC may be activated through the NF-kappaB cascade as well as regulated by glucocorticoids and mineralocorticoids, an interaction between these two pathways is apparent. Preliminary data demonstrates that mineralocorticoids may also activate pathways in renal and pulmonary epithelia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LOW-RENIN HYPERTENSION IN AFRICAN AMERICANS Principal Investigator & Institution: Pratt, John Howard.; Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 05-JUN-2001; Project End 31-MAY-2004 Summary: (Verbatim from the application): Low-renin hypertension is common in African Americans, with many failing to achieve a normal blood pressure despite the availability of a wide variety of antihypertensive agents. The low-renin state is consistent with increased retention of sodium. We have evidence that blacks have higher overall activity of the epithelial sodium channel (ENaC), a principal site for reabsorption of sodium within the kidney and where certain molecular mutations result in retention of sodium and severe low-renin hypertension (Liddle's syndrome). ENaC is upregulated by aldosterone. In the present proposal, we will study the usefulness of two drugs that inhibit ENaC activity, spironolactone, an antagonist of aldosterone, and amiloride, a direct inhibitor of ENaC, in blacks with low-renin hypertension who have shown resistance to treatment. We will follow a simple protocol wherein we will study patients taking an optimal regimen of antihypertensive medication including a full dose of diuretic but in whom a normal blood pressure has not been achieved. The patients will be randomized to either spironolactone 25 mg per day, amiloride 10 mg per day, the combination of spironolactone 25 mg and amiloride 10 mg per day, or placebo for 9 weeks. In Specific Aim #1, we will test the hypothesis that drug-resistant, low-renin hypertensive blacks normalize their blood pressure in response to treatment with small doses of agents that reduce ENaC function. We will also test for a synergistic effect of spironolactone with amiloride to lower blood pressure. In Specific Aim #2, we will test the hypothesis that the mechanism whereby the anti-ENaC drugs lower blood pressure is by reducing an intrinsically higher level of ENaC function, as evidenced by lower levels of renin and aldosterone at baseline and greater increments during treatment in responders. In Specific Aim #3, we will test the hypothesis that blood pressure responses to spironolactone are related to the presence of molecular variants in ENaC subunits, variants that have been shown previously to associate with level of blood pressure. In summary, we explore unique but simple approaches to treatment of lowrenin hypertension in blacks, a treatment modality that could prove useful to many patients currently with uncontrolled blood pressure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM ALDOSTERONE
OF
MECHANORECEPTOR
INHIBITION
BY
Principal Investigator & Institution: Drummond, Heather A.; Physiology and Biophysics; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2006 Summary: (provided by applicant): The long term objective of my lab is to understand the molecular basis of mechanotransduction. This includes the 1) identification of components of mechanosensitive ion channel complexes in sensory neurons and muscle cells, 2) regulation of mechanosensitive channel expression by physical and hormonal factors and 3) involvement in cardiovascular pathophysiology (autonomic dysfunction, hypertension). The current proposal will address a highly novel area of research: aldosterone regulation of mechanosensitive ion channel expression and function. Hypertension and chronic heart failure are characterized by elevations in circulating aldosterone. Aldosterone is known to inhibit baroreceptor function, which may
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contribute to cardiac arrhythmias frequently associated with these diseases. The molecular mechanism of aldosterone suppression of baroreflex control of the autonomic nervous system is unclear. The hypothesis underlying this proposal is that aldosterone activation of the MAPK signaling pathway, decreases the expression of mechanosensitive channels in baroreceptor neurons by inhibiting transcription and augmenting degradation of ENaC proteins, thus causing baroreceptor dysfunction. This is a novel hypothesis. The goals of this proposal are to determine if 1) aldosterone inhibits DEG/ENaC transcript expression and mechanically gated calcium transients, 2) activation of the MAPK signaling cascade inhibits ENaC expression and mechanically gated calcium transients, and 3) ENaC proteins are required for mechanosensory function in cultured sensory neurons. We will use real time RT-PCR and immunofluorescence to determine the role of aldosterone and MAPK pathway on ENaC expression in cultured sensory neurons. We will use 2 assays to assess mechanosensory function in cultured sensory neurons. The importance of ENaC proteins in mechanotransduction will be determined using interference RNA and overexpression of dominant-negative isoforms. The results from this proposal may help define the molecular mechanism of baroreceptor inhibition by aldosterone and provide a better understanding of the mechanism of autonomic dysfunction in hypertension and chronic heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS FOR CARDIOVASCULAR CONTROL EARLY IN DIABETES Principal Investigator & Institution: Brands, Michael W.; Professor; Physiology and Endocrinology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2003; Project Start 01-JAN-1997; Project End 31-MAR-2007 Summary: (provided by applicant): We have shown that hyperglycemia at the onset of Type I diabetes causes significant hypertension if it is induced in rats with chronic blockade of nitric oxide synthesis. The hypertension is prevented by blocking angiotensin II, or the sympathetic nervous system; but our data suggest the two systems are linked in this response and may involve superoxide and thromboxane. Blood pressure and nitric oxide also track closely with GFR. The studies in this proposal will test the central hypothesis that nitric oxide protects against hypertension at the onset of diabetes by counteracting pressor actions of the sympathetic and renin-angiotensin systems. The Specific Aims are: 1) to test the hypothesis that nitric oxide protects against AngII-induced hypertension at the onset of diabetes by: a) chronically clamping (fixing) renin-angiotensin system activity at normal levels;b) blocking AngII action in rats with chronic intravenous and intrarenal i) ramipril and ii) iosartan; c) blocking AngII action in mice with ACE gene knockout; d) determining if gradual onset of diabetes causes the same renin secretion and blood pressure responses; e) determining whether low sodium intake increases the dependence of blood pressure on nitric oxide. 2) to test the hypothesis that the SNS contributes to the hypertensive response primarily through renal mechanisms. We will: a) determine the roles of a versus b receptors in mediating the renal, renin, and blood pressure responses:b) remove the renal nerves to test the role of the kidney in mediating the sympathetic pressor effect; c) determine if a decrease in ANG II is required for adrenergic blockade to prevent the hypertension; d) determine if the SNS effect is due to increases in SNS activity, or whether it plays a permissive role, 3) to test the hypothesis that nitric oxide counteracts AngII-dependent superoxide and thromboxane production to control blood pressure at the onset of diabetes. We will determine this by: a) "blocking" superoxide with a superoxide dismutase mimetic in rats
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and gene overexpression in mice; b) quantifying the degree to which AngII determines whether superoxide significantly affects blood pressure: c) determining if thromboxane receptor blockade will decrease blood pressure if superoxide is not increased: d) determining whether knockout of superoxide dismutase 1 exacerbates the hypertensive response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS LEADING TO ADRENAL ZONATION Principal Investigator & Institution: Rainey, William E.; Associate Professor; Obstetrics and Gynecology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract) The human adrenal cortex acts as a compound endocrine gland secreting mineralocorticoids and glucocorticoids. These steroids arise from distinct zones of the adrenal cortex that have both morphologic and biochemical differences. The long-range objectives of the proposed research are to define the mechanisms causing the functional zonation of the adrenal, which be traced to the zone-specific expression of the enzymes involved in adrenal steroidogenesis. This is particularly true for CYP11B2 (aldosterone synthase) and CYP 11B 1 (steroid 11 betahydroxylase) that are responsible for the final steps in the biosynthesis of aldosterone and cortisol and exhibit zone-specific expression in the glomerulosa and fasciculata, respectively. The mechanisms causing differential expression of CYP11B1 and CYP11B2 have not been defined due in part to the lack of appropriate in vitro model systems. Recent development of a human adrenocortical cell line (NCI-H295R) that grows as a monolayer and continues to produce mineralocorticoids and glucocorticoids has overcome this problem. The availability of these cells has allowed the applicant to propose three specific aims directed at defining the molecular mechanisms that control the zonal expression of human CYP 11B 1 and CYP 11B2. The goals of Specific Aims 1 and 2 are to identify specific cis-regulatory elements and trans-acting factors that enhance expression of human CYP 11 B2 in the glomerulosa and repress expression in the fasciculata. This will be accomplished by defining enhancer and repressor elements in the CYP 11 B2 5-flanking DNA and intronic sequences followed by identification of the trans-acting factors that bind these elements. The goals of Specific Aims 3 are to define the cis-elements and trans-acting factors that activate or inhibit CYP 11B 1 gene transcription and cause its zone-specific expression within the adrenal cortex. These newly defined genes will be studied with regard to their involvement in the expression ofCYP11B1 and CYP11B2 as well as their regulation in adrenal cells. The completion of these aims would add considerably to the understanding of adrenal zonation as well as the molecular mechanisms regulating two key enzymes involved in the synthesis of mineralocorticoids and glucocorticoids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF CVD AND ENDOTHELIAL DYSFUNCTION IN OBESITY Principal Investigator & Institution: Hsueh, Willa A.; Professor of Medicine and Chief; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Endothelial cell (EC) dysfunction occurs early in the process of insulin resistance and, indeed, may be an integral component of the
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dysmetabolic syndrome. We hypothesize that adipokines contribute to both insulin resistance and EC dysfunction, possibly by increasing sensitivity to Angiotensin ll (Angll), in part by altering the balance between the activity of the phosphoinositol-3kinase (Pt3K) and mitogen activated protein kinase (MAPK) pathways. As a result, the progression of insulin resistance to type 2 diabetes parallels the progression of EC dysfunction to atherosclerosis. Specific Aims will be to determine: 1) The relationship of circulating adipokines to EC function in insulin sensitive (IS) vs. insulin resistant (IR) Mexican Americans (MA). The IR MA will include the spectrum of insulin resistance: early IR, IGT, and type 2 diabetes. EC function will be measured by coronary PET scanning. 2) Whether IR subjects have increased sensitivity to AngII infusion vs. age and gender-matched IS subjects as measured by blood pressure, suppression of plasma renin activity, increasing circulating hsCRP and adipokine levels, and stimulation of plasma aldosterone 3) The effect of AnglI AT1 receptor blocker (ARB) administration on insulin-mediated glucose uptake, EC function, and circulating adipokines and inflammatory markers in IR subjects. 4) The correlations of insulin sensitivity and EC function with measurements of inflammatory gene expression, MAPK and PI3K activity in subcutaneous fat biopsies of IS vs. IR subjects and of (IR) subjects before and after treatment with an ARB. 5) The correlation of EC function with insulin sensitivity, circulating adipokines, and fat adipokine expression in the Zucker lean vs. obese rat models. The results of these investigations will help to 1) identify potential mechanisms by which adipokines alter signaling mechanisms and increase sensitivity to Angll to impair EC function and 2) determine the effect of RAS inhibition on adipokine levels and expression as related to insulin-mediated glucose uptake and EC function. These studies potentially have direct clinical applications as they promise to determine where in the spectrum of insulin resistance and EC dysfunction RAS inhibition is warranted to prevent development of the endpoints of diabetes and atherosclerosis. Early intervention is critical if we are to prevent these two major diseases, which may, indeed, be the same disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMBRANE TRAFFIC IN AVP RESPONSIVE RENAL TUBULE CELLS Principal Investigator & Institution: Wade, James B.; Professor; Physiology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-MAR-1984; Project End 31-DEC-2004 Summary: The long-term goal of this project is to understand the role of membrane traffic in the cellular actions of vasopressin AVP). Newly developed anti-peptide antibodies that are specific for UT-A3 and ROMK will be used to test the hypothesis that AVP acts on these transporters to cause trafficking to the plasma membrane acutely and an increase in their abundance with long-term exposure. New extremely sensitive methods will allow quantitative confocal and electron microscopic immunolocalization studies to test this hypothesis. Additional studies will use antibodies to different sites of UT-A1 to identify the cellular location of UT-A4 and UT-A2 in the descending thin limb of short loops of Henle. This will test the hypothesis that these isoforms function as surface specific urea transporters in this segment. Trafficking will also be tested using surface biotinylation of isolated suspensions of IMCD to monitor surface expression of UT-A3 in response to AVP. Similarly, we will use biotinylation of isolated preparations of cortical collecting ducts (CCD) to test if ROMK traffics to the surface with acute AVP exposure. This preparation will also be used to test if there are changes in the abundance of ROMK in CCDs with chronic adaptation due to AVP, high K diet and aldosterone.
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Other studies using amphibian oocytes will test the role of PKA site 525 in trafficking of ROMK using surface biotinylation. Co-expression of the PDZ protein NHERF2 and/or ezrin will be used to examine if these proteins alter surface expression of ROMK. This will test the hypothesis that NHERF2 participates in a signaling complex important for ROMK regulation. Other studies will use colocalization of transporters with established markers to identify which distal regions express ROMK and ENaC. Studies will also test the hypothesis that adaptations can induce expression in regions that normally have little or undetectable amounts of these transporters. This will provide unique data on whether chronic adaptations to AVP, K diet and aldosterone have effects on expression of these channels that have previously been detected for water channels in the connecting tubule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MINERALOCORTICOID HYPERTENSION
RECEPTOR
PHYSIOLOGY
IN
Principal Investigator & Institution: Geller, David S.; Assistant Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: (Adapted from the applicant's abstract) The human mineralocorticoid receptor (MR) serves as the final effector of the renin-angiotensin-aldosterone pathway and is a key regulator of sodium homeostasis in the distal nephron. These investigators recently described a novel form of human Mendelian hypertension caused by a gain of function mutation novel form of human Mendelian hypertension caused by grain of function mutation in MR. The mutation results in constitutive activity of the receptor and alters receptor specificity such that progesterone, normally an MR antagonist, functions as an agonist. Consistent with the dramatic rise in progesterone levels in pregnancy, carriers of this mutation develop severe pregnancy-related hypertension. Previous studies indicate that bending of helix 3, and that this mutant achieves the 210H independent bending of helix 3 via creation of a novel van der Waals interaction between helix 3 and helix 5. The observations that this helix 3- helix-5 interaction is highly conserved among diverse nuclear receptors indicated its general role in receptor activation. In this grant, we propose both biochemical and clinical studies to augment our understanding of MR function in human physiology and hypertension. They will assess the proposed model for MR activation and identify specific residues necessary for MR specificity and activity. Furthermore, they will identify nuclear co-regulators required for MR activity and identify the biochemical requirements for MR activation. Clinically, they propose to determine the prevalence of disease causing MR mutations in a variety of clinical situations and finally, determine extra-renal effects of an activated MR in patients carrying this mutation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSPORT
MINERALOCORTICOID-REGULATED
EPITHELIAL
SODIUM
Principal Investigator & Institution: Pearce, David; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Extracellular fluid volume in vertebrates is regulated primarily by the mineralocorticoid hormone, aldosterone, which stimulates Na+ absorption in tight epithelia, particularly the kidney collecting duct. This process plays a pivotal role in the
42
Aldosterone
control of blood pressure, and its dysregulation, either due to excess hormone or to target cell defects, is an important cause of hypertension. Although aldosterone is known to act through intracellular receptors to regulate gene transcription, the mechanistic basis of its effects on Na+ transport remains poorly understood. The earliest effect of aldosterone is to stimulate apical membrane ENaC insertion and/or increase ENaC open probability without altering ENaC subunit gene transcription. Recently, significant progress was made in understanding the molecular basis of aldosteroneregulated Na+ transport with the discovery that serum and glucocorticoid-regulated kinase (SGK) is an aldosterone-induced ENaC modulator. SGK mRNA and protein are rapidly increased by aldosterone in kidney collecting duct and wild type SGK stimulates ENaC-mediated Na+ current more than seven-fold in Xenopus oocytes. Interestingly, an SGK mutant that cannot bind ATP ("kinase-dead mutant") not only fails to increase Na+ current but actually decreases it. These opposite functional effects of wild type and mutant SGK are correlated with striking opposite effects on ENaC plasma membrane localization in oocytes. Moreover, antagonism of the phosphatidylinositol-3kinase (PI3K) signaling pathway has an effect on SGK activity and ENaC-mediated Na+ transport similar to the kinase-dead mutant. These findings strongly implicate SGK as an aldosterone-induced regulator of ENaC activity. However, it remains unknown how SGK modulates ENaC activity in CD cells and what role P13K plays in this process. With these observations in mind, the major goals of the work described in this proposal are to: (1) Determine if SGK is necessary and/or sufficient to mediate the effects of mineralocorticoids on Na+ transport in cultured CD cells. We will express wild type SGK and the kinase-dead mutant in cultured CD cells under the control of a heterologous promoter so that their levels can be controlled independently of mineralocorticoids and their selective effects on Na+ transport examined. We will also determine if mineralocorticoid-stimulated Na+ transport in collecting duct cells is delayed or blocked by disruption of SGK expression or activity. (2) Examine the role of ENaC phosphorylation and apical membrane relocalization in SGK- stimulated Na+ transport. We will determine if SGK directly interacts with and/or phosphorylates ENaC subunits. We will determine if SGK stimulates ENaC localization to the apical membrane of cultured cells. We will use mutagenesis to examine SGK structurefunction relationships in oocytes and cultured cells. (3) Examine the role of PI3K in activating SGK and in mediating the effects of mineralocorticoids on Na+ transport. We will examine the effect on ENaC-mediated Na+ transport of blocking PI3K activity. We will determine if constitutively active mutants of SGK, or downstream products of PI3K, overcome the effect of PI3K inhibition on Na+ transport. Together, these studies promise to lead to a greater understanding of the mechanistic basis of blood pressure regulation and potentially to new avenues of treatment for salt sensitive hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR AND PHYSIOLOGIC STUDIES OF A COLONIC K ATPASE Principal Investigator & Institution: Rajendran, Vazhaikkurichi M.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-1976; Project End 31-MAR-2004 Summary: This application proposes continuation of physiologic and molecular studies of potassium absorption in the rat distal colon. The PI has identified an active K absorptive process in the rat distal colon associated with an apical K/H exchange energized by a novel H,K-ATPase. The PI has also shown that this process is upregulated by both aldosterone and dietary K depletion. The PI's recent studies have
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focused on correlating the H,K-ATPase activity with the upregulation of K absorption both at the molecular and physiologic levels of study. The PI has reported that H,KATPase of rat distal colon is partially ouabain sensitive, pointing to the possible presence of two different potassium absorptive processes and H,K-ATPase isoforms. His group was recently successful in cloning the HCKalpha1 cDNA. The expression of this cDNA in SF9 cells showed ouabain insensitivity in contrast to studies from other groups using the oocyte expression system. In this proposal he, therefore, plans to determine the physiological function of the transporter cDNAs after transfection in a mammalian cell expression system. Studies are also proposed to determine whether the recently cloned rat colon-specific beta subunit is the elusive and putative beta subunit for optimal functional expression. The PI has identified an ouabain-sensitive K-dependent pHi recovery process in the colonic crypt. The PI hypothesizes that this pHi regulation will be modified by dietary K depletion and will, therefore, represent the second H,KATPase function. To identify the second colonic H,K-ATPase, the PI will use a cloning strategy based on its probable upregulation by dietary potassium depletion, its identity to the H-3 domain region rather than to the 5' end of HCKalpha1 cDNA and its exclusive localization in colonic crypts. It is also hypothesized that dietary potassium depletion might regulate the second colonic H,K-ATPase (HCKa2 and/or HCKab) at the apical membrane and/or electroneutral KCl cotransport at the basolateral membrane. The PI plans to employ cell and molecular biology studies to accomplish his four specific aims aimed at gaining more understanding of colonic potassium absorption. This proposal certainly has relevance to clinical medicine and would enhance our knowledge of potassium transport. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR RECEPTOR ACTION
MECHANISM
OF
MINERALOCORTICOID
Principal Investigator & Institution: Fejes-Toth, Geza; Professor; Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: The long-term objective of these studies is the understanding of the molecular mechanisms through which aldosterone stimulates Na transport and thereby regulates blood pressure. This project focuses on the initial nuclear events initiated by the hormone-liganded mineralocorticoid receptor (MR), in cells of its major target, the cortical collecting duct (CCD). The foundation of these studies is our recent observation that aldosterone induces MR clustering in the nucleus, whereas MR antagonists dissociate such clusters. Our studies also indicate that MR clusters are associated with the nuclear matrix but not with pallindromic hormone response elements. Our central hypothesis is that clustering of MRs is a critical step in the mechanism of action of aldosterone, and that foci of high MR density are also enriched in proteins involved in chromatin remodeling and in basal transcription factors. Consequently, the main goal of this project is to identify proteins interacting with the MR, that are responsible for its clustering and/or play a critical role in the major biological action of aldosterone. In aim 1, we will identify the nuclear subcompartment where the agonist-liganded MR clusters reside, and will determine which residues of the MR are involved in receptor clustering. These studies will employ side-directed mutagenesis of MR-green fluorescent protein chimeras, immunocytochemistry and confocal microscopy. Under Aim 2, we will identify and characterize proteins expressed in the CCD that directly interact with the agonist-liganded MR, using transcription- and signal transduction-based yeast twohybrid screens. We will identify regions of interaction of MR with MR-interacting
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Aldosterone
proteins (MRIPs), generate antibodies against MRIPs, and construct expression vectors capable of disrupting MR/MRIP interactions in vivo. In Aim 3, we will determine the role of MRIPs in MR clustering and in the biological responses initiated by aldosterone. We will determine the effects of manipulating the expression of MRIPs and disruption of their interaction with the MR, on aldosterone-induced receptor clustering, transcriptional regulation of an endogenous aldosterone target gene and on changes in Na transport in CCD cells. Identification of the molecular events involved in MR action should not only yield new insights into the mechanism of transcriptional regulation by aldosterone, but could also lead to the identification of genetic defects resulting in derangement of Na homeostasis, leading to hypertension (as in Liddle syndrome) or salt wasting (as in pseudohypoaldosteronism). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR REGULATION OF THE RENAL ALPHA2 H+, K+ ATPASES Principal Investigator & Institution: Cain, Brian D.; Professor; Biochem and Molecular Biology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Proton-potassium adenosine triphosphatases (H+, K+-ATPases) located in the renal collecting duct are involved in maintenance of blood K+ balance. Although aldosterone is known to be one of the principal regulators of K+ homeostasis and urinary acidification, no firm linkage has been established between aldosterone and the regulation of genes encoding the subunits of the H+, K+-ATPase or the activity of the pump in the kidney. The long term goal of our research is to gain an understanding of the regulation of H+, K+-ATPase activity in the kidney. At least three H+, K+-ATPases containing distinct isoforms of the alpha subunit populate the collecting duct. These H+, K+-ATPases contain the "gastric" 1, the "colonic" 2a or the novel 2b subunit. The 2b H+, K+- ATPase appears to be a candidate for the aldosterone-responsive form of the pump. We propose to study the expression of the 2a and 2b H+, K+- ATPases following two parallel lines of investigation. First, aldosterone-responsive transcriptional regulation of the 2b subunit will be investigated in vivo in a rabbit cortical collecting tubule cell line (RCCT-28A). This will be accomplished by characterizing the response of the 2a and 2b mRNAs, protein levels and H+, K+-ATPase activity following application of aldosterone to RCCT-28A cells. The elements governing transcription from the 2 gene will be located by DNase I hypersensitivity and promoter deletion analysis. The response elements will them be mapped to single-nucleotide resolution by in vivo footprinting studies. Second, the activity of the two 2 H+, K+-ATPases will be studied by expression of the cloned cDNAs in mammalian cells. A direct comparision will be made between the activities and pharmacological properties of the expressed 2a and 2b H+, K+-ATPases. Finally, phosphorylation of the 2 subunits will be investigated as a possible mechanism for differential regulation of the 2a and 2b H+, K+- ATPases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL MECHANISMS OF LONG-TERM CARDIOVASCULAR CONTROL Principal Investigator & Institution: Osborn, John W.; Professor; Animal Science; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 01-DEC-1999; Project End 31-JUL-2008
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Summary: (provided by applicant): We hypothesize that a central nervous system (CNS) "set point" exists for the long-term control of mean arterial pressure (MAP), and many forms of hypertension are due to primary resetting of the "CNS-MAP set point" by sodium retaining hormones such as aldosterone. We propose that this resetting occurs in response to hormonal activation of circumventricular organs (CVOs), which stimulate downstream sympathetic pathways by activation of amiloride-sensitive sodium channels. To test this hypothesis, we will use continuous 24hr/day recordings of MAP and either cardiac output or renal blood flow to characterize the temporal profile of systemic and renal hemodynamics, respectively in the DOCA-salt hypertensive rats. In Specific Aim 1, we will compare the effects of lesions of the CVOs, the area postrema (AP) and subfornical organ (SFO), and the chronic intracerebroventricular administration of a mineralocorticoid receptor (MR) antagonist and an antagonist of amiloride-sensitive sodium channels (benzamil) on these hemodynamic profiles and Fos immunoreactivity of key central regulatory sites. In Specific Aim 2, we will establish the effect of interruption of peripheral sympathetic pathways on the systemic and renal hemodynamic profiles using surgical and pharmacological methods, to determine the contribution of renal and "non-renal" sympathetic targets to the long-term regulation of MAP and the development of DOCA-salt hypertension. In Specific Aim 3, we will use a combination of frequency domain (i.e., power spectra and coherence analyses) and transfer function analyses on data collected in Specific Aims 1 and 2 to quantitatively determine the dynamic relative contributions of neurogenic and autoregulatory control of vascular tone in DOCA-salt hypertension. Taken together, this integrative physiological approach will advance our understanding of the neural mechanisms for long-term control of arterial pressure and pathogenesis of neurogenic hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPEPTIDES AND CARDIOVASCULAR REGULATION Principal Investigator & Institution: Brooks, Virginia L.; Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 31-MAR-2004 Summary: (Adapted from the application) Numerous studies suggest that increases in sodium chloride (NaCl) intake increase arterial pressure in several hypertensive models in part by activating the sympathetic nervous system. However, whether salt exerts a similar sympathoexcitatory action in normal conscious animals is unclear. Therefore, this proposal tests the general hypothesis that increased dietary NaCl does increase sympathetic activity, but this action is normally counterbalanced by direct and indirect (decreased angiotensin II-induced sympathoexcitation and baroreflex activation) effects of salt to decrease sympathetic activity. To test this general hypothesis, the following specific hypotheses will be examined. 1) Acute increases in NaCl increase sympathetic activity, but this effect is normally counterbalanced by decreases in circulating angiotensin II (AII) and baroreflex activation. 2) Chronic changes in NaCl intake are directly related to changes in sympathetic activity, vasopressin and activity of the hypothalamic-adrenal pituitary axis, but these actions are normally counterbalanced by reciprocal changes in AII. 3) Changes in dietary NaCl influence sympathetic activity in part by activation of osmoreceptors 4) Chronic increases in NaCl influence activity of sympathetic postganglionic neurons by altering expression of tyrosine hydroxylase and the norepinephrine transporter. 5) If the balance between the sympathoexcitatory and sympathoinhibitory effects of NaCl is disrupted, hypertension will be produced. These hypotheses will be tested in conscious rats by examining the acute and chronic effects of changes in NaCl intake, with and without fixing the activity of the renin-angiotensin
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Aldosterone
system, on renal and lumbar sympathetic activity, plasma catecholamines, vasopressin and corticosterone levels and ganglionic mRNA levels for tyrosine hydroxylase and the norepinephrine transporter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NH4+ TRANSPORT IN RENAL INNER MEDULLARY COLLECTING DUCT Principal Investigator & Institution: Wall, Susan M.; Professor; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2002 Summary: The collecting duct plays a major role in the excretion of total ammonia (NH3 and NH4 plus), the major regulatable component of urinary net acid excretion. Ammonium (NH4plus) secretion by the collecting duct is attributed to active proton secretion in parallel with the passive diffusion of NH3. However, our laboratory has demonstrated direct NH4plus transport in the terminal inner medullary collecting duct (tlMCD). We have shown that NH4plus and Kplus compete for a common binding site on the Naplus minus- ATPase and that inhibition of the Naplus pump decrease transepithelial net acid secretion through blockade o Na plus minus pump mediated NH 4 plus transport. Uptake of NH4 plus across the basolateral membrane of the tlMCD by the Naplus minusKplus - ATPase, provides a source of Hplus for luminal acidification and the titration of other luminal buffers. Unlike the m ore proximal collecting duct segments, in the tlMCD interstitial and luminal NH3 and NH4plus concentrations have been measured. Thus, transporter mediated NH4plus flux can be placed in context with known NH3 and NH4 plus gradients to determine the physiological role for Na plus pump-mediated NH 4 plus transport. However, it is not known if changes in Na plus pump activity in vivo regulate transepithelial net acid secretion. If net acid secretion across the apical membrane is increased following in vivo conditioning, it is expected that across the basolateral membrane net Hplus uptake or OH/HCO3 exit would increase in parallel. This project will determine if Na plus pump number and Na plus pump-mediated ion transport are regulated by aldosterone administration in vivo. We will then test if Na plus pump activity increases, in parallel, with both total and ouabain-sensitive NH4 plus uptake and transepithelial net acid secretion. Hence, we will establish if changes in NH4 plus uptake in vivo regulate net acid secretion. Aims of this proposal are to determine the following in the rat tlMCD: 1) If mineralocorticoid increases Na plus, K plus -ATPase-mediated ion transport and Na plus pump number. 2) If mineralocorticoid increases NH 4 plus uptake across the basolateral membrane. 3) If mineralocorticoid increases total and ouabain-sensitive net acid secretion and 4) If mineralocorticoid stimulates other basolateral H plus or OH/HCO3 transport pathways, providing a source of protons for apical secretion. The aims will be addressed using isotopes and immunoblots of tlMCD cells in suspension. Observations will be extended using tlMCD tubules perfused in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC OXIDE REGULATION OF ADRENAL STEROIDOGENESIS Principal Investigator & Institution: Campbell, William B.; Associate Professor; Pharmacology and Toxicology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005
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Summary: (provided by applicant): Vascular endothelial cells (ECs) release a number of biologically-active mediators (PGI2, nitric oxide (NO) and endothelin) that act on adjacent smooth muscle cells to influence vascular tone. In the adrenal cortex, as adrenal arteries get smaller and divide into capillaries and sinusoids, the smooth muscle layer is lost and the abluminal side of the EC comes in close anatomical contact with the steroidogenic cells. Thus, in the capillaries of the adrenal cortex, these mediators may influence the function of the adjacent steroidogenic cells. We have focused our studies on the role of endothelial-derived NO on steroidogenesis. We found that the NO donors inhibit angiotensin II (All)-stimulated aldosterone release. The inhibition by NO is not mediated by cyclic GMP but by NO binding to the cytochrome P450 enzymes involved in aldosterone biosynthesis. We were unable to detect NO synthesis, NO synthase (NOS) activity or NOS protein in ZG cells. However, adrenal capillary ECs contain NOS and release NO. We wilt test the hypothesis that ECs, which are in close anatomical proximity to ZG cells in the adrenal cortex, release NO and regulate or modulate aldosterone release. The proposed studies will investigate the effects of exogenous, endogenous and endothelial-derived NO on aldosterone release. These studies will be conducted in vitro in cultured bovine ZG cells and adrenal capillary ECs. Also, studies will be performed in the perfused rat adrenal gland and in vivo in anesthetized rats. The hypothesis will be tested by addressing four specific aims: (1) We will characterize the effect of exogenous NO on aldosterone release in cultured bovine ZG cells. The effect of the NO donor, deta-nonoate, will be tested on aldosterone release under conditions that vary the oxygen concentration. Additional studies will determine the biosynthetic step inhibited by NO and the effect of chronic NO treatment on aldosterone production and steroidogenic enzymes. (2) Since ZG cells do not have NOS, we will determine the effect of endogenous NO by conferring NOS activity on ZG cells by transducing the cells with an adenovirus containing NOS. (3) We will characterize the influence of endothelialderived NO on ZG cell aldosterone release. Using co-incubation of ECs and ZG cells, we will determine the effect of agonists on the release of NO from ECs and the action of this NO on ZG cell aldosterone release. (4) We will determine the role of endothelial NO in regulating steroidogenesis and adrenal blood flow in the in situ perfused adrenal gland and in vivo in anesthetized rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OBESITY, NITRIC OXIDE, OXIDATIVE STRESS, NA SENSITIVITY Principal Investigator & Institution: Flack, John M.; Professor; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: We propose a 39-week clinical study in healthy, normotensive, overweight (BMI equal to or more than 25 kg/m[2]) African American men and women aged 45 years and older that, after an initial screening and eligibility period (4 weeks), will be conducted in three phases. Phase 1 (9 weeks) begins the isocaloric 100 mmol dietary sodium diet phase. After the initial 3 weeks, a six-week period of 100 mmol/d sodium supplementation will be administered to determine salt sensitivity. Phase 2 (8 weeks) will maintain the 100 mmol sodium dietary intake and will additionally add a weight loss component to attain weight loss of about 1.5 - 2 pounds/week. Phase 3 (18 weeks) will consist of a two-period crossover trial consisting of randomization to the treatment sequence of dietary sodium supplementation of 100 mmol/d (6 weeks) followed by placebo (6 weeks) or vice versa. A 6-week placebo washout period will separate the two active periods. The 100 mmol sodium/weight loss diet from phase 2 will be maintained during this treatment phase. The difference in BP between the end of the sodium and
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Aldosterone
placebo periods will determine salt sensitivty after weight loss. The overarching study hypothesis is that obesity-related salt sensitivity is attributable, in large degree, to oxidative-stress mediated reductions in nitric oxide [NO] availability. The destruction of NO is linked to obesity-related elevations of non-esterified fatty acids, leptin, and reninangiotensin-aldosterone system activity - all of which are known to increase oxidative stress. Genetic variation in the angiotensin converting enzyme, specifically homozygosity for the insertion [I] polymorphism, will predict higher levels of salt sensitivity, oxidative stress, and lesser NO production. Environmental stressors interact with obesity to augment salt sensitivity. We further hypothesize that the degree of reversibility of salt sensitivity will closely parallel weight loss-induced reductions in oxidative stress. The primary specific aim of the study is to determine the main and interactive effects of stressors, obesity, and genetic variation of the ACE and endothelial nitric oxide synthase (eNOS) genotypes on oxidative stress and salt sensitivity and, after weight loss, to re-examine these effects as well as to link changes in oxidative stress to persistence of salt sensitivity between study phases 2 and 3. This study will provide important new insights into the pathophysiology of salt sensitivity in African Americans who are at high risk for development of hypertension and related cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE STRESS ATTENUATES NA+:CA+ EXCHANGER ACTIVITY Principal Investigator & Institution: Unlap, Menjor Tino.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 06-AUG-2001; Project End 31-JUL-2006 Summary: (Applicant?s abstract) The Na+:Ca2+ exchanger is a major regulator of intracellular calcium ([Ca2+]I) in renal contractile cells including afferent arteriole smooth muscle cells and mesangial cells. Dysregulation of [Ca2+]I in these contractile cells can lead to deleterious pathogenesis of salt sensitive hypertension through dysregulation of [Ca2+]I is oxidative stress, a condition characterized by excessive levels of reactive oxygen metabolites (ROM). The mechanism by which oxidative stress effects dysregulation of renal contractile cell [Ca2+]I in salt-sensitive hypertension is not known. However, studies have shown that under oxidative stress conditions, levels of the cells, is attenuated. This occurs, in part, through inaction of NO with the superoxide anion, O2, forming peroxynitrite (ONOO-). Peroxynitrite has been implicated in cancer, neurodegenerative diseases, and salt-sensitive hypertension. The formation of this product leads to nitration of tyrosine residues in a number of proteins and inactivation of these proteins, in part, through protein aggregation and degradation. Because of the critical role that the Na+-Ca2+ exchanger plays in regulating [Ca2+], in renal contractile cells, we propose and will test the hypothesis that dysregulation of [Ca2+}I under oxidative stress conditions occurs through attenuation of Na+:Ca2+ exchanger activity in these cells. We will examine the effects of oxidative stress on Na+-Ca2+ exchanger activity in primary cultures of mesangial cells of Salt Sensitive (S) and Salt Resistant Dahl/Rapp rats, a genetic model of hypertension that mimics this disorder in humans. We will also examine the effects of oxidative stress on exchanger activity in opossum proximal tubule (OK-PTH) cells which have been stably transfected with either the salt resistant (RNCX1) or the salt sensitive (SNCX1) Na+:Ca2+ exchanger isoform that we have recently cloned from mesangial cells of S and R rats. We will examine exchanger nitration, phosphorylation, and translocation under oxidative stress conditions and determine how they relate to the attenuation of exchanger activity.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADAPTATIONS
PERINATAL
HYPOXIA--ADRENOCORTICAL/METABOLIC
Principal Investigator & Institution: Raff, Hershel; Professor; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: (Adapted from investigator's abstract): This is a proposal to characterize the adrenocortical adaptation to hypoxia in the perinatal period. In specific aims 1-3, the adaptation to and recovery from pre- and postnatal hypoxia in the neonatal and juvenile rat will be studied by measuring plasma hormone concentrations and electrolytes, aldosteroidogenesis in vitro, the expression of steroidogenic enzyme mRNA's, and mitochondrial histomorphometry. Specific aim 4 will determine if increased ACTH is a major mechanism in the adaptation of the aldosteroidogenic pathway to hypoxia in the neonatal rat. Specific aim 5 will determine if the dramatic changes in plasma lipids which occur in the hypoxic, suckling rat, are a major influence on aldosteroidogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS NETWORK Principal Investigator & Institution: Chapman, Arlene B.; Professor of Medicine; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): We seek to be a participating clinical center (PCC) in the RFA entitled "Polycystic Kidney Disease Clinical Trials Network." Hypertension is common, occurs early, and is associated with a faster progression to renal failure in ADPKD. We have shown activation of the systemic renin-angiotensin-aldosterone system (RAAS) in hypertension associated with ADPKD prior to loss of renal function, and that intrarenal activation of RAAS is present. We have demonstrated that angiotensin converting enzyme inhibition alone (ACEI) has beneficial effects by reducing proteinuria and regression of left ventricular hypertrophy as well as improving effective renal plasma flow, and this may relate to filtration fraction. In contrast to other kidney diseases, ACEI has not been as successful in preventing loss of renal function. This may relate to study design issues, sample size, inclusion of low risk individuals not progressing, and less than maximal blockade of RAAS. Therefore, we propose to assess the effect of combination therapy, i.e. ACEI, angiotensin receptor blockade (ARB), and aldosterone antagonism (spironolactone) in the setting of rigorous blood pressure control (<125/75 mm Hg) on the rate of loss of renal function in ADPKD while controlling for other potential contributors to loss of renal function. ADPKD children with hypertension demonstrate a greater increase in renal volume than other ADPKD children in the setting of normal renal function. Using MRI, we have shown decreased renal blood flow in ADPKD as compared to age and gender-matched children suggesting that activation of RAAS occurs early in ADPKD children. We propose to study a special population of ADPKD subjects (children) throughout adolescence to determine the safety and efficacy of ACE/ARB combination therapy in the acute and chronic setting on renal blood flow, and the rate of renal cyst and total renal growth. Taken together, these studies will determine if maximal inhibition of RAAS prevents loss of renal function in ADPKD adults and if combination ACEI/ARB therapy maintains renal blood flow while slowing renal and cyst growth in ADPKD children. Ultimately these studies should demonstrate slowing or halting progression of ADPKD.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS NETWORK Principal Investigator & Institution: Perrone, Ronald D.; Associate Professor; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) is the most common lethal monogenetic disease, affecting 1/500 to 1/1000 of the US population. 50% of those affected with ADPKD will develop end-stage renal disease by the 6th decade of life. There are no proven therapies to slow the inexorable loss of kidney function in those with progressive disease. Interruption of the reninangiotensin-aldosterone system (RAAS) has been shown to reduce the progressive decline in renal function in both diabetic and non-diabetic kidney diseases, but it is unknown whether these results extend to ADPKD. Abundant evidence implicates angiotensin II in the pathogenesis of hypertension, but small single-center studies of limited duration have reported inconsistent results of ACE inhibitor (ACE-I) therapy on disease progression. This application is submitted in response to RFA DK-01-029 to establish a PKD Clinical Trials Network of clinical centers that will each enroll 500 ADPKD patients and conduct a clinical trial to assess the efficacy of therapeutic interruption of the RAAS on renal progression. We have proposed a randomized, double-blinded trial to compare ACE-I vs. active control in hypertensive ADPKD patients with renal insufficiency (GFR 30-65 ml/min/1.73 m2) on the time to reach a composite outcome of doubling of serum creatinine, ESRD, or death. The Clinical Center will be based at the New England Medical Center and Beth Israel Deaconess Medical Center. The Principal and Co-Principal Investigators have had career-long interests in ADPKD and personally care for large numbers of ADPKD patients. We have identified 107 potentially eligible patients within our clinical sites. Additional strategies will be used to target patients locally and within contiguous New England States. Strong institutional support is available at the highest levels, including the General Clinical Research Centers at NEMC and BIDMC. As part of this RFA, we have proposed a pilot study to assess the safety of cyclooxygenase-2 inhibition, which has been implicated in angiogenesis and cyst development in animal models of ADPKD. Thirty ADPKD patients with GFR >70 ml/min/1.73 m2 will be randomized to treatment with celecoxib vs. placebo and followed for 16 weeks. Change in GFR is the primary outcome measure and incidence of hyperkalemia, fluid retention, and elevated blood pressure will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF ANGIOTENSIN PEPTIDE RECEPTORS Principal Investigator & Institution: Diz, Debra I.; Professor; Wake Forest University 1834 Wake Forest Road Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Ang-(1-7) activates the vasodilator systems which oppose the hypertensive At1-mediated actions of Ang II. We propose three aims to investigate the potential mechanisms for the actions of Ang-(1-7). Aim 1: A novel non-At1, non-AT2 receptor [AT(1-7)] is responsible for the hemodynamic and vascular actions of Ang-(1-7). 125I[Sar/1-Thr/8]Ang II binding, in the presence of blocking concentrations of AT1 and AT2 receptor antagonists, demonstrated a novel Ang-(1-7) receptive site sit mesenteric artery and aorta of SHR treated with a combination of lisinopril/losartan. The binding site
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displayed a pharmacological profile with agonists and antagonists that previously characterized in endothelial cells. We will now determine whether this receptor is unique to the vasculature or exhibits a more widespread distribution (kidney, heart and brain) using receptor binding techniques. Aim 2: Ang-(1-7) actions blocked by At1 or AT2 receptor antagonists are not attributable to classical AT1 or AT2 receptors. In addition to the actions of Ang-(1- 7) at the novel non-AT1 non-AT2 AT(1-7) receptor, several actions of Ang-(1-7) are similar to Ang II or are blocked by AT1 or AT2 receptor antagonists. Ang-(1-7) generally displays low affinity for typical AT1 or AT2 receptors and is not associated with vasoconstrictor, pressor or drinking responses. Thus, we propose that isoforms of AT1 or AT2 receptors are responsible for the actions of Ang-(17) that are blocked by AT1 or AT2 receptor antagonists. We will use receptor knockout mice to show that the Ang-(1-7) actions or binding sites inhibited by AT1 or AT2 receptor antagonists do not persist in these receptor knockout animals. We will also characterize the protein forms of At1 and AT2 receptors known to exist in various tissues for differences in pharmacology toward Ang-(1-7) and [D-Ala/7]-Ang-(1-7). Aim 3: Ang-(1-7) counteracts the actions of Ang II at the AT1 receptor by desensitization and/or down-regulation of the AT1 receptor via homologous (through prostaglandins or nitric oxide) mechanisms. Acute and chronic exposure to elevated Ang-(1-7) decreases AT1 receptors and AT1 receptor-mediated responses in brain, kidney and cells in cultured. Prostaglandins causes heterologous down-regulation of other receptors and decrease in AT1 receptor mRNA with nitric oxide are reported. Alternatively, Ang(1-7) acts as a weak agonist at the AT1 receptor, in a process similar to homologous receptor regulation. Preliminary studies in CHO-AT/1A cells indicated a direct effect of Ang-(1-7) on the AT/1A receptor, consistent with agonist-induced homologous downregulation. We will use in vivo and in vitro models to determine the effects of acute and long-term treatments with Ang-(1-7) on AT1 receptor affinity and density and AT1 receptor mRNA by RT-PCR in the presence or absence of cyclooxygenase or nitric oxide synthase blockade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF KALLIKREIN MK9 IN HYPERTENSION Principal Investigator & Institution: Uddin, Mukarram; Anatomy and Physiology; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (Adapted from applicant's abstract): This seeks funding to retrain, to acquire additional technical skills, and to gain hand-on experience on the state-of-the-art molecular biology techniques. This retraining, and acquirement of additional state- ofthe-art technical skills will help the candidate not only in gaining cutting-edge technology experience but also making him competitive in seeking R01 type funding. The experience gained by the candidate will be applied to the proposed investigation in the evaluation of altered gene regulation of epidermal growth factor- binding protein (EGF-BP C), (Kallikrein mK9),a prorenin converting enzyme in mice genetically selected for high blood pressure. The funding will also provide opportunity to train minority students in the area related to cardiovascular diseases. Preliminary results of the proposed investigation, utilizing the submandibular gland(whole issue) from mice genetically selected for high blood pressure, indicated increase expression of EGF-BP C(kallikrein mK9), a prorenin converting enzyme. Immuno- histochemical localization of this kallikrein indicated it to be present in the submandibular gland duct cells. It is hypothesized that higher expression of this prorenin converting enzyme is due to altered activity of its gene MKlk-9. The main objective of the proposed investigation is to
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evaluate the molecular mechanism of the up regulation of EGF-BP C in long-term duct cell cultures. Specific aims to test the hypothesis include development of long- term duct cell cultures, quantitation and steady state levels of EFG-BP specific mRNA, mutational changes in the promoter region of EGF-BP C gene (mKlk-9), and evaluation of transcription factor binding to the promoter region of this kallikrein. This research will be conducted in the mentor's laboratory, Department of Biochemistry, Vanderbilt University and the candidate's laboratory, Department of Anatomy and Physiology, Meharry Medical College. Both of these laboratories are located in Nashville, TN. During retraining, facility will be developed with techniques, data collected and affiliation developed will further the missions of Meharry Medical College. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SODIUM IN TIGHT EPITHELIA Principal Investigator & Institution: Eaton, Douglas C.; Professor and Deputy Chairman of Physiol; Physiology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-AUG-1987; Project End 31-JUL-2007 Summary: The long term goal of this program is to examine the control and regulation of ion transport in epithelial tissue. In particular this project will use single channel and biochemical methods to examine the regulation of amiloride-blockade sodium channels in renal and lung epithelial cells. These channels are interesting because of their relative uniqueness among channels in transporting tissue and because of the interesting hormonal regulation of these channels. However, the mechanisms for regulation of these channels have not been completely described. Therefore, this project will further investigate the signaling cascades which regulate sodium channels in three sodiumtransporting epithelial cell lines using patch clamp techniques supplemented by direct biochemical measurements. The specific aims for the proposed grant period will investigate four signaling cascades that regulate sodium transport. The aims are (1) further examine the regulation of sodium channels by heterotrimeric G protein signaling cascades; specifically, what is the nature of the interaction between Galpha-3 and ENAC; do the G protein alpha subunits activate Na channels directly or do they activate some other effector molecule closely associated with the inner surface of the apical membrane; and do G protein betagamma subunits alter ENaC activity? (2) Examine the regulation of sodium channels by small G protein signaling cascades. The activation of one small G protein, K-Ras2A, is required to sustain normal ENaC activity. Elements of the K-Ras signaling cascade appear to be closely associated with the cytosolic surface of the apical membrane since the cascade can be activated in excised, inside-out patches. Therefore, the mechanism of activation of K-Ras and the signaling molecules activated by K-Ras will be examined. 3) Examine the regulation of sodium channels by inositol lipids and inositol lipid kinases. Sodium channels in excised, inside-out patches require the presence of phosphatidylinositol-4,5-bis-phosphate (4,5-PIP/2) and A6 cells have the necessary enzymes to produce 4,5- pip/2. (4) Investigate the mechanisms by which aldosterone increases sodium channel activity. Demonstrate that the signaling cascade that begins with aldosterone activation of K-Ras and leads to the PI-3K- mediated production of 3,4,5-PIP3 involves activation of phosphatidylinositol-dependent kinase (PDK1/2), serum glucocorticoid- dependent kinase (SGK), and the ubiquitin ligase, Nedd4. Determine that these signaling molecules are activated by activation of PI-3kinase and that 4-PIP-5-kinase is activated to produce 4,5-PIOP2 and subsequently 3,4,5PIP/3. Finally, we will use commercially available gene chips to identify new aldosterone-induced genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF THICK ASCENDING LIMB ACID-BASE TRANSPORT Principal Investigator & Institution: Good, David W.; Associate Professor; Otolaryngology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-JUL-1987; Project End 31-MAY-2008 Summary: (provided by applicant): The renal thick ascending limb contributes to the maintenance of acid-base homeostasis by reabsorbing both bicarbonate and ammonium. Our long-term goal is to understand the cellular, biochemical, and molecular mechanisms by which these transport processes are regulated. The central hypothesis of this proposal is that the control of HCO3 absorption in the medullary thick ascending limb (MTAL) depends on the regulation of both apical and basolateral Na+/H+ exchangers. We have developed evidence of a novel mechanism for regulation of HCO3 absorption in the MTAL, in which the activity of the apical Na+/H+ exchanger, which is directly involved in HCO3 absorption, is regulated by the activity of the basolateral Na+/H+exchanger. The current studies are directed toward understanding the mechanism whereby basolateral Na+/H+ exchange regulates apical Na+/H+ exchange, and identifying physiological factors and signaling pathways that regulate cross-talk between the exchangers. Preliminary studies show that the cross-talk mechanism is genetically eliminated in MTAL from NHE1 knockout mice, which will be studied to define the role of basolateral Na+/H+ exchange in regulating apical Na+/H+exchange and HCO3 absorption. The Specific Aims include: 1) determine the role of the actin cytoskeleton in mediating regulation of the apical Na+/H+ exchanger by the basolateral Na+/H+ exchanger, 2) examine chronic regulation of the interaction between basolateral and apical Na+/H + exchangers by changes in dietary Na+ intake, and 3) examine acute regulation of cross-talk between the exchangers by growth factors and aldosterone via extracellular signal-regulated kinase- and phosphatidylinositol 3kinase-dependent pathways. Biochemical analyses and fluorescence microscopy will be integrated with ion transport measurements in MTALs microdissected from rats and gene-targeted mice to provide a detailed understanding of the cross-talk mechanism and its role in HCO3 absorption. These studies will identify novel mechanisms for the regulation of Na+/H + exchange activity and acid secretion in renal tubules and will investigate a new biological process involving cross-talk between Na+/H+ exchangers in basolateral and apical membranes of epithelial cells. The results will enhance our understanding of the role of the MTAL in the physiological and pathophysiological control of acid-base balance. In addition, they will be the first to identify a function for NHE1 in transepithelial transport in the kidney and to define a role for this basolateral exchanger in the acute and chronic regulation of HCO3 absorption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATORY MECHANISMS OF ALDOSTERONE SECRETION Principal Investigator & Institution: Bollag, Wendy B.; Associate Professor; Medicine; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2003; Project Start 04-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Angiotensin II (AngII) and elevated extracellular K+ levels [(K+) e] are the primary physiologic regulators of the synthesis and secretion of aldosterone, the hormone responsible for maintaining normal salt balance in the body. Previous studies have indicated that elevated (K+)e stimulates steroidogenesis by depolarizing the glomerulosa cell, thereby activating voltage-dependent Ca2+ channels
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and increasing Ca2+ influx. This enhanced influx, in turn, activates Ca2+-dependent processes, such as Ca2+/calmodulin-dependent protein kinases. In novel findings we have recently shown that elevated (K+) e also activates phospholipase D (PLD) and increases the phosphorylation of an endogenous protein kinase C (PKC) substrate (myristoylated alanine-rich C kinase substrate or MARCKS). PLD-mediated hydrolysis of membrane phosphatidylcholine generates phosphatidic acid, which can be dephosphorylated to produce diacylglycerol, the natural activator of PKC. Thus, we propose that the elevated (K+)e-induced increase in Ca2+ influx activates PLD to stimulate PKC activity, thereby eliciting MARCKS phosphorylation and sustained aldosterone secretion. Our data also suggest an involvement of PLD in the process of priming. Priming refers to the ability of a pretreatment with AngII to sensitize glomerulosa cells to respond to agents that stimulate Ca2+ influx, including small elevations in (K+) e, with enhanced aldosterone secretion relative to "naive" unpretreated cells. We have postulated that priming is the result of the observed persistent elevation in PLD-generated diacylglycerol retaining PKC at the plasma membrane, a site at which the enzyme is poised to activate in response to increased Ca2+ influx. Using two-dimensional polyacrylamide gel electrophoretic analysis, proteomics and mass spectrometric identification of phosphorylation sites, PLD activity measurements, overexpression of PLD isoforms, aldosterone radioimmunoassays and western blot analysis, we wish to test the hypothesis that a PLD-generated signal retains PKC at the plasma membrane to result in the induction of priming. We will also define the mechanism of elevated (K+)e-induced PLD activation and examine the hypothesis that this activation stimulates PKC activity, MARCKS phosphorylation and aldosterone secretion. Since priming would allow enhanced aldosterone secretion to multiple AngII or sequential AngII and elevated (K+)e exposures, this research may provide novel insights into normal and pathological changes in steroidogenesis under conditions of altered sodium intake. The complex interactions between AngII and serum K+ levels suggest that abnormalities in the glomerulosa cell response to either agonist, or both, may contribute to the development of some forms of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RENAL SODIUM TRANSPORT IN THE OBESE ZUCKER RAT Principal Investigator & Institution: Ecelbarger, Carolyn A.; Professor; Medicine; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Obesity and insulin resistance are associated with hypertension. Inappropriate retention of sodium by the kidney is likely to play a major role. We previously showed that the obese Zucker rat (a model for these disorders) have increased renal protein abundance for three major sodium transport proteins: the alpha1 subunit of Na-K-ATPase, the thiazide-sensitive NaCI cotransporter (NCC or TSC) and the beta-subunit of the epithelial sodium channel (ENaC). In contrast, as, they aged, obese rats developed renal hypertrophy along with diabetes and had a relative decrease in many important salt and water transport proteins, as compared to age-matched controls. We suggest that dysregulation of several important hormone systems in sodium balance may play a role in both alterations in sodium transport protein expression, as well as, the rapid develop of nephropathy. Candidate systems include the renin-angiotensin-aldosterone system (RAAS) and insulin (and or insulin resistance). We hypothesize that dysregulation of major sodium transport proteins of the kidney in the obese Zucker rat with age, is due at least in part to increased RAAS activity, and hyperinsulinemia, which in combination, result in inappropriate sodium retention and
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elevated blood pressure. Our specific aims include: 1) to determine if angiotensin II At1a receptor expression, binding, and activity is upregulated in the obese Zucker rat and whether this upregulation plays a role in changes in renal sodium transporter regulation, blood pressure, and renal hypertrophy; 2) to determine if enhanced mineralocorticoid receptor (MR) activity plays a role in increased whole kidney protein abundance of the thiazide-sensitive NaCI cotransporter (NCC), blood pressure, and renal hypertrophy, in the obese Zucker rat; 3) to determine the cellular location and sensitivity of the renal insulin receptor in obese Zucker rats relative to lean age-mates; 4) to determine whether treatment of insulin resistance with a PPAR-gamma agonist will decrease relative renal protein abundance of NCC, beta-ENaC, and Na-K-ATPase, as well as reduce blood pressure and renal hypertrophy in the obese Zucker rat, and whether these effects are reversed with short-term insulin infusion. These studies will allow us to determine the importance of each of these potential regulatory hormone systems in dyregulation of sodium transporter expression, sodium balance, and blood pressure in these obese rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF SENSING OF K+ INTAKE IN K+ HOMEOSTASIS Principal Investigator & Institution: Youn, Jang H.; Associate Professor of Physiology and Bi; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Extracellular (ECF) K+ homeostasis is critical for normal cardiovascular and neuromuscular functions and is maintained by renal and extrarenal mechanisms. We recently developed the K clamp technique, which can quantify both renal K+ excretion and extrarenal cellular K+ uptake in vivo. Using this technique, we demonstrated that both renal K+ excretion and extrarenal cellular K+ uptake are rapidly and profoundly suppressed during K+ deprivation. These changes for ECF K+ conservation have been traditionally explained to arise from decreased ECF K+ levels and/or consequent decrease in aldosterone secretion. However, we found that this triggering of ECF K+ conservation can occur in rats in the absence of changes in plasma [K +] or [aldosterone] when K+ intake is reduced to 1/3 of control. The objective of this project is to test the hypothesis that K+ intake is sensed by K+ sensors in the portal vein, and both renal K+ excretion and extrarenal cellular K+ uptake are regulated by this signal. To achieve this goal, we will collaborate with Dr. Casey Donovan at our institution and employ strategies similar to those used to demonstrate the presence of portal vein glucose sensors in rats, i.e., "local irrigation" and portal denervation techniques. Our preliminary data showed that reducing K+ intake to 1/3 of normal for only one night (12 h) was sufficient to trigger marked renal K+ conservation. In the proposed studies we will use this overnight low K+ feeding model to address the following specific aims. Aim 1. Test for the existence of portal (or splanchnic) sensing of Kv intake and its regulation of renal and extrarenal K+ handling. We will test whether the triggering of ECF K+ conservation by overnight low dietary K+ intake is prevented by parallel K+ supplementation via intragastric or intraportal infusion, which would be sensed by the hypothetical portal vein (or splanchnic) sensors, but not by K+ supplementation via systemic infusion. Aim 2. Test for a role of portal sensing of K+ intake in extracellular K+ homeostasis. We propose to test whether portal denervation ablates portal sensing of Kv intake and, if so, whether it impairs the acute and chronic regulation of ECF K+ homeostasis by delaying renal and extrarenal responses to altered
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K+ intake. Significance: This project will potentially identify an important, previously unknown regulator of ECF K+ homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SALT AND WATER TRANSPORTER EXPRESSION IN AGING KIDNEYS Principal Investigator & Institution: Terris, James M.; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: With aging there is a progressive loss of renal concentrating ability. Acute illness in geriatric patients is often complicated by derangements in fluid and electrolyte balance that are costly, inconvenient and often delay recovery and prolong hospitalization. The long-term goal of this proposal is to better understand the process of salt and water balance in the intact aging kidney. Four water channels (aquaporins; AQP-1 to 4), four urea transporter isoforms (UT-A1 to 4), and several major sodium transporter proteins have been characterized in the nephron and vasa recta that are critical for renal regulation of salt and water balance and the urinary concentrating process. It is generally accepted that a decrease in the abundance of the vasopressin regulated water channel, AQP-2, contributes to diuresis seen with aging. The central hypotheses to be tested in these studies is that a decreased reabsorption of sodium, urea and water, independent of vasopressin and AQP-2 abundance, also contribute to this water loss. Our rationale is that an examination of the expression levels, intracellular distribution and regulation of these proteins with age will provide additional molecular understanding of the physiology and pathophysiology of this condition and lead to improvements in health care of the aged. To test this hypothesis we propose the following 2 Specific Aims: 1) Determine the abundance and intracellular distribution of proximal tubule and descending thin limb aquaporins-1, collecting dust aquaporins-2, -3 and -4, the four known medullary UT-A area isoforms and the major sodium channels among the nephron in young (3 month), middle aged (12 months) and elderly (24 months) F344XBNFI rats, a National Institute of Aging (NIA) endorsed model for renal aging studies. 2) Correlate plasma levels of vasopressin (ADH) and aldosterone with differences in transporter and channel protein abundance and intracellular in young, middle-aged and elderly F344xBNF1 (F344BN) rats. These studies are important because they will identify target transporters and hormonal relationships for future in-depth mechanistic investigations of this major disorder of the aged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TOXICITY
STEROID
AS
CYTOPROTECTANTS
AGAINST
OXIDATIVE
Principal Investigator & Institution: Chen, Qin M.; Associate Professor; Pharmacology and Toxicology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Stress is known to cause an increase in the synthesis of corticosteroids by the adrenal glands. Although corticosteroids have been shown to contribute to the pathophysiology of suppressed Immune response and a number of psychiatric disorders, the effect of CT on the heart remains unclear. Doxorubicin (Dox) is an anti-neoplastic drug that can produce chronic cardiac toxicity which is manifested as dilated cardiomyopathy. An important feature of this form of cardiomyopathy is the apoptosis of cardiomyocytes. Our preliminary studies found that corticosterone (CT)
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pretreatment prevented Dox from inducing apoptosis of cardiomyocytes. The glucocorticoid receptor antagonist mifepristone prevented CT from inducing a cell survival response. Several forms of g!ucocorticoids, aldosterone, progesterone and retinoic acid but not estrogen, testosterone or L-thyroxin can inhibit apoptosis of cardiomyocytes. Analyses of ERK, Akt and SGK-1 activities or bcl-2 expression indicated that CT neither activated the known survival kinases nor elevated the expression of the anti-apoptotic gene bcl- 2. The conditioned medium of CT-treated cardiomyocytes shows partially cytoprotective effective. The TranSignal array approach found that CT treatment could potentially activate 21 transcription factors. We hypothesize that activation of the glucocorticoid receptor initiates transcriptional activation of survival genes in cardiomyocytes in vitro and in vivo. Specific aims of this grant include: 1) To test if CT binding causes its receptor to interact with and to activate multiple transcription factors in cardiomyocytes; 2) To test that the activation of cell survival genes contributes to CT-induced cytoprotection; and 3) To demonstrate that CT protects the heart from cardiomyopathy induced by Dox in vivo via inducing the transcription of cell survival genes. This project will combine our expertise in genomics, transcriptomics and proteomics to systematically study the linkage between the glucocorticoid receptor and cell survival mechanisms. Given the fact that stress is unavoidable in our daily life, this project will provide novel information to advance our understanding in the biological effect of corticosteroids on the heart. More importantly, since apoptosis has been shown to contribute to heart failure induced by the chemotherapy agent Dox as well as by many forms of cardiovascular disease, our finding and proposed mechanistic study will provide a hope for novel therapy against heart failure in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRODUCTION
STEROIDS
/VASCULAR
REACTIVITY
/NITRIC
OXIDE
Principal Investigator & Institution: Keller-Wood, Maureen E.; Professor and Chair; Pharmacodynamics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 06-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from applicant's description): The overall goal of these studies is to test the hypothesis that there is an interaction between increased secretion of adrenal corticosteroids and increased secretion of estrogen during pregnancy which is necessary for normal blood pressure control in the peripartal period. Studies in pregnant, hypocorticoid ewes and clinical experience in pregnant women with hypoadrenocorticism suggest that normal blood pressure control in late pregnancy requires increased adrenal secretion. Insufficient supply of cortisol results in rapid and profound hypotension, with increased morbidity and mortality in both mother and fetus. The experiments in this proposal will directly test the hypothesis that a decrease in cortisol at a time of increased estrogen results in a greater decrease in vascular reactivity to phenylephrine and that this correlates with increased production of nitric oxide production in one or more sites in the body. Four groups of ewes will be studied: adrenalectomized, ovariectomized ewes, adrenalectomized ovariectomized ewes treated with estradiol, adrenal- intact ovariectomized ewes, and adrenal-intact ovariectomized ewes treated with estradiol. All adrenalectomized ewes will be treated with aldosterone and cortisol for one week following surgery, and then the adrenal steroid infusions will be stopped to produce the hypoadrenal state. Animals will be studied at a time point (8 hours) in which the adrenalectomized estrogen treated animals are hypotensive, but the adrenalectomized ewes without estradiol treatment are not overtly hypotensive.
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Experiments will test vascular reactivity in response to phenylephrine in all 4 groups of ewes to test the hypothesis that estrogen administration decreases vascular reactivity in adrenalectomized ewes. Experiments will also determine plasma levels of nitrates and nitrites and the ability of infusion of L-NAME, an inhibitor of nitric oxide synthase (NOS), to increase vascular reactivity in adrenalectomized ewes with estradiol treatment. Experiments will also test the concentrations of cGMP, and levels of iNOS, eNOS, and nNOS protein measured by Western analysis and mRNA by RT-PCR in aorta, uterine artery, mesenteric artery, renal artery, renal interlobular artery, renal medulla and cortex, and skeletal muscle, taken from animals in the same 4 experimental groups. These experiments will determine if absence of cortisol results in increased NOS in one or more of these sites. Samples of tissue will also be examined by immunohistochemistry to more precisely identify the cell populations containing iNOS, eNOS or nNOS in these ewes. These experiments will therefore describe which isoform(s), and in which cells, NOS is altered by cortisol withdrawal, either alone or in combination with increased estrogen. This information will form the basis of future experiments to determine the mechanism of the interaction of estrogen and cortisol in control of NO and regulation of blood pressure during pregnancy. These studies will therefore add to our understanding of normal blood pressure control during pregnancy, and of the pathophysiology of hypoadrenocorticism at term. These studies will also to our understanding of the counterbalancing effects of increased cortisol and increased estrogens in control of normal blood pressure in normal pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND REGULATION OF EPITHELIAL SODIUM CHANNELS Principal Investigator & Institution: Canessa, Cecilia M.; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: The amiloride-sensitive epithelial sodium channel (ENaC) plays a central role in the maintenance of sodium homeostasis, it constitutes the main pathway for reabsorption of sodium in tight epithelia such as the distal nephron. The importance of the sodium channel in the maintenance of extracellular volume and blood pressure is underscored by the finding of mutations in the human genes that either active channels leading to hypertension (Liddle's syndrome), or conversely, decrease activity of channels leading to salt-wasting and hypovolemic states (pseudohypoaldosteronism). Elucidation of the mechanisms that normally regulate the function and expression of ENaC is of major importance for the understanding of blood volume maintenance in physiological and pathological conditions. The long term objectives of this work are to understand the molecular mechanisms of channel function and regulation. The specific goals of this proposal are: 1) to identify functional domains using the differences in properties exhibited by channels formed by ab and ag subunits. Mapping of functional domains will be performed using chimeras generated between the b and g subunits; 2) to elucidate the mechanics by which aldosterone mediates phosphorylation of ENaC. Aldosterone increase sodium permeability by increasing the abundance of sodium channels and by activating pre-existing channels. However, the mechanism(s) that mediate the activation of channels is still unknown. We propose that aldosterone induced phosphorylation is one of the mechanisms that activates pre-existing channels; 3) to understand the regulation of expression of ENaC by ubiquitination. We will examine the hypothesis that ubiquitination participates in endocytosis at the plasma membrane and in degradation of channels in intracellular compartments. Injected
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Xenopus oocytes and transfected cells will provide the expression systems for wild-type and mutant channels in which we will examine the functional properties, levels of expression, cellular distribution and rates of biosynthesis and degradation of channels. Experiments are designed to examine the activity and properties of channels by electrophysiologycal techniques. Ensembles of channels will be studied using the two micro-electrode voltage clamp and single channels using the patch-clamp technique. Biochemical, immunological, and molecular biological approaches will be applied to examine the state of phosphorylation and ubiquitination of the channel. These studies will identify important functional domains in the sodium channel, and are the first to explore two novel regulatory mechanisms of the function and expression of sodium channels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYSTEMIC BRADYKININ IN HUMAN HYPERTENSION Principal Investigator & Institution: Murphey, Laine J.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: The candidate, Dr. Laine Murphey, is a board certified internist and a pharmacologist experienced in studies of cardiovascular physiology. He seeks to continue to progress to independence as a patient-oriented researcher in the field of hypertension through a mentored career development plan that includes bedside research, laboratory studies and a focused curriculum in biostatistics, genetics and study design. The program will take place at Vanderbilt University, which has an historic and strong commitment to the mentored training of clinical researchers. The General Clinical Research Center at Vanderbilt provides the ideal environment for the proposed human studies. Research: Bradykinin, a cardioprotective peptide hormone, is a vasodilator and a natriuretic. In humans, bradykinin contributes to the acute hemodynamic effects of ACE inhibitors, a widely used class of drugs. Studies suggest that endogenous bradykinin may be decreased in human hypertension and that it is modulated by saltstatus, ethnic and genetic factors. To date, human studies of systemic bradykinin have been confounded by difficulties in measuring this rapidly metabolized peptide. Prior assays have relied on non-specific radioimmunoassay techniques. Recently, we studied the human in vivo metabolism of systemic bradykinin and identified BK1 -5 as the major stable plasma metabolite of bradykinin. To accurately measure bradykinin and BK1-5, we have developed highly specific and sensitive liquid chromatography-mass spectroscopy assays for these two peptides. Together, these advances in the field now provide powerful methods to determine the role of systemic bradykinin in cardiovascular homeostasis. In this application, I propose to use these new tools to test directly the hypothesis that systemic bradykinin is decreased in hypertension and that it is modulated by genetic, ethnic and environmental factors. The implementation of these studies in a mentored environment, together with participation in directed course work, will provide the applicant with the tools to become an independent patient-oriented researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: THE ANGIOTENSINOGEN GENE AND HUMAN HYPERTENSION Principal Investigator & Institution: Jorde, Lynn B.; Professor; Human Genetics; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 27-JAN-2003; Project End 31-DEC-2006
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Summary: (provided by applicant): Essential hypertension affects at least 25 percent of American adults, and it is a primary risk factor for heart failure, stroke, and kidney disease. Many, but not all, studies have shown that variants of the angiotensinogen gene (AGT) affect the risk of hypertension, but association studies conducted to date have been compromised by genetic heterogeneity and by the inherent complexity of hypertension as a phenotype. To overcome these difficulties, we will sequence or genotype a 14.4 kb region including AGT in more than 1,600 individuals sampled from populations throughout the world. This will permit us to explore fully the extent of allelic heterogeneity, haplotype variation, and potential for population stratification in the AGT gene. Approximately 600 of these individuals are clinically uncharacterized and will represent a broad range of worldwide human variation. Another 500 subjects are members of 40 Utah pedigrees that are part of the CEPH collection. These unique families have been heavily characterized genetically, and they are now being phenotyped for variables that include anthropometrics, blood chemistries, blood pressure measures, and plasma and urinary angiotensinogen. We will address the issue of genetic heterogeneity by testing associations between multi-SNP AGT haplotypes, angiotensinogen levels, and blood pressure. In addition, linkage disequilibrium patterns will be assessed to determine the density and nature of SNPs best suited for localizing a gene underlying a complex trait. We will address the issue of phenotypic heterogeneity in hypertension by performing extensive SNP typing on a set of 400 hypertensives and 100 normotensives collected by Dr. Gordon Williams. These clinically well-characterized subjects have been tested for their response to infused angiotensin-II under high and low sodium intake. This direct probe provides a hypertension endophenotype that is closer to the function of the AGT gene, yielding a more realistic and informative assessment of the relationship between AGT haplotype variation and hypertension risk. A phylogenetic analysis of AGT sequence variation in our worldwide sample will help to assess population stratification in association studies. In addition, this sample will allow us to test the hypothesis that the ancestral T235 AGT allele provided a selective advantage in the sodium-poor environment of sub-Saharan Africa. The results of this analysis may help to explain why African-Americans have elevated rates of hypertension. In summary, our extensive analysis of AGT variation in more than 1,600 subjects will clarify the role of this gene in essential hypertension and will test specific hypotheses about the evolution of AGT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE DASH-SODIUM TRIAL: GENETIC DETERMINANTS OF RESPONSE Principal Investigator & Institution: Svetkey, Laura P.; Assistant Professor; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-FEB-1997; Project End 31-MAR-2005 Summary: Essential hypertension results from the interaction of several genetic and environmental factors, including nutritional factors. The purpose of this study is to identify genes that modulate BP response to nutritional interventions. This proposal is being submitted as an amended continuation of the Dietary Patterns, Sodium Intake, and Blood Pressure study, hereafter referred to as the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial. The main trial is completed, and the phenotypes of interest (BP response to DASH diet and to reduced sodium intake) have been precisely determined using multiple, standardized blood pressure measurements. Dietary intake has been manipulated in a controlled feeding study. This proposal seeks to maximize the value of the DASH-Sodium trial by using existing high-quality data for a genetic
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association study. The hypothesis to be tested is that genetic makeup modulates the BP effects of DASH diet and reduced sodium intake through one or more of the following mechanisms: 1) effects on vascular tone; 2) effects on mineralocorticoid regulation of sodium homeostasis; and 3) effects on non-classical regulation of sodium homeostasis. Each potential mechanism is associated with a group of candidate genes: 1) angiotensinogen, angiotensin converting enzyme, angiotensin II receptor type 1, renin, and nitric oxide synthase; 2) aldosterone synthase, mineralocorticoid receptor, and 11beta hydroxysteroid dehydrogenase type II; and 3) beta2-adrenergic receptor, adducin, guanine nucleotide binding protein, and kallikrein. Each individual will be genotyped for 4-6 SNPs in each of these candidate genes, and tests for association will be performed. Biochemical markers will also be used to define intermediate phenotypes in exploratory analyses. The use of state-of-the-art genetic techniques in this uniquelycharacterized population will potentially increase our understanding of the mechanism(s) by which DASH diet and reduced sodium intake lower BP. Ultimately, increased understanding of these mechanisms will lead to improved strategies for prevention and control, both nutritional and pharmacologic, of high BP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE REMODELING
RENIN-ANG
II
SYSTEM
IN
CARDIOVASCULAR
Principal Investigator & Institution: Berecek, Kathleen H.; Professor; Physiology and Biophysics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): The major goal of our studies is to identify the molecular mechanisms underlying the role of Ang II in the development and progression of cardiac fibrosis in the spontaneously hypertensive rat (SHR). An additional goal is to determine the mechanisms underlying the ability of early, shortterm application of angiotensin-converting enzyme inhibitors (ACEI) to prevent the development and progression of fibrosis. We have previously found that early, shortterm CAP treatment of SHR prevents cardiac fibrosis and may do this by inhibiting the initiation of a pro-fibrotic environment prior to an increase in BP in SHR. This proposal has 3 specific aims: (1) To determine whether early, short-term treatment of SHR with CAP prevents LV remodeling through prolonged blockade of cardiac RAS and whether or not this effect is independent of blood pressure effects. Cardiac function will be monitored by echocardiography, ex vivo perfusion, and hemodynamic studies. Collagen content, distribution, phenotype, and cross-linking will be determined by a combination of biochemical, morphometric, molecular, biological, and Western blot analyses. Ang II and TGF-beta and its receptors will be monitored by biochemical and molecular biological methods. (2) To determine the cellular and molecular mechanisms underlying Ang II-induced cardiac fibrosis in SHR and how they are inhibited by early, short-term CAP. Expression of collagen isoforms and proteins that regulate collagen synthesis (Ang II receptors, TGF-beta) and proteins that regulate collagen degradation (TIMPs, PAl-l) will be determined by RNase protection assays, and Northern and Western blot analyses. (3) To identify the cellular signal transduction cascades in cardiac fibroblasts that mediate the development of cardiac fibrosis by RAS in hypertension. Signaling intermediates will be determined by Western blot analyses. This proposal will utilize SHR, a well-characterized model of genetic hypertension, and it is the first to study Ang II-dependent mechanisms of collagen synthesis and degradation in vivo and in vitro in cardiac fibroblasts, how they change over time, and how they correlate to cardiac
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function in SHR. These studies will allow us to identify new targets for pharmacological intervention to prevent adverse cardiovascular remodeling in hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF JAK2 IN ANGIOTENSIN II SIGNALING Principal Investigator & Institution: Sayeski, Peter P.; Physiology and Functional Genomics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant):This application outlines the research and career planproposed by Dr. Peter P. Sayeski concerning the mechanisms by which the nonreceptor tyrosine kinase, Jak2, binds the angiotensin II type AT1 receptor and subsequently mediates the angiotensin 11-dependent nuclear accumulation of Stat 1. Angiotensin II is the effector molecule of the renin-angiotensin-aldosterone system which maintains hemodynamic and electrolyte homeostasis. The binding of angiotensin II to the AT1 receptor initiates tyrosine phosphorylation signaling cascades that end with increased vasoconstrictive and mitogenic growth responses. The pharmacological inhibition of this system has been advantageous in a variety of common diseases including hypertension, heart failure and diabetic nephropathy. In response to angiotensin II, Jak2 forms a physical co-association with the AT1 receptor. Previous work by Dr. Sayeski and others suggest that Jak2 plays a critical role in mediating these tyrosine phosphorylation growth responses. The idea that the growth promoting effects of angiotensin II are dependent on Jak2 tyrosine kinase and not heterotrimeric G proteins is a novel concept. Thus, defining the proximal biochemical and cellular events that allow Jak2 to bind the AT1 receptor and subsequently facilitate the translocation of Stat 1 into the nucleus where it modulates gene transcription, will greatly advance this concept. Furthermore, the results of these experiments will be of great interest to the signal transduction community as a whole, at it addresses the fundamental question of how cell surface receptors activate the JakI STAT signaling pathway. The proposed experiments in this application are based on preliminary data using newly created recombinant DNA molecules and novel cell lines. Completion of the proposed Specific Aims will provide a better understanding of (1) the biochemical nature of the AT1/Jak2 physical co-association and (2) the specific role of Jak2 in mediating the angiotensin TIdependent nuclear accumulation of Stat 1. The research will be performed at the University of Florida, which contains state of the art facilities and programs that foster the development of young scientific investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: THE REMODELING
VASCULAR
TRANSCRIPTOME
IN
HYPERTENSIVE
Principal Investigator & Institution: Gibbons, Gary H.; Associate Professor; Medicine; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: The pathogenesis of hypertension-induced target organ damage is related to long-term changes in vessel function and structure. This maladaptive process of vascular remodeling is determined by genetic programs governing cell growth, programmed cell death, inflammation and matrix modulation. The set of genes that are actively expressed by the genome, the transcriptome, is a dynamic determinant of the cellular phenotype and tissue function. The proposed project will test the central hypothesis that target organ damage in hypertension is mediated by the selective up-
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regulation of a "vasculopathic" gene profile induced by the renin-angiotensinaldosterone system (RAAS) and is counterbalanced by an intrinsic set of "vasculoprotective" genes activated by the nuclear receptor PPAR-gamma. Our experimental strategy will incorporate transgenic animals and classic pharmacologic approaches as well as DNA microarray and serial analysis of gene expression (SAGE) technologies. These analytical tools will enable us to define the vascular transcriptome during the pathogenesis of hypertension-induced target organ damage. One outcome of these studies will be the characterization of a common "pharmacogenomic" profile of genes shared by therapeutic strategies that prevent target organ damage that are selectively targeted at modulating the activation of the angiotensin type I receptor, the mineralocorticoid receptor and the PPAR-gamma receptor/transcription factor. The specific aims of the project are to: Define the vascular transcriptome associated with hypertension-induced target organ damage by establishing vascular SAGE libraries in both murine and human primary hypertension. Define the mediator role of the reninangiotensin-aldosterone system as a "vasculo-pathic" determinant of the vascular transcriptome during hypertension-induced target organ damage. Define the mediator role of PPAR-gamma as a "vasculo-protective" determinant of the vascular transcriptome during hypertension-induced target organ damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SENSITIVITY
VANILLOID
SENSITIVE
SENSORY
NERVES
AND
SALT
Principal Investigator & Institution: Wang, Donna H.; Professor; Medicine; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2008 Summary: (provided by applicant): The molecular basis underlying the salt sensitive form of essential hypertension, which is characterized as a polygenic disease with complexities such as "gene-gene" and "environment-gene" interactions, is largely unknown. The overall goal of this project is to define how sensory nerves sense changes in environment, alter its afferent and efferent activities, and interact with other systems to modulate renal function and salt sensitivity of arterial pressure. Toward this goal, we have developed a unique animal model, which shows that degeneration of vanilloidsensitive sensory nerves impairs renal function and renders a rat salt sensitive in terms of blood pressure regulation. Our preliminary data also show that high salt intake increases expression of the vanilloid receptor (VR1) in the renal medulla, and that blockade of the VR1 increases blood pressure in rats fed a high salt diet. These observations have led to the working hypothesis which states that the VR1, expressed in a genetically distinct subpopulation of primary sensory nerves, participates in the maintenance of sodium and fluid homeostasis and plays a significant role in the longterm modulation of salt sensitivity and blood pressure. Three specific aims of the proposal will test the hypotheses: 1) that high salt intake activates renal sensory afferents via stimulation of the VR1; 2) that salt activates the VR1 which results in a suppression of the heightened sympathetic nerve activity occurring in response to salt load, and 3) that blockade of the VR1 impairs the adaptive response of the kidney to high salt intake and leads to increased salt sensitivity of arterial pressure. These studies represent a novel effort to define how vanilloid-sensitive sensory afferents serve as a molecular transducer for sodium and water homeostasis, as well as how "e nvironmentgene" interactions lead to salt sensitive hypertension. These data may force us to revise the ways we think about VR1 ligands. These drugs may have a much broader
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perspective than peripheral pain perception and may serve as specific antihypertensive compounds that can be used to selectively treat salt sensitive hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASCULAR MODULATION
EXTRACELLULAR
SUPEROXIDE
DISMUTASE
Principal Investigator & Institution: Fukai, Tohru; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): Extracellular superoxide dismutase (ecSOD), a major form of SOD expressed in the vasculature, is a "secretory" copper-containing enzyme and plays an important role in regulating blood pressure and endothelial function by modulating the levels of O2 in the extracellular space. Particularly, in angiotensin H-induced hypertension model, the excessive 02 is observed in the vessel wall and the hypertension is ameliorated by treatment with membrane-targeted forms of SOD. Moreover, we have found that blood pressure and 02 production in the vessel were highly elevated in ecSOD-deficient mice infused with angiotensin II. Thus, ecS0D is a potentially important modulator of oxidative phenomena in the pathogenesis of hypertension. Recently, it has been shown that copper chaperones (CCS) are critical for copper transport and delivery to copper containing enzymes. Our preliminary data strongly suggests that CCS with signal peptide (CCS-SP) which targets to Golgi plays an important role in the transport of copper to ecSOD, which is required for full activity of the ecSOD. We will propose the following specific aim to address how ecSOD activity is controlled by copper transport system such as CCS and copper transporter in the yeast system, vascular cells and in vivo model of hypertension. In aim 1, we will characterize a role of copper transport system for full expression of ecSOD activity using the yeast system. First, by generating several CCS-SP cDNA constructs including the truncated form, we will determine which region is critical for copper loading-to ecSOD. Second, we will determine if copper loading to ecSOD requires MNK, a copper transporter in the trans-Golgi network, using the yeast strain deficient in MNK. In aim 2, we will identify endogenous copper chaperone for ecSOD in human aortic smooth muscle cells (HASM) that highly expresses ecSOD, by using the highly conserved region of CCS as a probe that have detected novel CCS-like transcript and protein in HASM. Next, we will determine if copper delivery to ecSOD requires MTNK in mammalian cells, by using the murine MNK-mutant fibroblast and aorta from MNK-mutant mice. In aim 3, we will examine the role of copper transport system for ecSOD in blood pressure, vascular O2 production and endothelial function in angiotensin II induced hypertension by using MNK-mutant mice. These studies will provide new insight into a copper transport system for ecSOD as a novel modulator of oxidative stress linked to the pathogenesis of hypertension and as essential to anti-oxidant therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASOACTIVE HORMONES AND BLOOD PRESSURE REGULATION Principal Investigator & Institution: Nasjletti, Alberto; Professor; Pharmacology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 31-JAN-2005 Summary: This proposal focuses on the function and regulation of the vascular hemeheme oxygenase-carbon monoxide system in relation to peripheral mechanisms of vasomotor control in normotensive and hypertensive rats. Four major hypotheses will
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be examined. First, heme oxygenase-derived carbon monoxide is manufactured tonically, by small monoxide of vascular origin inhibits myogenic behavior and responsiveness to constrictor hormones in arterioles and small arteries. Third, the hemeheme oxygenase-carbon monoxide system contributes to the implementation of peripheral anti-hypertensive mechanisms. Fourth, the heme-heme oxygenase-carbon monoxide system contributes to the implementation of peripheral anti-hypertensive mechanisms. Fourth, high oxidative stress in arterial tissues of rats with angiotensindependent hypertension promotes vascular production of heme oxygenase products which, in turn, subserve adaptive anti-hypertensive and anti-oxidative functions. In testing these hypotheses, the following the following specific aims will be addressed in normotensive and hypertensive rats. AIM 1: To Characterize the Status of the HemeHeme Oxygenase System of Arterial Vessels in Terms of Heme Oxygenase(s) Protein Level and Activity and Ability to Manufacture Carbon Monoxide. We will contrast small and large arterial vessels of normotensive and hypertensive rats in terms of ability to manufacture carbon monoxide and levels heme oxygenase protein and activity. AIM 2: To Define the Influence of Vascular Heme Oxygenase Product Formation on Vasomoter Function. We will examine the effect of interventions that increase or decrease the activity of the vascular heme-heme oxygenase system on myogenic responses and reactivity to constrictor agonist in small arteries and arterioles. AIM 3: To Determine the Effect of Interventions that Alter Heme-Oxygenase Product Formation on the Blood Pressure on Normotensive Rats and Spontaneously Hypertensive Rats. We will examine the hemodynamic response to interventions that decrease (heme oxygenase inhibitor; heme oxygenase antisense oligodeoxynucleotides) heme oxygenase activity or level of expression on blood pressure. Aim 4: To Explore Relationships Between Vascular Heme Oxygenase Product Formation and Oxidative Stress in Rats with Angiotensin-Dependent Hypertension. We will explore the effect of anti-oxidants on the vascular heme-heme oxygenase system and of heme oxygenase inhibitors on indices of oxidative stress in hypertensive rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASODEPRESSOR MECHANISMS MEDIATED BY ANGIOTENSIN (1-7) Principal Investigator & Institution: Ferrario, Carlos M.; Dewitt Cordell Professor of Surgical Res; Wake Forest University 1834 Wake Forest Road Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Angiotensin I (Ang I) is cleaved into a number of active fragments, of which angiotensin II (ANG II) remains the most widely studied peptide. However, we first reported in 1988 the existence of another angiotensin peptide-the heptapeptide angiotensin-(1-7) which possesses important properties as a vasodilator, diuretic and natriuretic agent by stimulation of the release of vasodilator prostaglandins, potentiation of the actions of bradykinin, and release of nitric oxide. The vasodepressor and anti-mitogenic effects of Ang-(1-7) suggest that it may act to oppose the actions of Ang II. In agreement with this interpretation, we found that inhibition of Ang-(1-7) suggest that it may act to oppose the actions of Ang II. In agreement with this interpretation, we found that inhibition of Ang-(1-7) synthesis or neutralization of Ang(1-7) activity with specific antibodies and selective receptor antagonists produces hypertensive responses more marked in animals with blockade of Ang II activity or salt depletion. The primary objective of this proposal will be to show that Ang-(1-7) acts as a negative feedback stabilizer of Ang II in the regulation of arterial pressure and sodium excretion. Four Specific Aims are proposed to accomplish this objective. Specific Aim 1
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will investigate the hypothesis that blunted vasodepressor activity of Ang-(1-7) contributes to the hypertension of SHR and [mREN-2]27 transgenic hypertensive rats, whereas further activation of the RAS by salt depletion exposes Ang-(1- 7)-mediated vasodilator mechanisms. Specific Aim 2 will show whether Ang-(1-7) produced locally acts at a unique receptor to modulate the renal pressure natriuresis-diuresis curve. Specific Aim 3 will evaluate the potent vasodilator actions of Ang-(1-7) in the rat mesenteric microcirculation to assess the paracrine actions of the peptide and ascertain the mechanism that contributes to the loss of vasodepressor activity in SHR and [mRen2]27 hypertensive animals. Specific Aim 4 will explore a new facet of the regulation of the function of Ang-(1-7) by characterizing the mechanisms for Ang-(1-7) clearance from the circulation through: 1)-the investigation of the role of ACE as the primary enzyme involved in Ang-(1-7) degradation; and 2)- the characterization of the receptor(s) that participates in the removal of the heptapeptide from cell surfaces. Hemodynamic studies are complemented with measurements of angiotensins in blood, urine and tissues and correlate assays in urine of prostaglandins and cGMP. The receptor(s) mediating the hemodynamic and sodium excretory actions of Ang-(1-7) will be characterized pharmacologically by contrasting the effects of both selective and nonselective Ang II antagonists. The proposed studies may provide a new understanding of the biochemical physiology of the renin angiotensin system and the mode of action of therapies that depend upon inhibition of ACE and Ang II receptor blockade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “aldosterone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for aldosterone in the PubMed Central database: •
A Comparison of the Metabolism of Radioactive 17-Isoaldosterone and Aldosterone Administered Intravenously and Orally to Normal Human Subjects. by Flood C, Pincus G, Tait JF, Tait SA, Willoughby S.; 1967 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297074
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A Decreased Metabolic Clearance Rate of Aldosterone in Benign Essential Hypertension. by Nowaczynski W, Kuchel O, Genest J.; 1971 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292153
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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•
A Specific Role for Saline or the Sodium Ion in the Regulation of Renin and Aldosterone Secretion. by Tuck ML, Dluhy RG, Williams GH.; 1974 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333083
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Abnormally Sustained Aldosterone Secretion during Salt Loading in Patients with Various Forms of Benign Hypertension; Relation to Plasma Renin Activity. by Collins RD, Weinberger MH, Dowdy AJ, Nokes GW, Gonzales CM, Luetscher JA.; 1970 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322615
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Activation of Aldosterone Secretion in Primary Aldosteronism. by Spark RF, Dale SL, Kahn PC, Melby JC.; 1969 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322195
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Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome. by Arrighi I, Bloch-Faure M, Grahammer F, Bleich M, Warth R, Mengual R, Drici MD, Barhanin J, Meneton P.; 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37514
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Attenuation of Angiotensin II- and III-induced Aldosterone Release by Prostaglandin Synthesis Inhibitors. by Campbell WB, Gomez-Sanchez CE, Adams BV, Schmitz JM, Itskovitz HD.; 1979 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371307
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Circadian Rhythm of Plasma Aldosterone Concentration in Patients with Primary Aldosteronism. by Kem DC, Weinberger MH, Gomez-Sanchez C, Kramer NJ, Lerman R, Furuyama S, Nugent CA.; 1973 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333030
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CONCERNING THE ROLE OF ARTERIAL BARORECEPTORS IN THE CONTROL OF ALDOSTERONE SECRETION. by Carpenter CC, Davis JO, Ayers CR.; 1961 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=290828
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Decreased Plasma Clearance and Hepatic Extraction of Aldosterone in Patients with Heart Failure. by Camargo CA, Dowdy AJ, Hancock EW, Luetscher JA.; 1965 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292486
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Distribution, conjugation, and excretion of labeled aldosterone in congestive heart failure and in controls with normal circulation: development and testing of a model with an analog computer. by Cheville RA, Luetscher JA, Hancock EW, Dowdy AJ, Nokes GW.; 1966 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292806
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Dopamine Inhibits Angiotensin-Stimulated Aldosterone Biosynthesis in Bovine Adrenal Cells. by Mc Kenna TJ, Island DP, Nicholson WE, Liddle GW.; 1979 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372116
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Effect of aldosterone on the coupling between H+ transport and glucose oxidation. by Al-Awqati Q.; 1977 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372480
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Effects of [beta]-Lipotropin and [beta]-Lipotropin-derived Peptides on Aldosterone Production in the Rat Adrenal Gland. by Matsuoka H, Mulrow PJ, Franco-Saenz R.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370857
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Effects of aldosterone and potassium-sparing diuretics on electrical potential differences across the distal nephron. by Gross JB, Kokko JP.; 1977 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333334
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Endothelin binding to cultured calf adrenal zona glomerulosa cells and stimulation of aldosterone secretion. by Cozza EN, Gomez-Sanchez CE, Foecking MF, Chiou S.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329753
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Evidence for a mucosal effect of aldosterone on sodium transport in the toad bladder. by Sharp GW, Coggins CH, Lichtenstein NS, Leaf A.; 1966 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292846
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Genetic variation in aldosterone synthase predicts plasma glucose levels. by Ranade K, Wu KD, Risch N, Olivier M, Pei D, Hsiao CF, Chuang LM, Ho LT, Jorgenson E, Pesich R, Chen YD, Dzau V, Lin A, Olshen RA, Curb D, Cox DR, Botstein D.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60851
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Impaired Aldosterone Production in "Salt-losing" Congenital Adrenal Hyperplasia. by Bryan GT, Kliman B, Bartter FC.; 1965 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292576
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Kinetics of RNA Synthesis in Toad Bladder Epithelium: Action of Aldosterone during the Latent Period. by Vancra P, Sharp GW, Malt RA.; 1971 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291961
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Metabolism and Rate of Secretion of Aldosterone in the Bullfrog. by Ulick S, Feinholtz E.; 1968 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297417
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Metabolism of Aldosterone in Several Experimental Situations with Altered Aldosterone Secretion. by Davis JO, Olichney MJ, Brown TC, Binnion PF.; 1965 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292624
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Modulation of Plasma Aldosterone Concentration by Plasma Potassium in Anephric Man in the Absence of a Change in Potassium Balance. by Cooke CR, Horvath JS, Moore MA, Bledsoe T, Walker WG.; 1973 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302577
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ON THE MECHANISM OF ACTION OF ALDOSTERONE ON SODIUM TRANSPORT: THE ROLE OF PROTEIN SYNTHESIS. by Edelman IS, Bogoroch R, Porter GA.; 1963 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221291
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ON THE MECHANISM OF ACTION OF ALDOSTERONE ON SODIUM TRANSPORT: THE ROLE OF RNA SYNTHESIS. by Porter GA, Bogoroch R, Edelman IS.; 1964 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=300448
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Plasma Aldosterone Concentration at Delivery and during the Newborn Period. by Beitins IZ, Bayard F, Levitsky L, Ances IG, Kowarski A, Migeon CJ.; 1972 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302137
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Postural Augmentation of Plasma Renin Activity and Aldosterone Excretion in Normal People. by Cohen EL, Conn JW, Rovner DR.; 1967 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297062
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Prolonged Infusions of Angiotensin II and Norepinephrine and Blood Pressure, Electrolyte Balance, and Aldosterone and Cortisol Secretion in Normal Man and in Cirrhosis with Ascites. by Ames RP, Borkowski AJ, Sicinski AM, Laragh JH.; 1965 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292592
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Pyridine nucleotide redox state parallels production of aldosterone in potassiumstimulated adrenal glomerulosa cells. by Pralong WF, Hunyady L, Varnai P, Wollheim CB, Spat A.; 1992 Jan 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48190
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Rapid Activation of Na+/H+ Exchange by Aldosterone in Renal Epithelial Cells Requires Ca2+ and Stimulation of a Plasma Membrane Proton Conductance. by Gekle M, Golenhofen N, Oberleithner H, Silbernagl S.; 1996 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38414
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Regulation of active sodium and potassium transport in the distal colon of the rat. Role of the aldosterone and glucocorticoid receptors. by Turnamian SG, Binder HJ.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304073
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Regulation of prostasin by aldosterone in the kidney. by Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K, Shiraishi N, Nonoguchi H, Chen LM, Chai KX, Chao J, Tomita K.; 2002 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150850
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Relation between potassium balance and aldosterone secretion in normal subjects and in patients with hypertensive or renal tubular disease. by Cannon PJ, Ames RP, Laragh JH.; 1966 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292766
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RELATION OF RENIN, ANGIOTENSIN II, AND EXPERIMENTAL RENAL HYPERTENSION TO ALDOSTERONE SECRETION. by Carpenter CC, Davis JO, Ayers CR.; 1961 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=290907
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Role of angiotensin II in potassium-mediated stimulation of aldosterone secretion in the dog. by Pratt JH.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370270
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Secondary effect of aldosterone on Na-KATPase activity in the rabbit cortical collecting tubule. by Petty KJ, Kokko JP, Marver D.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370955
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SECRETION RATE OF ALDOSTERONE IN NORMAL PREGNANCY. by Watanabe M, Meeker CI, Gray MJ, Sims EA, Solomon S.; 1963 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289441
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Site of Stimulation of Aldosterone Biosynthesis by Angiotensin and Potassium. by Brown RD, Strott CA, Liddle GW.; 1972 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292278
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Sites of Action of Sodium Depletion on Aldosterone Biosynthesis in the Dog. by Davis WW, Burwell LR, Casper AG, Bartter FC.; 1968 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297298
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Sodium-independent in vitro induction of Na+,K+-ATPase by aldosterone in renal target cells: permissive effect of triiodothyronine. by Barlet-Bas C, Khadouri C, Marsy S, Doucet A.; 1988 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279844
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Spironolactone. An aldosterone agonist in the stimulation of H+ secretion by turtle urinary bladder. by Mueller A, Steinmetz PR.; 1978 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372693
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Stimulation and Suppression of Aldosterone in Plasma of Normal Man and in Primary Aldosteronism. by Horton R.; 1969 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322344
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STIMULATION OF ACTIVE SODIUM TRANSPORT BY THE ISOLATED TOAD BLADDER WITH ALDOSTERONE IN VITRO. by Crabbe J.; 1961 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=290914
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Stimulation of Aldosterone Biosynthesis in Adrenal Mitochondria by Sodium Depletion. by Marusic ET, Mulrow PJ.; 1967 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292960
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Studies of the Control of Plasma Aldosterone Concentration in Normal Man III. RESPONSE TO SODIUM CHLORIDE INFUSION. by Williams GH, Tuck ML, Rose LI, Dluhy RG, Underwood RH.; 1972 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332963
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Studies of the Control of Plasma Aldosterone Concentration in Normal Man. I. RESPONSE TO POSTURE, ACUTE AND CHRONIC VOLUME DEPLETION, AND SODIUM LOADING. by Williams GH, Cain JP, Dluhy RG, Underwood RH.; 1972 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292320
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Studies of the Control of Plasma Aldosterone Concentration in Normal Man. II. EFFECT OF DIETARY POTASSIUM AND ACUTE POTASSIUM INFUSION. by Dluhy RG, Axelrod L, Underwood RH, Williams GH.; 1972 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292351
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Studies of the mechanism through which sodium depletion increases aldosterone biosynthesis in man. by Bledsoe T, Island DP, Liddle GW.; 1966 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292726
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Studies on the binding of aldosterone in the toad bladder. by Sharp GW, Komack CL, Leaf A.; 1966 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292719
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The Action of Aldosterone and Related Corticosteroids on Sodium Transport across the Toad Bladder. by Porter GA, Edelman IS.; 1964 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289538
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THE BINDING OF ALDOSTERONE TO PLASMA PROTEINS IN NORMAL, PREGNANT, AND STEROID-TREATED WOMEN. by Meyer CJ, Layne DS, Tait JF, Pincus G.; 1961 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=290860
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THE EFFECT OF ACTH, RENIN, ANGIOTENSIN II, AND VARIOUS PRECURSORS ON BIOSYNTHESIS OF ALDOSTERONE BY ADRENAL SLICES. by Kaplan NM, Bartter FC.; 1962 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=290975
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THE EFFECT OF AORTIC CONSTRICTION ON ALDOSTERONE SECRETION IN HYPOPHYSECTOMIZED DOGS. by Ganong WF, Mulrow PJ.; 1962 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291061
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THE EFFECT OF HEMORRHAGE UPON ALDOSTERONE SECRETION IN NORMAL AND HYPOPHYSECTOMIZED DOGS. by Mulrow PJ, Ganong WF.; 1961 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=290755
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THE EFFECTS OF ALTERATIONS OF PLASMA SODIUM AND POTASSIUM CONCENTRATION ON ALDOSTERONE SECRETION. by Davis JO, Urquhart J, Higgins JT Jr.; 1963 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289324
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The Effects of Estradiol and Estriol on Plasma Levels of Cortisol and Thyroid Hormone-Binding Globulins and on Aldosterone and Cortisol Secretion Rates in Man. by Katz FH, Kappas A.; 1967 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292927
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THE METABOLIC CLEARANCE RATE OF ALDOSTERONE IN PREGNANT AND NONPREGNANT SUBJECTS ESTIMATED BY BOTH SINGLE-INJECTION AND CONSTANT-INFUSION METHODS. by Tait JF, Little B, Tait SA, Flood C.; 1962 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291143
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The Metabolism and Secretion of Aldosterone in Elderly Subjects. by Flood C, Gherondache C, Pincus G, Tait JF, Tait SA, Willoughby S.; 1967 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297100
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THE METABOLISM OF ALDOSTERONE IN NORMAL SUBJECTS AND IN PATIENTS WITH HEPATIC CIRRHOSIS. by Coppage WS Jr, Island DP, Cooner AE, Liddle GW.; 1962 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291084
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The Metabolism of Orally and Intravenously Administered Labeled Aldosterone in Pregnant Subjects. by Tait JF, Little B.; 1968 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297408
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The Renal Tubular Handling of Aldosterone and Its Acid-Labile Conjugate. by Scurry MT, Shear L, Barry KG.; 1968 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297166
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THE ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN THE CONTROL OF ALDOSTERONE SECRETION. by Davis JO, Hartroft PM, Titus EO, Carpenter CC, Ayers CR, Spiegel HE.; 1962 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289236
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The Steroid Content of Adrenal Adenomas and Measurements of Aldosterone Production in Patients with Essential Hypertension and Primary Aldosteronism. by Kaplan NM.; 1967 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297075
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Transcriptome of a mouse kidney cortical collecting duct cell line: Effects of aldosterone and vasopressin. by Robert-Nicoud M, Flahaut M, Elalouf JM, Nicod M, Salinas M, Bens M, Doucet A, Wincker P, Artiguenave F, Horisberger JD, Vandewalle A, Rossier BC, Firsov D.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30204
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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 aldosterone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “aldosterone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for aldosterone (hyperlinks lead to article summaries): •
Activity of the renin-angiotensin-aldosterone axis is dependent on the occurrence of edema in growth hormone (GH)-deficient adults treated with GH. Author(s): Hayes FJ, Fiad TM, McKenna TJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 January; 82(1): 3223. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8989283
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Acute aldosterone antagonism improves cardiac vagal control in humans. Author(s): Fletcher J, Buch AN, Routledge HC, Chowdhary S, Coote JH, Townend JN. Source: Journal of the American College of Cardiology. 2004 April 7; 43(7): 1270-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15063441
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Adrenal tumor producing 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone and aldosterone. Author(s): Toyoda Y, Mizukoshi M, Umemoto M, Kuchii M, Ueyama K, Tomimoto S, Baba A, Shima H, Nishio I, Masuyama Y. Source: Intern Med. 1996 February; 35(2): 123-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8680100
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Aldosterone action, sodium channels and inherited disease. Author(s): Fuller PJ, Lim-Tio S. Source: The Journal of Endocrinology. 1996 March; 148(3): 387-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8778216
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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Aldosterone and heart failure. Author(s): Zannad F. Source: European Heart Journal. 1995 December; 16 Suppl N: 98-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8682070
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Aldosterone and its mechanism of action: more questions than answers. Author(s): Fuller PJ. Source: Aust N Z J Med. 1995 December; 25(6): 800-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8770356
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Aldosterone antagonism and arterial stiffness. Author(s): Safar ME, Avolio A. Source: Hypertension. 2004 February; 43(2): E3; Author Reply E3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756124
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Aldosterone blockade in patients with acute myocardial infarction. Author(s): Solomon HA. Source: Circulation. 2003 December 23; 108(25): E173; Author Reply E173. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691030
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Aldosterone changes during angiotensin III and potassium infusions in patients with primary aldosteronism. Author(s): Plouin PF, Massien-Simon C, Azizi M. Source: Clinical Endocrinology. 1996 August; 45(2): 243-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8881460
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Aldosterone cord levels in preterm newborn infants. Author(s): Procianoy RS, de Oliveira-Filho EA. Source: Acta Paediatrica (Oslo, Norway : 1992). 1996 May; 85(5): 611-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8827108
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Aldosterone escape during ACE inhibitor therapy in chronic heart failure. Author(s): Struthers AD. Source: European Heart Journal. 1995 December; 16 Suppl N: 103-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8682054
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Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. Author(s): Struthers AD. Source: Journal of Cardiac Failure. 1996 March; 2(1): 47-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8798105
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Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Author(s): Calhoun DA, Nishizaka MK, Zaman MA, Harding SM. Source: Chest. 2004 January; 125(1): 112-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718429
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Aldosterone response to metoclopramide in patients with prolactinoma: effect of short-term bromocriptine treatment. Author(s): Zacharieva S, Stoeva I, Andreeva M, Kalinov K, Matrozov P, Andonova K. Source: Methods Find Exp Clin Pharmacol. 1996 November; 18(9): 593-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9010834
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Aldosterone responses to hyperkalemia in healthy elderly humans. Author(s): Mulkerrin E, Epstein FH, Clark BA. Source: Journal of the American Society of Nephrology : Jasn. 1995 November; 6(5): 1459-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8589323
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Aldosterone synthase alleles and cardiovascular phenotype in young adults. Author(s): Sarzani R, Salvi F, Dessi-Fulgheri P, Catalini R, Mazzara D, Cola G, Siragusa N, Spagnolo D, Ercolani P, Gesuita R, Carle F, Rappelli A. Source: Journal of Human Hypertension. 2003 December; 17(12): 859-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14704730
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Aldosterone: intracellular receptors in human heart. Author(s): Bonvalet JP, Alfaidy N, Farman N, Lombes M. Source: European Heart Journal. 1995 December; 16 Suppl N: 92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8682069
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Aldosterone-producing adenomas do not contain glucocorticoid-remediable aldosteronism chimeric gene duplications. Author(s): Carroll J, Dluhy R, Fallo F, Pistorello M, Bradwin G, Gomez-Sanchez CE, Mortensen R. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 December; 81(12): 4310-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8954032
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Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension. Author(s): Stella P, Bigatti G, Tizzoni L, Barlassina C, Lanzani C, Bianchi G, Cusi D. Source: Journal of the American College of Cardiology. 2004 January 21; 43(2): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736447
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Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass. Author(s): Schunkert H, Hense HW, Muscholl M, Luchner A, Kurzinger S, Danser AH, Riegger GA. Source: Heart (British Cardiac Society). 1997 January; 77(1): 24-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9038690
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Balancing diuretic therapy in heart failure: loop diuretics, thiazides, and aldosterone antagonists. Author(s): Paul S. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 November-December; 8(6): 307-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12461320
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Basal and ACTH-stimulated cortisol and aldosterone release from adrenocortical adenomas in vitro. Author(s): Grondal S, Grimelius L, Thoren M, Hamberger B. Source: The European Journal of Surgery = Acta Chirurgica. 1991 March; 157(3): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678626
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Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects. Author(s): Blumenfeld JD, Sealey JE, Mann SJ, Bragat A, Marion R, Pecker MS, Sotelo J, August P, Pickering TG, Laragh JH. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1999 May; 12(5): 451-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10342782
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Bilateral aldosterone-producing adenomas in two patients diagnosed by immunohistochemical analysis of steroidogenic enzymes. Author(s): Watanabe N, Tsunoda K, Sasano H, Omata K, Imai Y, Ito S, Abe K. Source: The Tohoku Journal of Experimental Medicine. 1996 June; 179(2): 123-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8875768
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Biochemical correction in the syndrome of hypertension and hyperkalaemia by severe dietary salt restriction suggests renin-aldosterone suppression critical in pathophysiology. Author(s): Klemm SA, Gordon RD, Tunny TJ, Finn WL. Source: Clinical and Experimental Pharmacology & Physiology. 1990 March; 17(3): 1915. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2187635
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Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients. Author(s): Goldberg MR, Bradstreet TE, McWilliams EJ, Tanaka WK, Lipert S, Bjornsson TD, Waldman SA, Osborne B, Pivadori L, Lewis G, et al. Source: Hypertension. 1995 January; 25(1): 37-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7843751
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Biochemical evidence of aldosterone overproduction and abnormal regulation in normotensive individuals with familial hyperaldosteronism type I. Author(s): Stowasser M, Huggard PR, Rossetti TR, Bachmann AW, Gordon RD. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 November; 84(11): 4031-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10566645
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Biochemical markers in the acute stage of head injury--aldosterone and CK-BB. Author(s): Takahashi H, Sato H, Tsuji Y. Source: Neurol Med Chir (Tokyo). 1989 March; 29(3): 192-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2477723
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Biological day-to-day variation and reference change limits of serum cortisol and aldosterone in healthy young men on unrestricted diets. Author(s): Ahokoski O, Virtanen A, Kairisto V, Scheinin H, Huupponen R, Irjala K. Source: Clinical Chemistry. 1999 July; 45(7): 1097-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10388492
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Blockade of the renin-angiotensin system at different sites: effect on renin, angiotensin and aldosterone. Author(s): Abdelrahman AM, Burrell LM, Johnston CI. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1993 April; 11(3): S23-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8315514
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Blockade of the renin-angiotensin-aldosterone system and renal protection in diabetes mellitus. Author(s): Parving HH. Source: J Renin Angiotensin Aldosterone Syst. 2000 March; 1(1): 30-1. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967794
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Blockade of the renin-angiotensin-aldosterone system prevents growth hormoneinduced fluid retention in humans. Author(s): Moller J, Moller N, Frandsen E, Wolthers T, Jorgensen JO, Christiansen JS. Source: The American Journal of Physiology. 1997 May; 272(5 Pt 1): E803-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9176179
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Blockade of the renin-angiotensin-aldosterone system with combination angiotensin receptor antagonist and ACE inhibitor therapy: observations from Val-HeFT and CALM. Author(s): Chin BS, Lip GY. Source: Journal of Human Hypertension. 2001 February; 15(2): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317186
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Blocking the renin-angiotensin-aldosterone system or lowering the blood pressure: does EUROPA help? Author(s): Mackay JA. Source: J Renin Angiotensin Aldosterone Syst. 2003 December; 4(4): 205-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14689366
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Blood pressure and the renin-angiotensin-aldosterone system in children receiving recombinant human growth hormone. Author(s): Barton JS, Hindmarsh PC, Preece MA, Brook CG. Source: Clinical Endocrinology. 1993 March; 38(3): 245-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8458096
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Blood pressure regulation, peripheral renin activity and aldosterone in patients with pyelonephritic renal scarring. Author(s): Jacobson SH. Source: Acta Physiologica Scandinavica. 1987 October; 131(2): 242-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3314352
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Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol. Author(s): Mander AJ, Young A, MacDonald TM, Williams BC, Waugh CJ, Edwards CR. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 1989; 24(5): 409-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2818749
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Blunted aldosterone responsiveness to angiotensin II in normotensive subjects with familial predisposition to essential hypertension. Author(s): Beretta-Piccoli C, Pusterla C, Stadler P, Weidmann P. Source: Journal of Hypertension. 1988 January; 6(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3351294
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Bopindolol: long-term effects on blood pressure, renal function, plasma renin activity, and plasma aldosterone in mild-to-moderate essential hypertension. Author(s): Shohat J, Modan M, Rosenfeld JB. Source: Fundamental & Clinical Pharmacology. 1989; 3(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2565862
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Calcified aldosterone-producing adrenocortical adenoma. Author(s): Jelic TM, Triest W, Sheils J, Porter D, Cherry D, Baltaro RJ, Sheils W Jr, Driscoll HK, Solanki HP, Molina R, Molina L, Chertow BS. Source: Clinical Imaging. 1996 January-March; 20(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846310
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Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Author(s): Condon JC, Pezzi V, Drummond BM, Yin S, Rainey WE. Source: Endocrinology. 2002 September; 143(9): 3651-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12193581
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Cardiovascular benefits of aldosterone receptor antagonists. Author(s): Williams GH. Source: Climacteric : the Journal of the International Menopause Society. 2003 October; 6 Suppl 3: 29-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15018246
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Cardiovascular endocrinology 1: aldosterone function in diabetes mellitus: effects on cardiovascular and renal disease. Author(s): McFarlane SI, Sowers JR. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 516-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574172
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Catecholamines, renin-angiotensin-aldosterone system, and atrial natriuretic peptide at rest and during submaximal exercise in patients with congestive heart failure. Author(s): Kinugawa T, Ogino K, Kitamura H, Saitoh M, Omodani H, Osaki S, Hisatome I, Miyakoda H. Source: The American Journal of the Medical Sciences. 1996 September; 312(3): 110-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8783676
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Cell membrane cation transport systems during aldosterone antagonism. Author(s): Lijnen P, Petrov V. Source: Journal of Cardiovascular Pharmacology. 1996 April; 27(4): 462-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8847860
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Cholecystokinin (CCK) stimulates aldosterone secretion from human adrenocortical cells via CCK2 receptors coupled to the adenylate cyclase/protein kinase A signaling cascade. Author(s): Mazzocchi G, Malendowicz LK, Aragona F, Spinazzi R, Nussdorfer GG. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 March; 89(3): 127784. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001623
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Chromatographic system for the simultaneous measurement of plasma 18-hydroxy11-deoxycorticosterone and 18-hydroxycorticosterone by radioimmunoassay: reference data for neonates and infants and its application in aldosterone-synthase deficiency. Author(s): Riepe FG, Krone N, Peter M, Sippell WG, Partsch CJ. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 March 5; 785(2): 293-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12554142
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Circadian rhythms of plasma atriopeptin, plasma renin activity and plasma aldosterone in patients with hepatorenal syndrome. Author(s): Pasqualetti P, Festuccia V, Collacciani A, Di Lauro G, Casale R. Source: Life Sciences. 1997; 60(4-5): 289-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9010484
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Circulating aldosterone levels are unexpectedly low in children with acute meningococcal disease. Author(s): Lichtarowicz-Krynska EJ, Cole TJ, Camacho-Hubner C, Britto J, Levin M, Klein N, Aynsley-Green A. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 March; 89(3): 14104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001642
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Clinical implications of aldosterone blockade. Author(s): Weber MA. Source: American Heart Journal. 2002 November; 144(5 Suppl): S12-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422136
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Clinical implications of local renin-angiotensin-aldosterone systems. Author(s): Frohlich ED. Source: Current Cardiology Reports. 2003 July; 5(4): 247-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801441
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Clinical studies on the blockade of the renin-angiotensin-aldosterone-system. Author(s): Hennig L. Source: Clinical Nephrology. 2003 July; 60 Suppl 1: S53-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940534
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Combining renin-angiotensin-aldosterone system blockade with diuretic therapy for treatment of hypertension. Author(s): Motwani JG. Source: J Renin Angiotensin Aldosterone Syst. 2002 June; 3(2): 72-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12228846
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Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene. Author(s): Kayes-Wandover KM, Tannin GM, Shulman D, Peled D, Jones KL, Karaviti L, White PC. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 November; 86(11): 5379-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701710
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Contrasting associations between aldosterone synthase gene polymorphisms and essential hypertension in blacks and in whites. Author(s): Zhu H, Sagnella GA, Dong Y, Miller MA, Onipinla A, Markandu ND, MacGregor GA. Source: Journal of Hypertension. 2003 January; 21(1): 87-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544440
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Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Author(s): Spat A, Hunyady L. Source: Physiological Reviews. 2004 April; 84(2): 489-539. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044681
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Correction of the nomenclature and mechanism of the aldosterone biosynthetic defects. Author(s): Ulick S. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 March; 81(3): 1299300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8772616
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Cyclosporine a and FK506 inhibit transcriptional activity of the human mineralocorticoid receptor: a cell-based model to investigate partial aldosterone resistance in kidney transplantation. Author(s): Deppe CE, Heering PJ, Viengchareun S, Grabensee B, Farman N, Lombes M. Source: Endocrinology. 2002 May; 143(5): 1932-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956176
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Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 micro g) ACTH test in subjects with preclinical adrenal autoimmunity. Author(s): Laureti S, Candeloro P, Aglietti MC, Giordano R, Arvat E, Ghigo E, Santeusanio F, Falorni A. Source: Clinical Endocrinology. 2002 November; 57(5): 677-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390344
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Deletion hybrid genes, due to unequal crossing over between CYP11B1 (11betahydroxylase) and CYP11B2(aldosterone synthase) cause steroid 11beta-hydroxylase deficiency and congenital adrenal hyperplasia. Author(s): Portrat S, Mulatero P, Curnow KM, Chaussain JL, Morel Y, Pascoe L. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 July; 86(7): 3197201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443188
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Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): screening in fission yeast and evaluation of selectivity in V79 cells. Author(s): Ehmer PB, Bureik M, Bernhardt R, Muller U, Hartmann RW. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 June; 81(2): 173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137808
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Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene. Author(s): Mulatero P, Veglio F, Pilon C, Rabbia F, Zocchi C, Limone P, Boscaro M, Sonino N, Fallo F. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 July; 83(7): 2573-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9661646
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Different allelic patterns at chromosome 11q13 in paired aldosterone-producing tumours and blood DNA. Author(s): Gordon R, Gartside M, Tunny T, Stowasser M. Source: Clinical and Experimental Pharmacology & Physiology. 1996 June-July; 23(6-7): 594-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8800595
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Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma. Author(s): Chen YM, Wu KD, Hu-Tsai MI, Chu JS, Lai MK, Hsieh BS. Source: Molecular and Cellular Endocrinology. 1999 June 25; 152(1-2): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10432222
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Differential regulation of 11 beta-hydroxylase and aldosterone synthase in human adrenocortical H295R cells. Author(s): Denner K, Rainey WE, Pezzi V, Bird IM, Bernhardt R, Mathis JM. Source: Molecular and Cellular Endocrinology. 1996 July 23; 121(1): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8865169
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Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1. Author(s): Bassett MH, Zhang Y, Clyne C, White PC, Rainey WE. Source: Journal of Molecular Endocrinology. 2002 April; 28(2): 125-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932209
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Dihydrospirorenone, a new progestogen with antimineralocorticoid activity: effects on ovulation, electrolyte excretion, and the renin-aldosterone system in normal women. Author(s): Oelkers W, Berger V, Bolik A, Bahr V, Hazard B, Beier S, Elger W, Heithecker A. Source: The Journal of Clinical Endocrinology and Metabolism. 1991 October; 73(4): 83742. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1890155
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Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Author(s): Hartmann RW, Muller U, Ehmer PB. Source: European Journal of Medicinal Chemistry. 2003 April; 38(4): 363-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750023
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Disorders of the aldosterone synthase and steroid 11beta-hydroxylase deficiencies. Author(s): Peter M, Dubuis JM, Sippell WG. Source: Hormone Research. 1999; 51(5): 211-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10559665
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Diurnal urinary excretion of cortisol and aldosterone in kidney graft recipients. Author(s): Stefanovic V, Ivic M, Mitic M. Source: Pathologie-Biologie. 1995 November; 43(9): 766-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8746098
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Do diuretics and aldosterone receptor antagonists improve ventricular remodeling? Author(s): Pitt B. Source: Journal of Cardiac Failure. 2002 December; 8(6 Suppl): S491-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12555163
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Does aldosterone modulate central control of blood pressure? Author(s): Tuck ML. Source: Journal of Hypertension. 2002 June; 20(6): 1079-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023673
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Does industrial environment influence the prevalence of arterial hypertension, plasma cholesterol and uric acid concentration and activity of the renin-aldosterone system? Author(s): Wiecek A, Kokot F. Source: Przegl Lek. 1996; 53(4): 356-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8711191
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Dopaminergic modulation of aldosterone secretions on changes of sodium intake in aldosterone-producing adenoma. Author(s): Wu KD, Chen YM, Chu TS, Chueh SC, Tsai GC, Tseng YZ, Hsieh BS. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 July; 15(7 Pt 1): 609-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118908
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Dopaminergic regulation of aldosterone secretion: its pathophysiologic significance in subsets of primary aldosteronism. Author(s): Naruse M, Naruse K, Yoshimoto T, Tanaka M, Tanabe A, Imaki T, Shibasaki T, Demura R, Demura H. Source: Hypertens Res. 1995 June; 18 Suppl 1: S59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8529076
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Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Author(s): Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, Veglio F. Source: Hypertension. 2002 December; 40(6): 897-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12468576
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Drugs targeting the renin-angiotensin-aldosterone system. Author(s): Zaman MA, Oparil S, Calhoun DA. Source: Nature Reviews. Drug Discovery. 2002 August; 1(8): 621-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402502
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Dynamic interactions between integrative physiology and molecular medicine: the key to understand the mechanism of action of aldosterone in the kidney. Author(s): Halperin ML, Kamel KS. Source: Canadian Journal of Physiology and Pharmacology. 2000 August; 78(8): 587-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10958158
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Early aldosterone up-regulated genes: new pathways for renal disease? Author(s): Kellner M, Peiter A, Hafner M, Feuring M, Christ M, Wehling M, Falkenstein E, Losel R. Source: Kidney International. 2003 October; 64(4): 1199-207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969137
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Effect of beta blockade (carvedilol or metoprolol) on activation of the reninangiotensin-aldosterone system and natriuretic peptides in chronic heart failure. Author(s): Fung JW, Yu CM, Yip G, Chan S, Yandle TG, Richards AM, Nicholls MG, Sanderson JE. Source: The American Journal of Cardiology. 2003 August 15; 92(4): 406-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12914870
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Effect of combined AT1 receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1. Author(s): Sawathiparnich P, Murphey LJ, Kumar S, Vaughan DE, Brown NJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3867-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915681
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Effect of indomethacin on amniotic fluid prostaglandin and aldosterone levels in a fetus with Bartter syndrome. Author(s): Amsalem H, Valsky DV, Yagel S, Celnikier DH, Anteby EY. Source: Prenatal Diagnosis. 2003 May; 23(5): 431-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749044
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Effect of nasal CPAP treatment on plasma volume, aldosterone and 24-h blood pressure in obstructive sleep apnoea. Author(s): Saarelainen S, Hasan J, Siitonen S, Seppala E. Source: Journal of Sleep Research. 1996 September; 5(3): 181-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8956208
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Effect of progesterone on aldosterone secretion in rats. Author(s): Braley LM, Menachery AI, Yao T, Mortensen RM, Williams GH. Source: Endocrinology. 1996 November; 137(11): 4773-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8895346
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Effect of the renin-angiotensin-aldosterone system on the cardiac interstitium in heart failure. Author(s): Wilke A, Funck R, Rupp H, Brilla CG. Source: Basic Research in Cardiology. 1996; 91 Suppl 2: 79-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8957549
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Effects of canrenoate potassium, an aldosterone antagonist on portal hemodynamics in patients with compensated liver cirrhosis. Author(s): Koda M, Murawaki Y, Kawasaki H, Ikawa S. Source: Hepatogastroenterology. 1996 July-August; 43(10): 887-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8884309
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Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Author(s): Oelkers WK. Source: Steroids. 1996 April; 61(4): 166-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732994
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Effects of metoclopramide and tropisetron on aldosterone secretion possibly due to agonism and antagonism at the 5-HT4 receptor. Author(s): Sommers DK, Snyman JR, van Wyk M. Source: European Journal of Clinical Pharmacology. 1996; 50(5): 371-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8839658
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Effects of the intravenous magnesium administration on aldosterone and atrial natriuretic factor plasma concentrations. Author(s): Corica F, Allegra A, Ientile R, Buemi M, Cucinotta G, Bonanzinga S, Ceruso D. Source: Nephron. 1996; 73(4): 739-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8856296
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Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Author(s): White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, Weber MA. Source: Hypertension. 2003 May; 41(5): 1021-6. Epub 2003 April 07. Erratum In: Hypertension. 2003 December; 42(6): E20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682082
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Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin. Author(s): Auberson M, Hoffmann-Pochon N, Vandewalle A, Kellenberger S, Schild L. Source: American Journal of Physiology. Renal Physiology. 2003 September; 285(3): F459-71. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759227
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Eplerenone, a new selective aldosterone blocker. Author(s): McMahon EG. Source: Current Pharmaceutical Design. 2003; 9(13): 1065-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678858
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Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. Author(s): Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Source: The New England Journal of Medicine. 2003 April 3; 348(14): 1309-21. Epub 2003 March 31. Erratum In: N Engl J Med. 2003 May 29; 348(22): 2271. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668699
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Eplerenone: a selective aldosterone blocker. Author(s): Stier CT Jr. Source: Cardiovasc Drug Rev. 2003 Fall; 21(3): 169-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12931252
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Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. Author(s): Moore TD, Nawarskas JJ, Anderson JR. Source: Heart Disease. 2003 September-October; 5(5): 354-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14503934
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Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Author(s): Goodfriend TL, Ball DL, Egan BM, Campbell WB, Nithipatikom K. Source: Hypertension. 2004 February; 43(2): 358-63. Epub 2004 January 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718355
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Essential hypertension and left ventricular hypertrophy in cardiovascular disease: beyond overactivity of the renin-angiotensin-aldosterone-sodium system. Author(s): Buikema H. Source: Journal of Hypertension. 2003 February; 21(2): 265-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569254
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Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype. Author(s): Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Cabrini G, Bonizzato A, Graziani M, Anker SD, Coats AJ, Zardini P. Source: Journal of the American College of Cardiology. 2001 June 1; 37(7): 1808-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401115
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Falsely elevated plasma aldosterone concentration by direct radioimmunoassay in chronic renal failure. Author(s): Koshida H, Miyamori I, Miyazaki R, Tofuku Y, Takeda R. Source: The Journal of Laboratory and Clinical Medicine. 1989 September; 114(3): 294300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2769019
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Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. Author(s): Torpy DJ, Gordon RD, Lin JP, Huggard PR, Taymans SE, Stowasser M, Chrousos GP, Stratakis CA. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 September; 83(9): 3214-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9745430
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Familial salivary gland insensitivity to aldosterone: a variant of pseudohypoaldosteronism. Author(s): Sanderson IR, Carter EP, Dillon MJ, Oberholzer VG, Savage MO. Source: Hormone Research. 1989; 32(4): 145-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2625324
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Fast effects of aldosterone on electrolytes in human lymphocytes are mediated by the sodium-proton-exchanger of the cell membrane. Author(s): Wehling M, Kasmayr J, Theisen K. Source: Biochemical and Biophysical Research Communications. 1989 November 15; 164(3): 961-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2556129
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Fatty acids may regulate aldosterone secretion and mediate some of insulin's effects on blood pressure. Author(s): Goodfriend TL, Ball DL, Elliott ME, Chabhi A, Duong T, Raff H, Schneider EG, Brown RD, Weinbergers MH. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1993 January; 48(1): 4350. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8424122
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Fenoldopam: effect on aldosterone secretion. Author(s): Dupont AG, Vanderniepen P, Volckaert A, Smitz J, Vansteirteghem AC, Six RO. Source: British Journal of Clinical Pharmacology. 1986 February; 21(2): 243-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2869776
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Fibrosis in hypertensive heart disease: role of the renin-angiotensin-aldosterone system. Author(s): Gonzalez A, Lopez B, Diez J. Source: The Medical Clinics of North America. 2004 January; 88(1): 83-97. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14871052
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Final steps of aldosterone biosynthesis: molecular solution of a physiological problem. Author(s): Muller J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1993 April; 45(1-3): 153-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8481340
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Flight influence on the plasma level of renin-angiotensin-aldosterone system and atrial natriuretic peptide. Author(s): Wang YM, Sheng DY. Source: Aviation, Space, and Environmental Medicine. 1990 November; 61(11): 999-1001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2147850
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Flow cytometric analysis of deoxyribonucleic acid ploidy in benign and malignant aldosterone-producing neoplasms of the adrenal gland. Author(s): Rainwater LM, Young WF Jr, Farrow GM, Grant CS, van Heerden JA, Lieber MM. Source: Surg Gynecol Obstet. 1989 June; 168(6): 491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2727877
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Fluid replacement beverages and maintenance of plasma volume during exercise: role of aldosterone and vasopressin. Author(s): Criswell D, Renshler K, Powers SK, Tulley R, Cicale M, Wheeler K. Source: European Journal of Applied Physiology and Occupational Physiology. 1992; 65(5): 445-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1425651
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Fluid-electrolyte shift and renin-aldosterone responses to exercise under hypoxia. Author(s): Bouissou P, Peronnet F, Brisson G, Helie R, Ledoux M. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1987 July; 19(7): 331-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3305278
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Formation of 18-deoxy-19-noraldosterone by a human aldosterone-producing adenoma. Author(s): Takeda Y, Iki K, Miyamori I, Takeda R. Source: Steroids. 1993 June; 58(6): 282-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8212075
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Functional derangements in the regulation of aldosterone secretion in hypertension. Author(s): Williams GH, Hollenberg NK. Source: Hypertension. 1991 November; 18(5 Suppl): Iii143-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1937678
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Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Author(s): Coulter CL, Jaffe RB. Source: Endocrinology. 1998 December; 139(12): 5144-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9832454
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Functional relevance of aldosterone for the determination of left ventricular mass. Author(s): Delles C, Schmidt BM, Muller HJ, Oehmer S, Klingbeil AU, Schmieder RE. Source: The American Journal of Cardiology. 2003 February 1; 91(3): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12565086
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Functionally active catalytic domain is essential for guanylyl cyclase-linked receptor mediated inhibition of human aldosterone synthesis. Author(s): Olson LJ, Ho BY, Cashdollar LW, Drewett JG. Source: Molecular Pharmacology. 1998 November; 54(5): 761-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9804611
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Gamma 2-MSH increases during graded exercise in healthy subjects: comparison with plasma catecholamines, neuropeptides, aldosterone and renin activity. Author(s): Valdemarsson S, Andersson D, Bengtsson A, Bogren M, Edvinsson L, Ekman R. Source: Clinical Physiology (Oxford, England). 1990 July; 10(4): 321-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2203597
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Gender specific association of aldosterone synthase gene polymorphism with renal survival in patients with IgA nephropathy. Author(s): Song J, Narita I, Goto S, Saito N, Omori K, Sato F, Ajiro J, Saga D, Kondo D, Sakatsume M, Gejyo F. Source: Journal of Medical Genetics. 2003 May; 40(5): 372-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746403
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Gene polymorphisms of the renin-angiotensin-aldosterone system and essential arterial hypertension in childhood. Author(s): Petrovic D, Bidovec M, Peterlin B. Source: Folia Biol (Krakow). 2002; 50(1-2): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597535
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Generalized unresponsiveness to mineralocorticoid hormones: familial recessive pseudohypoaldosteronism due to aldosterone-receptor deficiency. Author(s): Bosson D, Kuhnle U, Mees N, Ramet J, Vamos E, Vertongen F, Wolter R, Armanini D. Source: Acta Endocrinol Suppl (Copenh). 1986; 279: 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2946135
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Genetic analysis of aldosterone synthase in patients with idiopathic hyperaldosteronism. Author(s): Takeda Y, Furukawa K, Inaba S, Miyamori I, Mabuchi H. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 May; 84(5): 1633-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10323392
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Genetic analysis of the cytochrome P-450c17alpha (CYP17) and aldosterone synthase (CYP11B2) in Japanese patients with 17alpha-hydroxylase deficiency. Author(s): Takeda Y, Yoneda T, Demura M, Furukawa K, Koshida H, Miyamori I, Mabuchi H. Source: Clinical Endocrinology. 2001 June; 54(6): 751-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422109
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Genetic basis of cardiovascular disease--the renin-angiotensin-aldosterone system as a paradigm. Author(s): Padmanabhan N, Padmanabhan S, Connell JM. Source: J Renin Angiotensin Aldosterone Syst. 2000 December; 1(4): 316-24. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967817
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Genetic determination of plasma aldosterone levels in essential hypertension. Author(s): Pojoga L, Gautier S, Blanc H, Guyene TT, Poirier O, Cambien F, Benetos A. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1998 July; 11(7): 856-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9683048
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Genetic influences on the urinary excretion of aldosterone in children. Author(s): Manatunga AK, Reister TK, Miller JZ, Pratt JH. Source: Hypertension. 1992 February; 19(2): 192-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1737654
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Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Author(s): Ortlepp JR, Vosberg HP, Reith S, Ohme F, Mahon NG, Schroder D, Klues HG, Hanrath P, McKenna WJ. Source: Heart (British Cardiac Society). 2002 March; 87(3): 270-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11847170
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Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Author(s): Lovati E, Richard A, Frey BM, Frey FJ, Ferrari P. Source: Kidney International. 2001 July; 60(1): 46-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422735
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Genetic recombination as a cause of inherited disorders of aldosterone and cortisol biosynthesis and a contributor to genetic variation in blood pressure. Author(s): Pascoe L, Curnow KM. Source: Steroids. 1995 January; 60(1): 22-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792811
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Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension. Author(s): Ambrosius WT, Bloem LJ, Zhou L, Rebhun JF, Snyder PM, Wagner MA, Guo C, Pratt JH. Source: Hypertension. 1999 October; 34(4 Pt 1): 631-7. Erratum In: Hypertension 2003 January; 41(1): 1E. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10523338
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Genetic variation in aldosterone synthase predicts plasma glucose levels. Author(s): Ranade K, Wu KD, Risch N, Olivier M, Pei D, Hsiao CF, Chuang LM, Ho LT, Jorgenson E, Pesich R, Chen YD, Dzau V, Lin A, Olshen RA, Curb D, Cox DR, Botstein D. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 November 6; 98(23): 13219-24. Epub 2001 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687612
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Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. Author(s): Paillard F, Chansel D, Brand E, Benetos A, Thomas F, Czekalski S, Ardaillou R, Soubrier F. Source: Hypertension. 1999 September; 34(3): 423-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10489388
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Glomerular hyperfiltration in insulin-dependent diabetes mellitus: no evidence for enhanced activity of the renin-angiotensin-aldosterone system. Author(s): Carvalho-Braga D, Almeida R, Azevedo M, Amaral I, Medina J, Hargreaves M. Source: J Diabet Complications. 1991 April-September; 5(2-3): 126-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1770018
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Growth hormone activates renin-aldosterone system in children with idiopathic short stature and in a pseudohypoaldosteronism patient with a mutation in epithelial sodium channel alpha subunit. Author(s): Hanukoglu A, Belutserkovsky O, Phillip M. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 April; 77(1): 49-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358674
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Guanine nucleotide-dependent carboxymethylation: a pathway for aldosterone modulation of apical Na+ permeability in epithelia. Author(s): Sariban-Sohraby S, Fisher RS. Source: Kidney International. 1995 October; 48(4): 965-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8569106
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Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension. Author(s): Kumar NN, Benjafield AV, Lin RC, Wang WY, Stowasser M, Morris BJ. Source: Journal of Hypertension. 2003 July; 21(7): 1331-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12817181
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Haplotypes of aldosterone synthase (CYP11B2) gene in the general population of Japan: the Ohasama study. Author(s): Matsubara M, Omori F, Fujita S, Metoki H, Kikuya M, Fujiwara T, Araki T, Imai Y. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2001 November; 23(8): 603-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728005
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Heparin-induced aldosterone suppression and hyperkalemia. Author(s): Oster JR, Singer I, Fishman LM. Source: The American Journal of Medicine. 1995 June; 98(6): 575-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7778574
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Hepatorenal disorders: role of the renin-angiotensin-aldosterone system. Author(s): Bernardi M, Trevisani F, Gasbarrini A, Gasbarrini G. Source: Seminars in Liver Disease. 1994 February; 14(1): 23-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8016659
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Hereditary defect in biosynthesis of aldosterone: aldosterone synthase deficiency 1964-1997. Author(s): Peter M, Fawaz L, Drop SL, Visser HK, Sippell WG. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 November; 82(11): 3525-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9360501
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Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. Author(s): Zennaro MC, Le Menuet D, Viengchareun S, Walker F, Ricquier D, Lombes M. Source: The Journal of Clinical Investigation. 1998 March 15; 101(6): 1254-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9502766
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High and non-suppressible plasma renin activity in a patient with aldosterone producing adenoma: pathophysiologic and diagnostic implications. Author(s): Shyong Tai E, Eng PH. Source: Journal of Human Hypertension. 1999 January; 13(1): 75-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9928756
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High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to renin ratio as a screening test among Italian hypertensives. Author(s): Rossi E, Regolisti G, Negro A, Sani C, Davoli S, Perazzoli F. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 October; 15(10 Pt 1): 896-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372677
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How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Author(s): MacFadyen RJ, Lee AF, Morton JJ, Pringle SD, Struthers AD. Source: Heart (British Cardiac Society). 1999 July; 82(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10377310
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Human adrenal cortex and aldosterone secreting adenomas express both 11betahydroxysteroid dehydrogenase type 1 and type 2 genes. Author(s): Albertin G, Tortorella C, Malendowicz LK, Aragona F, Neri G, Nussdorfer GG. Source: International Journal of Molecular Medicine. 2002 May; 9(5): 495-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956655
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Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3. Author(s): Taymans SE, Pack S, Pak E, Torpy DJ, Zhuang Z, Stratakis CA. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 March; 83(3): 10336. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9506770
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Human epidermal growth factor receptor-1 expression renders Chinese hamster ovary cells sensitive to alternative aldosterone signaling. Author(s): Krug AW, Schuster C, Gassner B, Freudinger R, Mildenberger S, Troppmair J, Gekle M. Source: The Journal of Biological Chemistry. 2002 November 29; 277(48): 45892-7. Epub 2002 September 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12244120
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Human NCI-H295 adrenocortical carcinoma cells: a model for angiotensin-IIresponsive aldosterone secretion. Author(s): Bird IM, Hanley NA, Word RA, Mathis JM, McCarthy JL, Mason JI, Rainey WE. Source: Endocrinology. 1993 October; 133(4): 1555-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8404594
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Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase. Author(s): Kenouch S, Lombes M, Delahaye F, Eugene E, Bonvalet JP, Farman N. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 November; 79(5): 1334-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7962326
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Hyperkalemia, congestive heart failure, and aldosterone receptor antagonism. Author(s): Sica DA, Gehr TW, Yancy C. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 224-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937359
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Hypertension and primary hyperparathyroidism: the role of adrenergic and reninangiotensin-aldosterone systems. Author(s): Gennari C, Nami R, Gonnelli S. Source: Mineral and Electrolyte Metabolism. 1995; 21(1-3): 77-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7565468
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Hypertension due to coexisting pheochromocytoma and aldosterone-producing adrenal cortical adenoma. Author(s): Miyazawa K, Kigoshi T, Nakano S, Kobayashi Y, Suzuki K, Tsugawa R, Uchida K. Source: American Journal of Nephrology. 1998; 18(6): 547-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9845834
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Hypertension, angiotensin II, aldosterone, and race. Author(s): Ben-Yehuda O. Source: Journal of the American College of Cardiology. 2003 April 2; 41(7): 1156-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679216
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Hypothesis: aldosterone is synthesized by an alternative pathway during severe sodium depletion. 'A new wine in an old bottle'. Author(s): Boon WC, McDougall JG, Coghlan JP. Source: Clinical and Experimental Pharmacology & Physiology. 1998 May; 25(5): 369-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9612665
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Hypoxia modulates rapid effects of aldosterone on oxidative metabolism in human calf muscle. Author(s): Christ M, Zange J, Janson CP, Muller K, Kuklinski P, Schmidt BM, Tillmann HC, Gerzer R, Wehling M. Source: J Endocrinol Invest. 2001 September; 24(8): 587-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11686541
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Identification and role of aldosterone receptors in the cardiovascular system. Author(s): Lombes M, Farman N, Bonvalet JP, Zennaro MC. Source: Annales D'endocrinologie. 2000 February; 61(1): 41-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10790591
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Idiopathic hyperaldosteronism: analysis of aldosterone synthase gene. Author(s): Miyamori I, Inaba S, Hatakeyama H, Taniguchi N, Takeda Y. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2000 June; 54 Suppl 1: 77S-79S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914997
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Impact of aldosterone on left ventricular structure and function in young normotensive and mildly hypertensive subjects. Author(s): Schlaich MP, Schobel HP, Hilgers K, Schmieder RE. Source: The American Journal of Cardiology. 2000 May 15; 85(10): 1199-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10802001
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Impact of aldosterone on vascular pathophysiology. Author(s): Struthers AD. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 January-February; 8(1): 1822. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821624
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Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension. Author(s): Tiago AD, Badenhorst D, Nkeh B, Candy GP, Brooksbank R, Sareli P, Libhaber E, Samani NJ, Woodiwiss AJ, Norton GR. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 December; 16(12): 1006-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14643573
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In vitro release of aldosterone and cortisol in human adrenal adenomas correlates to mRNA expression of steroidogenic enzymes for genes CYP11B2 and CYP17. Author(s): Enberg U, Farnebo LO, Wedell A, Grondal S, Thoren M, Grimelius L, Kjellman M, Backdahl M, Hamberger B. Source: World Journal of Surgery. 2001 July; 25(7): 957-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11572038
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Increase of aldosterone secretion following acute haloperidol administration: possible clinical implications. Author(s): Liberini P, Nisoli E, Missale C, Turrina C, Frisoni GB, Caruso R, Spano PF. Source: International Clinical Psychopharmacology. 1996 March; 11(1): 67-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732319
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Increased aldosterone levels in acute mountain sickness at Capanna Regina Margherita. Author(s): Angelini C, Cogo A, Madrigale G, Pecchio O, Posani L. Source: Wilderness Environ Med. 1997 November; 8(4): 247-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990171
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Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin-angiotensin-aldosterone system. Author(s): Ekman B, Ohman PK, Arnqvist HJ, Lindstrom T, Nystrom FH. Source: Clinical Endocrinology. 2002 October; 57(4): 473-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354129
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Induction of cardiac fibrosis by aldosterone. Author(s): Lijnen P, Petrov V. Source: Journal of Molecular and Cellular Cardiology. 2000 June; 32(6): 865-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10888242
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Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism. Author(s): Seifarth C, Trenkel S, Schobel H, Hahn EG, Hensen J. Source: Clinical Endocrinology. 2002 October; 57(4): 457-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354127
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Influence of plasma aldosterone on left ventricular geometry and diastolic function in treated essential hypertension. Author(s): Iwashima Y, Horio T, Kuroda S, Takishita S, Kawano Y. Source: Hypertens Res. 2002 January; 25(1): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11924725
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Inhibition of the renin-angiotensin-aldosterone system in heart failure: new insights from basic clinical research. Author(s): Cleland JG, Morgan K. Source: Current Opinion in Cardiology. 1996 May; 11(3): 252-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835867
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Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and loss of the insertion allele in aldosterone-producing adenoma. Author(s): Tunny TJ, Xu L, Richardson KA, Stowasser M, Gartside M, Gordon RD. Source: Journal of Human Hypertension. 1996 December; 10(12): 827-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9140790
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Insulin, renin-aldosterone system and blood pressure in obese people. Author(s): Andronico G, Cottone S, Mangano MT, Ferraro-Mortellaro R, Baiardi G, Grassi N, Ferrara L, Mule G, Cerasola G. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2001 February; 25(2): 239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11410826
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Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance. Author(s): Meune C, Mourad JJ, Bergmann JF, Spaulding C. Source: J Renin Angiotensin Aldosterone Syst. 2003 September; 4(3): 149-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608518
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Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study. Author(s): Russo P, Siani A, Venezia A, Iacone R, Russo O, Barba G, D'Elia L, Cappuccio FP, Strazzullo P. Source: Journal of Hypertension. 2002 September; 20(9): 1785-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195120
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Interaction of rapid nongenomic cardiovascular aldosterone effects with the adrenergic system. Author(s): Schmidt BM, Georgens AC, Martin N, Tillmann HC, Feuring M, Christ M, Wehling M. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 761-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158043
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Inverse relation between aldosterone and venous capacitance in chronically treated congestive heart failure. Author(s): Rietzschel E, Duprez DA, De Buyzere ML, Clement DL. Source: The American Journal of Cardiology. 2000 April 15; 85(8): 977-80. Erratum In: Am J Cardiol 2000 August 15; 86(4): 484. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10760338
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Isolated adrenocorticotropin deficiency presenting with impaired renin-angiotensinaldosterone system and suppressed parathyroid hormone-vitamin D axis. Author(s): Saito T, Tojo K, Yamamoto H, Hosoya T, Tajima N. Source: Intern Med. 2002 July; 41(7): 561-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12132525
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Jejunal permeability to water and electrolytes in patients with chronic intrahepatic hypertension: evidence for a role of aldosterone. Author(s): Duclos B, Bories P, Mathieu-Daude JC, Michel H. Source: Gut. 1991 June; 32(6): 640-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2060871
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Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction. Author(s): Hautanen A, Toivanen P, Manttari M, Tenkanen L, Kupari M, Manninen V, Kayes KM, Rosenfeld S, White PC. Source: Circulation. 1999 November 30; 100(22): 2213-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577993
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K(+) depletion and the progression of hypertensive disease or heart failure. The pathogenic role of diuretic-induced aldosterone secretion. Author(s): Laragh JH, Sealey JE. Source: Hypertension. 2001 February; 37(2 Part 2): 806-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11230377
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Kaliuretic peptide and long acting natriuretic peptide as well as atrial natriuretic factor inhibit aldosterone secretion. Author(s): Vesely DL, Chiou S, Douglass MA, McCormick MT, Rodriguez-Paz G, Schocken DD. Source: The Journal of Endocrinology. 1995 September; 146(3): 373-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7595132
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Kaliuretic response to aldosterone: influence of the content of potassium in the diet. Author(s): Vasuvattakul S, Quaggin SE, Scheich AM, Bayoumi A, Goguen JM, CheemaDhadli S, Halperin ML. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1993 February; 21(2): 152-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8430675
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Karyotypic abnormalities in benign adrenocortical tumors producing aldosterone. Author(s): Gordon RD, Stowasser M, Martin N, Epping A, Conic S, Klemm SA, Tunny TJ, Rutherford JC. Source: Cancer Genetics and Cytogenetics. 1993 July 1; 68(1): 78-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8330287
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Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. Author(s): Schunkert H, Hengstenberg C, Holmer SR, Broeckel U, Luchner A, Muscholl MW, Kurzinger S, Doring A, Hense HW, Riegger GA. Source: Circulation. 1999 May 4; 99(17): 2255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226090
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Lack of correlation between human serum angiotensin converting enzyme activity and the renin-angiotensin-aldosterone system. Author(s): Pedraza-Chaverri J, Herrero B, Ibarra-Rubio ME, Cruz C, Tapia E, Pena JC. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1990 September; 190(1-2): 105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2170063
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Lack of enhanced responsiveness of plasma 18-hydroxycorticosterone and aldosterone to adrenocorticotropin as well as to angiotensin-II during moderate sodium depletion in type II diabetic subjects with normoreninemia. Author(s): Kigoshi T, Iwasaki R, Kaneko M, Nakano S, Azukizawa S, Uchida K, Morimoto S. Source: The Journal of Clinical Endocrinology and Metabolism. 1991 June; 72(6): 1200-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1851181
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Lack of evidence for the interaction between renin-angiotensin-aldosterone system and endothelin in vivo. Author(s): Widimsky J Jr, Dvorakova J, Hladovec J, Kopecka J. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 1996; 45(3): 241-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9200216
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Lack of rapid aldosterone effects on forearm resistance vasculature in health. Author(s): Gunaruwan P, Schmitt M, Taylor J, Lee L, Struthers A, Frenneaux M. Source: J Renin Angiotensin Aldosterone Syst. 2002 June; 3(2): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12228853
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Laparoscopic adrenal-sparing surgery for primary hyperaldosteronism due to aldosterone-producing adenoma. Author(s): Kok KY, Yapp SK. Source: Surgical Endoscopy. 2002 January; 16(1): 108-11. Epub 2001 October 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961617
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Laparoscopic partial adrenalectomy in patients with aldosterone-producing adenomas: indications, technique, and results. Author(s): Jeschke K, Janetschek G, Peschel R, Schellander L, Bartsch G, Henning K. Source: Urology. 2003 January; 61(1): 69-72; Discussion 72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559268
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Late steps of aldosterone biosynthesis: sheep are not rats. Author(s): Boon WC, Coghlan JP, McDougall JG. Source: Clin Exp Pharmacol Physiol Suppl. 1998 November; 25: S21-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9809188
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Left ventricular hypertrophy and remodelling of resistance arteries: the role of activation of the renin-angiotensin-aldosterone system in hypertension. Author(s): Hayoz D. Source: Journal of Hypertension. 2002 July; 20(7): 1295-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131524
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Left ventricular hypertrophy in asymptomatic essential hypertension: its relationship with aldosterone and the increase in sodium-proton exchanger activity. Author(s): Navarro-Lopez F, Coca A, Pare JC, De La Sierra A, Bosch X, Urbano Marquez A. Source: European Heart Journal. 1993 November; 14 Suppl J: 38-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8281961
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Left ventricular mass and geometry before and after etiologic treatment in renovascular hypertension, aldosterone-producing adenoma, and pheochromocytoma. Author(s): Denolle T, Chatellier G, Julien J, Battaglia C, Luo P, Plouin PF. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1993 November; 6(11 Pt 1): 907-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8305163
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Local renin-angiotensin system is involved in K+-induced aldosterone secretion from human adrenocortical NCI-H295 cells. Author(s): Hilbers U, Peters J, Bornstein SR, Correa FM, Johren O, Saavedra JM, EhrhartBornstein M. Source: Hypertension. 1999 April; 33(4): 1025-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10205242
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Localization of the endothelin system in aldosterone-producing adenomas. Author(s): Egidy G, Baviera E, Ciuffo G, Corvol P, Pinet F. Source: Hypertension. 2001 November; 38(5): 1137-42. Erratum In: Hypertension 2002 January; 39(1): E9-E11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711511
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Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia. Author(s): August P, Lenz T, Ales KL, Druzin ML, Edersheim TG, Hutson JM, Muller FB, Laragh JH, Sealey JE. Source: American Journal of Obstetrics and Gynecology. 1990 November; 163(5 Pt 1): 1612-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146881
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Long-PCR of the ANP gene and PCR-SSCP analysis of the proximal promoter region of the ANP gene in patients with aldosterone producing adenoma. Author(s): Tunny TJ, Richardson KA, Moriarty CC, Klemm SA, Stowasser M, Gordon RD. Source: Biochemical and Biophysical Research Communications. 1995 October 4; 215(1): 172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7575587
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Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Author(s): Malmqvist K, Ohman KP, Lind L, Nystrom F, Kahan T. Source: Journal of Cardiovascular Pharmacology. 2003 December; 42(6): 719-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639093
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Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients. Author(s): Ichikawa S, Takayama Y. Source: Hypertens Res. 2001 November; 24(6): 641-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768722
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Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. Author(s): Burgess ED, Lacourciere Y, Ruilope-Urioste LM, Oparil S, Kleiman JH, Krause S, Roniker B, Maurath C. Source: Clinical Therapeutics. 2003 September; 25(9): 2388-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604739
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Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans. Author(s): Gandhi SK, Ryder DH, Brown NJ. Source: Hypertension. 1996 December; 28(6): 961-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8952583
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Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus: effects of RAAS stimulation. Author(s): Luik PT, Kerstens MN, Hoogenberg K, Navis GJ, Dullaart RP. Source: European Journal of Clinical Investigation. 2003 September; 33(9): 787-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925038
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Masked hyperprolactinemia in a case of aldosterone-producing adrenal adenoma. Author(s): Oki Y, Yagi T, Yoshimi T. Source: Annals of Internal Medicine. 1995 December 1; 123(11): 893-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7486481
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Measured haplotype analysis of the aldosterone synthase gene and heart size. Author(s): Mayosi BM, Keavney B, Watkins H, Farrall M. Source: European Journal of Human Genetics : Ejhg. 2003 May; 11(5): 395-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734545
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Micromolar concentrations of steroids and of aldosterone antagonists inhibit the outwardly rectifying chloride channel with different kinetics. Author(s): Rabe A, Fromter E. Source: Pflugers Archiv : European Journal of Physiology. 2000 March; 439(5): 559-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10764215
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Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system. Author(s): Young MJ, Funder JW. Source: Journal of Hypertension. 2002 August; 20(8): 1465-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172301
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Modulators of the renin-angiotensin-aldosterone system and cough in childhood. Author(s): Donati-Genet P, Bianchetti MG. Source: Pediatric Nephrology (Berlin, Germany). 1996 August; 10(4): 545-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8865265
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Molecular basis of salt sensitivity in human hypertension. Evaluation of reninangiotensin-aldosterone system gene polymorphisms. Author(s): Poch E, Gonzalez D, Giner V, Bragulat E, Coca A, de La Sierra A. Source: Hypertension. 2001 November; 38(5): 1204-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711524
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Molecular mechanisms of myocardial remodeling. The role of aldosterone. Author(s): Delcayre C, Swynghedauw B. Source: Journal of Molecular and Cellular Cardiology. 2002 December; 34(12): 1577-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505056
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More evidence on blocking the renin-angiotensin-aldosterone system in cardiovascular disease and the long-term treatment of hypertension: data from recent clinical trials (CHARM, EUROPA, ValHEFT, HOPE-TOO and SYST-EUR2). Author(s): Lip GY, Beevers DG. Source: Journal of Human Hypertension. 2003 November; 17(11): 747-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578913
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More hope for heart failure. Findings suggest expanded use of aldosterone-blockers. Author(s): Aaronson K. Source: Health News. 2003 May; 9(5): 4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739453
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Morphometric analysis, at electron microscope level, combined with hormone assay of nonfunctioning adrenocortical adenomas: comparison with aldosterone-producing adenomas. Author(s): Hirano D, Okada Y, Ishida H, Takimoto Y, Okada K, Jike T. Source: Medical Electron Microscopy : Official Journal of the Clinical Electron Microscopy Society of Japan. 2001 December; 34(4): 240-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956997
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Mutation T318M in the CYP11B2 gene encoding P450c11AS (aldosterone synthase) causes corticosterone methyl oxidase II deficiency. Author(s): Zhang G, Rodriguez H, Fardella CE, Harris DA, Miller WL. Source: American Journal of Human Genetics. 1995 November; 57(5): 1037-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7485152
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Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. Author(s): Kozakova M, Buralli S, Palombo C, Bernini G, Moretti A, Favilla S, Taddei S, Salvetti A. Source: Hypertension. 2003 February; 41(2): 230-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574087
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New biology of aldosterone, and experimental studies on the selective aldosterone blocker eplerenone. Author(s): Funder JW. Source: American Heart Journal. 2002 November; 144(5 Suppl): S8-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422135
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New insights into the role of aldosterone in cardiorenal disease and the clinical implications. Introduction. Author(s): Pitt B. Source: American Heart Journal. 2002 November; 144(5 Suppl): S1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422133
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Non-genomic actions of aldosterone: mechanisms and consequences in kidney cells. Author(s): Boldyreff B, Wehling M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 September; 18(9): 1693-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937210
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Non-genomic aldosterone action: from the cell membrane to human physiology. Author(s): Losel R, Feuring M, Wehling M. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 167-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650713
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Nongenomic effects of aldosterone on human renal cells. Author(s): Koppel H, Christ M, Yard BA, Bar PC, van der Woude FJ, Wehling M. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 1297302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629122
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Nongenomic effects of aldosterone on phosphocreatine levels in human calf muscle during recovery from exercise. Author(s): Zange J, Muller K, Gerzer R, Sippel K, Wehling M. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 December; 81(12): 4296-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8954030
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Nongenomic effects of aldosterone: cellular aspects and clinical implications. Author(s): Losel RM, Feuring M, Falkenstein E, Wehling M. Source: Steroids. 2002 May; 67(6): 493-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11960626
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Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells. Author(s): Bowley KA, Morton MJ, Hunter M, Sandle GI. Source: Gut. 2003 June; 52(6): 854-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740342
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Novel action of activin and bone morphogenetic protein in regulating aldosterone production by human adrenocortical cells. Author(s): Suzuki J, Otsuka F, Inagaki K, Takeda M, Ogura T, Makino H. Source: Endocrinology. 2004 February; 145(2): 639-49. Epub 2003 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14592955
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Novel natriuretic peptide receptor/guanylyl cyclase A-selective agonist inhibits angiotensin II- and forskolin-evoked aldosterone synthesis in a human zona glomerulosa cell line. Author(s): Olson LJ, Lowe DG, Drewett JG. Source: Molecular Pharmacology. 1996 August; 50(2): 430-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8700153
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Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone. Author(s): Follenius M, Krieger J, Krauth MO, Sforza F, Brandenberger G. Source: Sleep. 1991 June; 14(3): 211-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1896722
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On the prenatal diagnosis of congenital adrenal hyperplasia (CAH) by measurement of amniotic fluid 17-alpha-hydroxyprogesterone, aldosterone and cortisol. Author(s): Grankvist K, Backstrom BT, Gustavsson G, Holmgren G. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1989; 68(1): 71-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2801032
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On the viability of a physiological system. Regulation of potassium by aldosterone. Author(s): Auberlet JM, Vielle B, Chauvet GA. Source: Comptes Rendus De L'academie Des Sciences. Serie Iii, Sciences De La Vie. 1998 October; 321(10): 797-803. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9835017
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Ontogeny of aldosterone glucuronidation by the human newborn. Author(s): Leslie GI. Source: Early Human Development. 1986 December; 14(3-4): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3803264
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Opioid peptides do not modulate atrial natriuretic peptide or aldosterone release under basal conditions in man. Author(s): Borges F, Anderson JV, Volta C, Perry L, Drury PL, Bloom SR, Besser GM, Grossman A. Source: The Journal of Endocrinology. 1988 February; 116(2): 313-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2965206
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Opposite associations of circulating aldosterone and atrial natriuretic peptide with left ventricular diastolic function in essential hypertension. Author(s): Fagard RH, Lijnen PJ, Petrov VV. Source: Journal of Human Hypertension. 1998 March; 12(3): 195-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579770
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Optimisation of total urinary aldosterone estimation: comparison with other laboratory methods for assessment of mineralocorticoid status. Author(s): Cunningham SK, Sequeira SJ, Chambers J, Heffernan A, McKenna TJ. Source: J Steroid Biochem. 1988 July; 31(1): 125-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3398526
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Ouabain is a potent inhibitor of aldosterone secretion and angiotensin action in the human adrenal. Author(s): Antonipillai I, Schick K, Horton R. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 June; 81(6): 2335-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8964873
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Ouabain-inhibiting activity of aldosterone antagonists. Author(s): Semplicini A, Serena L, Valle R, Ceolotto G, Felice M, Fontebasso A, Pessina AC. Source: Steroids. 1995 January; 60(1): 110-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792794
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Pathophysiological aspects of the renin-angiotensin-aldosterone system in acute myocardial infarction. Author(s): Dargie HJ, Byrne J. Source: Journal of Cardiovascular Risk. 1995 October; 2(5): 389-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749265
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PCR-SSCP analysis of the promoter region of the renin gene in patients with aldosterone-producing adenomas. Author(s): Ballantine DM, Klemm SA, Tunny TJ, Stowasser M, Gordon RD. Source: Clinical and Experimental Pharmacology & Physiology. 1996 June-July; 23(6-7): 584-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8800592
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Pituitary adenylate-cyclase activating peptide enhances aldosterone secretion of human adrenal gland: evidence for an indirect mechanism, probably involving the local release of catecholamines. Author(s): Neri G, Andreis PG, Prayer-Galetti T, Rossi GP, Malendowicz LK, Nussdorfer GG. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 January; 81(1): 16973. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8550747
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Plasma endothelin-1 levels in patients with aldosterone-producing adenoma and pheochromocytoma. Author(s): Letizia C, De Toma G, Cerci S, Scuro L, De Ciocchis A, D'Ambrosio C, Massa R, Cavallaro A, Scavo D. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1996 October; 18(7): 921-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8886476
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Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells. Author(s): Li LA, Wang PW, Chang LW. Source: Toxicology and Applied Pharmacology. 2004 February 15; 195(1): 92-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962509
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Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide. Author(s): Wu KD, Liao TS, Chen YM, Lai MK, Chen SJ, Su CT, Chu TS, Chang CC, Hsieh BS. Source: J Formos Med Assoc. 2001 September; 100(9): 598-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11695274
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Prevalence and role of a raised aldosterone to renin ratio in the diagnosis of primary aldosteronism: a debate on the scientific logic of the use of the ratio in practice. Author(s): Padfield PL. Source: Clinical Endocrinology. 2003 October; 59(4): 422-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510902
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Primary aldosteronism with bilateral multiple aldosterone-producing adrenal adenomas. Author(s): Matsuda A, Beniko M, Ikota A, Yamazaki M, Koizumi S, Mizumoto H, Watanabe T, Matsuya K, Kunita H, Mashio Y, Sasano H. Source: Intern Med. 1996 December; 35(12): 970-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9030997
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Primary aldosteronism, diagnosed by the aldosterone to renin ratio, is a common cause of hypertension. Author(s): Lim PO, MacDonald TM. Source: Clinical Endocrinology. 2003 October; 59(4): 427-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510903
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Pseudohypoaldosteronism: family studies to identify asymptomatic carriers by stimulation of the renin-aldosterone system. Author(s): Kuhnle U, Hinkel GK, Hubl W, Reichelt T. Source: Hormone Research. 1996; 46(3): 124-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8894667
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Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosteroneproducing adenomas. Author(s): Fallo F, Pezzi V, Barzon L, Mulatero P, Veglio F, Sonino N, Mathis JM. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 December; 147(6): 795-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457455
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Rapid inhibition of vasoconstriction in renal afferent arterioles by aldosterone. Author(s): Uhrenholt TR, Schjerning J, Hansen PB, Norregaard R, Jensen BL, Sorensen GL, Skott O. Source: Circulation Research. 2003 December 12; 93(12): 1258-66. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615288
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Rapid nongenomic aldosterone effects in the human forearm? Author(s): Schmitt M, Gunaruwan P, Frenneaux MP. Source: Hypertension. 2004 January; 43(1): E1; Author Reply E2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696601
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Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. Author(s): Takeda Y, Miyamori I, Yoneda T, Hatakeyama H, Inaba S, Furukawa K, Mabuchi H, Takeda R. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 August; 81(8): 2797-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8768832
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Relationship between plasma aldosterone and left ventricular structure and function in patients with essential hypertension. Author(s): Lazurova I, Valocik G, Zabranska B, Fraenkel E. Source: Bratisl Lek Listy. 2003; 104(6): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594353
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Remikiren (Ro 42-5892)--an orally active renin inhibitor in essential hypertension. Effects on blood pressure and the renin-angiotensin-aldosterone system. Author(s): Himmelmann A, Bergbrant A, Svensson A, Hansson L, Aurell M. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1996 June; 9(6): 517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8783774
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Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Author(s): Goodfriend TL, Calhoun DA. Source: Hypertension. 2004 March; 43(3): 518-24. Epub 2004 January 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732721
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Responses of plasma norepinephrine and renin-angiotensin-aldosterone system to dynamic exercise in patients with congestive heart failure. Author(s): Kato M, Kinugawa T, Omodani H, Osaki S, Ahmmed GU, Ogino K, Hisatome I, Miyakoda H, Thames MD. Source: Journal of Cardiac Failure. 1996 June; 2(2): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8798111
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Role of calmodulin-dependent protein kinase II in the acute stimulation of aldosterone production. Author(s): Pezzi V, Clark BJ, Ando S, Stocco DM, Rainey WE. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1996 July; 58(4): 41724. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8903426
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Role of epinephrine-induced hypokalemia in the regulation of renin and aldosterone in humans. Author(s): Kolloch RE, Kruse HJ, Friedrich R, Ruppert M, Overlack A, Stumpe KO. Source: The Journal of Laboratory and Clinical Medicine. 1996 January; 127(1): 50-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8592096
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Role of intracardiac renin-angiotensin-aldosterone system in extracellular matrix remodeling. Author(s): Lijnen PJ, Petrov VV. Source: Methods Find Exp Clin Pharmacol. 2003 September; 25(7): 541-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571285
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Screening for primary aldosteronism: implications of an increased plasma aldosterone/renin ratio. Author(s): Schwartz GL, Chapman AB, Boerwinkle E, Kisabeth RM, Turner ST. Source: Clinical Chemistry. 2002 November; 48(11): 1919-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406976
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Screening for primary aldosteronism--normal ranges for aldosterone and renin in three South African population groups. Author(s): Rayner BL, Myers JE, Opie LH, Trinder YA, Davidson JS. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2001 July; 91(7): 594-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11544978
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Selective aldosterone blockade with eplerenone in patients with congestive heart failure. Author(s): Salam AM. Source: Expert Opinion on Investigational Drugs. 2003 August; 12(8): 1423-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882627
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Selective hypoaldosteronism due to combined defects of the conversion from inactive renin to active renin and the aldosterone biosynthesis from corticosterone. Author(s): Muto S, Akai Y, Ono S, Kusano E, Asano Y. Source: Nephron. 2001 July; 88(3): 247-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11423756
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Serial plasma concentrations of atrial natriuretic peptide, plasma renin activity, aldosterone, and antidiuretic hormone in neonates on extracorporeal membrane oxygenation. Author(s): Semmekrot BA, Pesman GJ, Span PN, Sweep CG, van Heijst AF, Monnens LA, van de Bor M, Tanke RB, van der Staak FH. Source: Asaio Journal (American Society for Artificial Internal Organs : 1992). 2002 January-February; 48(1): 26-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11820219
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SGK1: aldosterone-induced relay of Na+ transport regulation in distal kidney nephron cells. Author(s): Verrey F, Loffing J, Zecevic M, Heitzmann D, Staub O. Source: Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2003; 13(1): 21-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649599
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Short-term aldosterone action on Na,K-ATPase surface expression: role of aldosterone-induced SGK1? Author(s): Verrey F, Summa V, Heitzmann D, Mordasini D, Vandewalle A, Feraille E, Zecevic M. Source: Annals of the New York Academy of Sciences. 2003 April; 986: 554-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763889
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Should the aldosterone-receptor antagonist - eplerenone - be used after acute myocardial infarction with left ventricular dysfunction? Author(s): Doggrell S. Source: Expert Opinion on Pharmacotherapy. 2003 September; 4(9): 1605-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943490
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Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial. Author(s): Cohn JN, Anand IS, Latini R, Masson S, Chiang YT, Glazer R; Valsartan Heart Failure Trial Investigators. Source: Circulation. 2003 September 16; 108(11): 1306-9. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12939207
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Symptoms and the distress they cause: comparison of an aldosterone antagonist and a calcium channel blocking agent in patients with systolic hypertension. Author(s): Hollenberg NK, Williams GH, Anderson R, Akhras KS, Bittman RM, Krause SL. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1543-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860576
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Tetralogy of Fallot repair results in activation of the renin-angiotensin-aldosterone system. Author(s): Mainwaring RD, Lamberti JJ, Moore JW, Billman GF, Carter TL, Nelson JC. Source: European Heart Journal. 1996 September; 17(9): 1421-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8880028
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The adrenal renin-angiotensin system: a local hormonal regulator of aldosterone production. Author(s): Mulrow PJ, Franco-Saenz R. Source: Journal of Hypertension. 1996 February; 14(2): 173-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8728293
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The amino acid substitutions Ser288Gly and Val320Ala convert the cortisol producing enzyme, CYP11B1, into an aldosterone producing enzyme. Author(s): Curnow KM, Mulatero P, Emeric-Blanchouin N, Aupetit-Faisant B, Corvol P, Pascoe L. Source: Nature Structural Biology. 1997 January; 4(1): 32-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8989319
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The atrial natriuretic peptide-renin-aldosterone system in hepatorenal syndrome. Author(s): Pasqualetti P, Casale R. Source: Riv Eur Sci Med Farmacol. 1996 July-August; 18(4): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9177611
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The cardiac renin-angiotensin-aldosterone system and hypertensive cardiac hypertrophy. Author(s): Raman VK, Lee YA, Lindpaintner K. Source: The American Journal of Cardiology. 1995 November 2; 76(13): 18D-23D. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7495212
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The H295R human adrenocortical cell line contains functional atrial natriuretic peptide receptors that inhibit aldosterone biosynthesis. Author(s): Bodart V, Rainey WE, Fournier A, Ong H, De Lean A. Source: Molecular and Cellular Endocrinology. 1996 April 19; 118(1-2): 137-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8735599
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The renin-angiotensin-aldosterone system and cardiac ischaemia. Author(s): Ikram H. Source: Heart (British Cardiac Society). 1996 November; 76(3 Suppl 3): 60-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8983666
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The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure. Author(s): Brilla CG, Rupp H, Funck R, Maisch B. Source: European Heart Journal. 1995 December; 16 Suppl O: 107-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8682074
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The renin-angiotensin-aldosterone system and the cardiac natriuretic peptides. Author(s): Richards AM. Source: Heart (British Cardiac Society). 1996 November; 76(3 Suppl 3): 36-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8983665
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The renin-angiotensin-aldosterone system: focus on its distinct role in arterial hypertension and its various inhibitors as a therapeutic strategy to effectively lower blood pressure. Author(s): Soldner A, Spahn-Langguth H, Mutschler E. Source: Pharmazie. 1996 November; 51(11): 783-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8985974
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Ultrasonography in the diagnosis of aldosterone-producing adenoma: is it useful? Author(s): Yamakita N, Yasuda K, Miura K. Source: Intern Med. 1992 May; 31(5): 589-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1504419
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Understanding how aldosterone increases sodium transport. Author(s): Stokes JB. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 October; 36(4): 866-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11007694
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Unequal crossing-over between aldosterone synthase and 11beta-hydroxylase genes causes congenital adrenal hyperplasia. Author(s): Hampf M, Dao NT, Hoan NT, Bernhardt R. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 September; 86(9): 4445-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549691
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Unilateral adrenal hypersecretion of both aldosterone and cortisol in two first cousins with a syndrome of mineralocorticoid excess but without signs of hypercortisolism. Author(s): Ferri C, Falaschi P, Gualdi G, Coassin S, Carlomagno A, De Siati L, Bonavita MS, Balsano F. Source: Endocrine Research. 1994 May; 20(2): 165-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8055832
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Unlike heparin, low-molecular weight heparin does not suppress aldosterone production. Author(s): Marcelli JM, Lalau JD, Abourachid H, Quiret JC, Quichaud J. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1989 July; 21(7): 402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2550344
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Unorthodox sites and modes of aldosterone action. Author(s): Oberleithner H. Source: News in Physiological Sciences : an International Journal of Physiology Produced Jointly by the International Union of Physiological Sciences and the American Physiological Society. 2004 April; 19: 51-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15016902
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Urinary excretion of 19-noraldosterone, 18, 19-dihydroxycorticosterone and 18hydroxy-19-norcorticosterone in patients with aldosterone-producing adenoma or idiopathic hyperaldosteronism. Author(s): Takeda Y, Miyamori I, Iki K, Takeda R, Vecsei P. Source: Acta Endocrinol (Copenh). 1992 June; 126(6): 484-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1642080
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Urinary excretion of aldosterone, arginine vasopressin and cortisol in premature infants with maximum renal acid stimulation. Author(s): Kalhoff H, Rascher W, Diekmann L, Stock GJ, Manz F. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 May; 84(5): 490-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7633141
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Urinary vasopressin and aldosterone and plasma volume during a saturation dive to 450 m. Author(s): Claybaugh JR, Goldinger JM, Moon RE, Fawcett TA, Exposito AG, Hong SK, Holthaus J, Bennett PB. Source: Undersea Biomed Res. 1992 July; 19(4): 295-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1353929
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Use of plasma aldosterone concentration-to-plasma renin activity ratio as a screening test for primary aldosteronism. A systematic review of the literature. Author(s): Montori VM, Young WF Jr. Source: Endocrinology and Metabolism Clinics of North America. 2002 September; 31(3): 619-32, Xi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12227124
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Validity of the aldosterone-renin ratio used to screen for primary aldosteronism. Author(s): Montori VM, Schwartz GL, Chapman AB, Boerwinkle E, Turner ST. Source: Mayo Clinic Proceedings. 2001 September; 76(9): 877-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560297
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Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism. Author(s): Tanabe A, Naruse M, Takagi S, Tsuchiya K, Imaki T, Takano K. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2489-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788844
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Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio. Author(s): Lim PO, Macdonald TM, Holloway C, Friel E, Anderson NH, Dow E, Jung RT, Davies E, Fraser R, Connell JM. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 September; 87(9): 4398-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12213905
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Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells. Author(s): Hatakeyama H, Miyamori I, Fujita T, Takeda Y, Takeda R, Yamamoto H. Source: The Journal of Biological Chemistry. 1994 September 30; 269(39): 24316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7929089
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Vascular aldosterone. Biosynthesis and a link to angiotension II-induced hypertrophy of vascular smooth muscle cells. Author(s): Gomez-Sanchez EP. Source: J Endocrinol Invest. 1995 July-August; 18(7): 580-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9221278
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Vascular and cardiac actions of aldosterone and spironolactone. Author(s): Zannad F. Source: Zeitschrift Fur Kardiologie. 1991; 80 Suppl 7: 103-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1792814
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Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension. The Research Committee of Disorders of Adrenal Hormones in Japan. Author(s): Takeda R, Matsubara T, Miyamori I, Hatakeyama H, Morise T. Source: J Endocrinol Invest. 1995 May; 18(5): 370-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7594226
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Verapamil sustained-release in renal parenchymal hypertension: effect on blood pressure, kidney function, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, and lipoproteins. Author(s): Eiskjaer H, Pedersen EB, Rasmussen LM, Jespersen B. Source: Journal of Cardiovascular Pharmacology. 1989; 13 Suppl 4: S17-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2475677
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Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Author(s): Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Source: Obesity Research. 1999 July; 7(4): 355-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10440591
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Volume regulation of human lymphocytes by aldosterone in isotonic media. Author(s): Wehling M, Kuhls S, Armanini D. Source: The American Journal of Physiology. 1989 August; 257(2 Pt 1): E170-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2764099
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Water immersion induced alterations of plasma vasopressin levels and activity of the renin-angiotensin-aldosterone system in noninflammatory acute renal failure and end-stage renal failure. Author(s): Kokot F, Grzeszczak W, Zukowska-Szczechowska E, Wiecek A. Source: International Urology and Nephrology. 1990; 22(3): 285-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2210986
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Water immersion-induced alterations of plasma atrial natriuretic peptide level and its relationship to the renin-angiotensin-aldosterone system and vasopressin secretion in acute and chronic renal failure. Author(s): Kokot F, Grzeszczak W, Zukowska-Szczechowska E, Wiecek A. Source: Clinical Nephrology. 1989 May; 31(5): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525441
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Water immersion-induced alterations of plasma atrial natriuretic peptide, plasma renin activity, plasma aldosterone, and vasopressin in kidney transplant recipients. Author(s): Kokot F, Grzeszczak W, Wiecek A, Zukowska-Szczechowska E, Kusmierski S, Szkodny A. Source: Transplantation Proceedings. 1989 February; 21(1 Pt 2): 2052-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2523598
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Water-immersion-induced alterations of atrial natriuretic peptide, plasma renin activity, aldosterone and vasopressin in diabetic patients. Author(s): Kokot F, Dulawa J, Bar A, Klin M, Grzeszczak W, Darocha Z. Source: Contrib Nephrol. 1989; 73: 102-10; Discussion 110-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2532119
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Yohimbine and aldosterone responsiveness to angiotensin II or corticotrophin in normal subjects. Author(s): Lucchini E, Kressebuch H, Beretta-Piccoli C. Source: Clin Exp Hypertens A. 1989; 11(4): 649-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2551545
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Zona fasciculata-like cells determine the response of plasma aldosterone to metoclopramide and aldosterone synthase messenger ribonucleic acid level in aldosterone-producing adenoma. Author(s): Wu KD, Chen YM, Chu JS, Hung KY, Hsieh TS, Hsieh BS. Source: The Journal of Clinical Endocrinology and Metabolism. 1995 March; 80(3): 783-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7883831
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Zona fasciculata-like histotype and aldosterone response to upright posture are not related in aldosterone-producing adenomas. Author(s): Fallo F, Barzon L, Biasi F, Altavilla G, Boscaro M, Sonino N. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 1998; 106(1): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9516064
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CHAPTER 2. NUTRITION AND ALDOSTERONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and aldosterone.
Finding Nutrition Studies on Aldosterone 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 “aldosterone” (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 “aldosterone” (or a synonym): •
Age-related impairment of aldosterone secretion in zona glomerulosa cells of ovariectomized rats. Author(s): Department of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, R.O.C. Source: Kau, M M Chen, J J Wang, S W Cho, W L Wang, P S J-Investig-Med. 1999 September; 47(8): 425-32 1081-5589
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Angiotensin receptor blockers and aldosterone antagonists in chronic heart failure. Author(s): Division of Cardiology, Department of Medicine, University of Florida Health Science Center, Jacksonville, Jacksonville, Florida, USA.
[email protected] Source: Miller, A B Srivastava, P Cardiol-Clin. 2001 May; 19(2): 195-202, v 0733-8651
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Calcitonin gene-related peptide (CGRP), acting via CGRP type 1 receptors, inhibits potassium-stimulated aldosterone secretion and enhances basal catecholamine secretion from rat adrenal gland. Author(s): Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, Via Gabelli 65, I-35121 Padua, Italy. Source: Tortorella, C Macchi, C Forneris, M Nussdorfer, G G Int-J-Mol-Med. 2001 September; 8(3): 261-4 1107-3756
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Defective suppression of the aldosterone biosynthesis during stroke permissive diet in the stroke-prone phenotype of the spontaneously hypertensive rat. Author(s): Istituto Neurologico Mediterraneo Neuromed, Camerelle Pozzilli, Italy. Source: Enea, I De Paolis, P Porcellini, A Piras, O Savoia, C Russo, R Giliberti, R Gigante, B Rubattu, S Conte, G Ganten, D Volpe, M Basic-Res-Cardiol. 2000 April; 95(2): 84-92 0300-8428
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Eplerenone: a selective aldosterone receptor antagonist (SARA). Author(s): Pharmacia, 4901 Searle Parkway, Skokie, IL 60077, USA.
[email protected] Source: Delyani, J A Rocha, R Cook, C S Tobert, D S Levin, S Roniker, B Workman, D L Sing, Y L Whelihan, B Cardiovasc-Drug-Revolume 2001 Fall; 19(3): 185-200 0897-5957
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Evidence for a paracrine role of adrenomedullin in the physiological resetting of aldosterone secretion by rat adrenal zona glomerulosa. Author(s): Department of Human Anatomy and Physiology (Section of Anatomy), University of Padua, I-35121, Padua, Italy. Source: Albertin, G Malendowicz, L K Tortorella, C Mazzocchi, G Nussdorfer, G G Peptides. 2000 March; 21(3): 413-7 0196-9781
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Guanylin: a novel regulatory peptide possibly involved in the control of Ca2+dependent agonist-stimulated aldosterone secretion in rats. Author(s): Department of Anatomy, University of Padua, I-35121 Padua, Italy. Source: Andreis, P G Tortorella, C Malendowicz, L K Rebuffat, P Mazzocchi, G Neri, G Nussdorfer, G G Int-J-Mol-Med. 1999 January; 3(1): 59-62 1107-3756
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In vivo regulation of enzymes controlling aldosterone synthesis in pregnant rats. Author(s): Research Center Ste-Justine Hospital and Department of ObstetricsGynecology, Universite de Montreal, Quebec, Canada. Source: Brochu, M Roy Clavel, E Picard, S St Louis, J Endocr-Res. 1998 Aug-November; 24(3-4): 575-9 0743-5800
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Inhibitory effect of evodiamine on aldosterone release by Zona glomerulosa cells in male rats. Author(s): Department of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC. Source: Hung, P H Lin, L C Wang, G J Chen, C F Wang, P S Chin-J-Physiol. 2001 June 30; 44(2): 53-7 0304-4920
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Insulin prevents glucose induced inhibition of angiotensin II-stimulated aldosterone secretion. Author(s): Department of Physiology and Biophysics, University of Tennessee, Memphis. Source: Schneider, E G Robinson, T V Horm-Metab-Res. 1991 May; 23(5): 205-8 00185043
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Morphological adaptations to induced changes in transepithelial sodium transport in chicken lower intestine (coprodeum): a study of resalination, aldosterone stimulation, and epithelial turnover. Author(s): Department of Anatomy and Physiology, The Royal Veterinary and Agricultural University, Bulowsvej 13, DK-1870 Frederiksberg C, Denmark.
[email protected] Source: Elbrond, V S Skadhauge, E Thomsen, L Dantzer, V Cell-Tissue-Res. 1998 June; 292(3): 543-52 0302-766X
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Rapid effects of aldosterone on sodium-hydrogen exchange in isolated colonic crypts. Author(s): Department of Surgery, Yale University, 310 Cedar Street, BML 265, New Haven, CT 06510-8026, USA. Source: Winter, D C Schneider, M F O'Sullivan, G C Harvey, B J Geibel, J P J-MembrBiol. 1999 July 1; 170(1): 17-26 0022-2631
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Rat model for investigating ACTH-independent angiotensin-induced aldosterone secretion. Author(s): Divisions of Endocrinology and Metabolism and Nephrology and Hypertension, Georgetown University, Washington DC, 20007, USA.
[email protected] Source: Roesch, D M Tian, Y Verbalis, J G Sandberg, K J-Renin-AngiotensinAldosterone-Syst. 2000 March; 1(1): 36-9 1470-3203
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Regulation of aldosterone biosynthesis. Physiological and clinical aspects. Author(s): Dept. of Medicine, University Hospital, Zurich, Switzerland. Source: Muller, J Monogr-Endocrinol. 1987; 291-364 0077-1015
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Stimulatory effects of hyperprolactinemia on aldosterone secretion in ovariectomized rats. Author(s): National Taipei College of Nursing, Taiwan, Republic of China. Source: Kau, Mei Mei Chang, Ling Ling Kan, Shu Fen Ho, Low Tone Wang, Paulus S JInvestig-Med. 2002 March; 50(2): 101-9 1081-5589
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The effect of sodium balance on sweat sodium secretion and plasma aldosterone concentration. Author(s): Institute of Naval Medicine, Gosport, Hampshire, UK. Source: Allsopp, A J Sutherland, R Wood, P Wootton, S A Eur-J-Appl-Physiol-OccupPhysiol. 1998 November; 78(6): 516-21 0301-5548
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to aldosterone; 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: •
Food and Diet Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND ALDOSTERONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to aldosterone. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to aldosterone and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “aldosterone” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to aldosterone: •
A direct radioimmunoassay for aldosterone in unextracted serum and plasma. Author(s): Lee TP, Tan CH. Source: Clinical Chemistry. 1981 December; 27(12): 2019-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6796290
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A role for src tyrosine kinase in regulating adrenal aldosterone production. Author(s): Sirianni R, Sirianni R, Carr BR, Pezzi V, Rainey WE. Source: Journal of Molecular Endocrinology. 2001 June; 26(3): 207-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11357057
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Aldosterone and dopamine receptors in the kidney: sites for pharmacologic manipulation of renal function. Author(s): Adam WR.
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Source: Kidney International. 1980 November; 18(5): 623-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6257964 •
Aldosterone and insulin stimulate amiloride-sensitive sodium transport in A6 cells by additive mechanisms. Author(s): Record RD, Johnson M, Lee S, Blazer-Yost BL. Source: The American Journal of Physiology. 1996 October; 271(4 Pt 1): C1079-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8897813
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Aldosterone and sodium-potassium-dependent ATPase activity of rat kidney membranes. Author(s): Landon EJ, Jazab N, Forte L. Source: The American Journal of Physiology. 1966 October; 211(4): 1050-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4224513
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Aldosterone and the Gerson diet -- a speculation. Author(s): McCarty MF. Source: Medical Hypotheses. 1981 May; 7(5): 591-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7278723
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Aldosterone receptor antagonism normalizes vascular function in liquorice-induced hypertension. Author(s): Quaschning T, Ruschitzka F, Shaw S, Luscher TF. Source: Hypertension. 2001 February; 37(2 Part 2): 801-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11230376
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Altered renin and aldosterone excretion in patients treated for metastatic germ cell tumours. Author(s): Bosl GJ, Leitner SP, Atlas SA, Sealey JE, Preibisz JJ, Scheiner E. Source: International Journal of Andrology. 1987 February; 10(1): 353-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2438226
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Angiotensin I-converting enzyme levels and renin-aldosterone axis recovery after cessation of chronic licorice ingestion. Author(s): Megia A, Herranz L, Martin-Almendra MA, Martinez I. Source: Nephron. 1993; 65(2): 329-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8247207
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Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells. Author(s): Douglas J, Aguilera G, Kondo T, Catt K.
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Source: Endocrinology. 1978 March; 102(3): 685-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=217598 •
Blood pressure, plasma renin activity and aldosterone concentrations in vegans and omnivore controls. Author(s): Sanders TA, Key TJ. Source: Hum Nutr Appl Nutr. 1987 June; 41(3): 204-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3305428
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Ca antagonists do not alter aldosterone secretion during established Na depletion. Author(s): Johnson EI, McDougall JG, Coghlan JP, Denton DA, Hardy KJ, Scoggins BA, Wright RD. Source: The American Journal of Physiology. 1985 June; 248(6 Pt 1): E676-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2408478
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Calcium modulation of the renin-aldosterone axis. Author(s): Porter L, Conlin PR, Scott J, Brown EM, El-Hajj Fuleihan G. Source: J Endocrinol Invest. 1999 February; 22(2): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10195378
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Characterization of the rat colonic aldosterone receptor and its activation process. Author(s): Schulman G, Miller-Diener A, Litwack G, Bastl CP. Source: The Journal of Biological Chemistry. 1986 September 15; 261(26): 12102-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2943734
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Circadian rhythm of ANP, aldosterone and PRA in normotensive IUGR. Author(s): Maggioni C, Lucini D, Antinozzi R, Pagani M. Source: Journal of Hypertension. 2001 September; 19(9): 1659-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11564987
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Comparative studies on the mineralo-corticoid action of aldosterone and carbenoxolone sodium in the adrenalectomized rat. Author(s): Porter GA, Rhodes C, Sacra P. Source: Pharmacology. 1974; 12(4-5): 224-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4449886
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Dietary potassium supplementation and sodium restriction stimulate aldosterone synthase but not 11 beta-hydroxylase P-450 messenger ribonucleic acid accumulation in rat adrenals and require angiotensin II production. Author(s): Tremblay A, Parker KL, Lehoux JG.
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Source: Endocrinology. 1992 June; 130(6): 3152-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1597135 •
Diuretics and hypokalaemia: aldosterone antagonists or potassium supplementation? Author(s): Demanet JC. Source: Acta Clin Belg. 1974; 29(3): 176-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4842207
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Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR. Author(s): Engler MM, Engler MB, Goodfriend TL, Ball DL, Yu Z, Su P, Kroetz DL. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1999 May; 221(1): 32-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10320629
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Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes. Author(s): Calo LA, Zaghetto F, Pagnin E, Davis PA, De Mozzi P, Sartorato P, Martire G, Fiore C, Armanini D. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 April; 89(4): 1973-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15070972
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Effect of angiotensin II and of an angiotensin II analogue (Sar1-Ile8-angiotensin II) on blood pressure, plasma aldosterone and plasma renin activity in the dog. Author(s): Beckerhoff R, Uhlschmid G, Vetter W, Armbruster H, Nussberger J, Reck G, Schmied U, Siegenthaler W. Source: Clin Sci Mol Med Suppl. 1975 June; 2: 41S-44S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1077788
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Effect of eating liquorice on the renin-angiotensin aldosterone axis in normal subjects. Author(s): Epstein MT, Espiner EA, Donald RA, Hughes H. Source: British Medical Journal. 1977 February 19; 1(6059): 488-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=837172
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Effect of high-dose aldosterone infusions on renal electrolyte excretion in patients with renal insufficiency. Author(s): Hene RJ, Koomans HA, Boer P, Dorhout Mees EJ. Source: American Journal of Nephrology. 1987; 7(1): 33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3578372
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Effect of physiological levels of atrial natriuretic peptide on hormone secretion: inhibition of angiotensin-induced aldosterone secretion and renin release in normal
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man. Author(s): Cuneo RC, Espiner EA, Nicholls MG, Yandle TG, Livesey JH. Source: The Journal of Clinical Endocrinology and Metabolism. 1987 October; 65(4): 76572. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2821056 •
Effect of weight reduction on the renin-aldosterone axis. Author(s): Vaswani AN. Source: Journal of the American College of Nutrition. 1985; 4(2): 225-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3894477
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Effects of acupuncture on the plasma atrial natriuretic peptide. Aldosterone and renin activity in man. Author(s): Lee HS, Song JC, Kim KS. Source: Acupuncture & Electro-Therapeutics Research. 1991; 16(3-4): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1685619
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Effects of aldosterone and vasopressin on electrolytes of toad bladder epithelial cells. Author(s): Lipton P, Edelman IS. Source: The American Journal of Physiology. 1971 September; 221(3): 733-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5570330
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Effects of in vitro aldosterone on the rabbit cortical collecting tubule. Author(s): Wingo CS, Kokko JP, Jacobson HR. Source: Kidney International. 1985 July; 28(1): 51-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2413237
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Effects of prolactin on aldosterone secretion in rat zona glomerulosa cells. Author(s): Kau MM, Lo MJ, Tsai SC, Chen JJ, Pu HF, Chien EJ, Chang LL, Wang PS. Source: Journal of Cellular Biochemistry. 1999 February 1; 72(2): 286-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10022511
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Effects of san-huang-hsieh-hsin-tang on sympathetic activity, plasma renin, and plasma aldosterone. Author(s): Chen HC, Hsieh MT. Source: Clinical Therapeutics. 1985; 7(5): 600-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3902239
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Further observations of aldosterone response in barnacle muscle fibers. Author(s): Tallitsch RB.
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Source: The American Journal of Physiology. 1983 September; 245(3): E230-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6614162 •
Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. Author(s): Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R. Source: The Journal of Biological Chemistry. 1992 December 5; 267(34): 24248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1360010
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Hypertension with aldosterone excess. Author(s): Brown JJ, Fraser R, Lever AF, Robertson JI. Source: British Medical Journal. 1972 May 13; 2(810): 391-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4554158
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Imbalancing of hemic calcium, magnesium, potassium, and sodium by rations and by perenteral injections of ethylenediaminetetraacetate dipotassium salt, potassium chloride, and aldosterone inhibitor. Comparison of cattle held at 2,745 and at 1,372 meters elevation. Author(s): Blake JT, Bailey DE, Lu YS, Fisher EJ, Abaza R, Call JW. Source: Am J Vet Res. 1969 February; 30(2): 171-81. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4984985
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Involvement of tyrosine kinase in citrate-stimulated aldosterone production in bovine glomerulosa cells. Author(s): Kigoshi T, Imaizumi N, Yoshida J, Nakagawa A, Nakano S, Nishio M, Uchida K. Source: American Journal of Physiology. Endocrinology and Metabolism. 2000 July; 279(1): E140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10893333
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Liquorice toxicity and the renin-angiotensin-aldosterone axis in man. Author(s): Epstein MT, Espiner EA, Donald RA, Hughes H. Source: British Medical Journal. 1977 January 22; 1(6055): 209-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=832078
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Metabolic studies, aldosterone secretion rate, and plasma renin after carbenoxolone sodium. Author(s): Baron JH, Nabarro JD, Slater JD, Tuffley R. Source: British Medical Journal. 1969 June 28; 2(660): 793-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5784614
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Novel membrane receptors for aldosterone in human lymphocytes: a 50 kDa protein on SDS-PAGE. Author(s): Eisen C, Meyer C, Christ M, Theisen K, Wehling M. Source: Cell Mol Biol (Noisy-Le-Grand). 1994 May; 40(3): 351-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7920179
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Occupancy of aldosterone binding sites in rat kidney cytosol. Author(s): Warnock DG, Edelman IS. Source: Molecular and Cellular Endocrinology. 1978 November; 12(2): 221-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=215476
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On the biochemical mechanism of action of aldosterone. Author(s): Edelman IS, Fimognari GM. Source: Recent Progress in Hormone Research. 1968; 24: 1-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4235849
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Oxidative response to aldosterone of pyridine nucleotide in rat kidney in situ. Author(s): Ogata E, Nishiki K, Kugai N, Kishikawa T. Source: The American Journal of Physiology. 1977 April; 232(4): E401-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=192085
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Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation. Author(s): Golf SW, Happel O, Graef V, Seim KE. Source: J Clin Chem Clin Biochem. 1984 November; 22(11): 717-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6527092
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Plasma renin activity, angiotensin II, and aldosterone during the hypnotic suggestion of running. Author(s): Kosunen KJ, Kuoppasalmi K, Naveri H, Rehunen S, Narvanen S, Adlercreutz H. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1977 April; 37(2): 99-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=616045
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Potentiating effects of calcium chelators on basal and stimulated aldosterone production by bovine adrenal glomerulosa cells in vitro. Author(s): Kigoshi T, Okamoto H, Ishii T, Ito T, Hotta F, Kitazawa M, Nishizawa M, Nakano S, Morimoto S, Uchida K. Source: Endocrine Journal. 1997 April; 44(2): 335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9228471
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Rapid aldosterone effects on tyrosine phosphorylation in vascular smooth muscle cells. Author(s): Manegold JC, Falkenstein E, Wehling M, Christ M. Source: Cell Mol Biol (Noisy-Le-Grand). 1999 September; 45(6): 805-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541477
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Rectal potential difference in the diagnosis of aldosterone excess. Author(s): Beevers DG, Morton JJ, Tree M, Young J. Source: Gut. 1975 January; 16(1): 36-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=237802
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Renal function, body fluid volumes, renin, aldosterone, and noradrenaline during treatment of hypertension with pindolol. Author(s): Wilcox CS, Lewis PS, Peart WS, Sever PS, Osikowska BA, Suddle SA, Bluhm MM, Veall N, Lancaster R. Source: Journal of Cardiovascular Pharmacology. 1981 May-June; 3(3): 598-611. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6168840
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Renin aldosterone system and potassium levels in chronic lead intoxication. Author(s): Gonzalez JJ, Werk EE Jr, Thrasher K, Behar R, Loadholt CB. Source: Southern Medical Journal. 1979 April; 72(4): 433-6, 440. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=107594
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Renin, aldosterone and glucagon in the natriuresis of fasting. Author(s): Spark RF, Arky RA, Boulter PR, Saudek CD, O'Brian JT. Source: The New England Journal of Medicine. 1975 June 19; 292(25): 1335-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=165411
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Renin, cortisol, and aldosterone during transcendental meditation. Author(s): Michaels RR, Parra J, McCann DS, Vander AJ. Source: Psychosomatic Medicine. 1979 February; 41(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=373002
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Renin-aldosterone axis in normoalbuminuric insulin-dependent diabetes mellitus patients with glomerular hyperfiltration. Author(s): de Azevedo MJ, Ramos OL, Gross JL. Source: Diabetes Research and Clinical Practice. 1995 March; 27(3): 205-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7555603
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Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells. Author(s): Bello-Reuss E, Ernest S, Holland OB, Hellmich MR.
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Source: American Journal of Physiology. Cell Physiology. 2000 June; 278(6): C1256-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10837354 •
Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells. Author(s): Nadler JL, Natarajan R, Stern N. Source: The Journal of Clinical Investigation. 1987 December; 80(6): 1763-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2824567
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Stimulatory effects of hyperprolactinemia on aldosterone secretion in ovariectomized rats. Author(s): Kau MM, Chang LL, Kan SF, Ho LT, Wang PS. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2002 March; 50(2): 101-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11928939
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The effect of an intravenous infusion of aldosterone upon magnesium metabolism in the sheep. Author(s): Charlton JA, Armstrong DG. Source: Q J Exp Physiol. 1989 May; 74(3): 329-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2748795
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The effect of carbenoxolone on the subcellular distribution of ( 3 H) aldosterone in rat kidney. Author(s): Humphrey MJ, Lindup E, Parke DV, Chakraborty J. Source: The Biochemical Journal. 1972 November; 130(2): 87P-88P. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4664613
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The effect of prolactin on human aldosterone-producing adenomas in vitro. Author(s): Carroll JE, Campanile CP, Goodfriend TL. Source: The Journal of Clinical Endocrinology and Metabolism. 1982 April; 54(4): 689-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6277980
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The nature of the increased sensitivity to injected GTP of the sodium efflux in barnacle muscle fibers pre-exposed to aldosterone. Author(s): Bittar EE, Chiang L, Nwoga J. Source: Comp Biochem Physiol A. 1984; 77(1): 117-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6141020
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The participation of cAMP and protein kinase C in the regulation of aldosterone biosynthesis by potassium. Author(s): Pushkarev VM, Mikosha AS.
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Source: Biomed Sci. 1991; 2(2): 135-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1663396 •
The pharmacology and clinical use of rauwolfia, hydralazine, thiazides, and aldosterone antagonists in arterial hypertension. Author(s): Hollander W, Wilkins RW. Source: Progress in Cardiovascular Diseases. 1966 January; 8(4): 291-318. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5902963
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The renin-angiotensin-aldosterone system in primary and secondary hypertension. Author(s): del Greco F, Huang CM, Quintanilla A, Krumlovsky F, Roxe DM, Santhanam S. Source: Ann Clin Lab Sci. 1981 November-December; 11(6): 497-505. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6119955
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The role of tyrosine kinases in capacitative calcium influx-mediated aldosterone production in bovine adrenal zona glomerulosa cells. Author(s): Aptel HB, Burnay MM, Rossier MF, Capponi AM. Source: The Journal of Endocrinology. 1999 October; 163(1): 131-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10495415
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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The following is a specific Web list relating to aldosterone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Adrenal Extract Source: Healthnotes, Inc.; www.healthnotes.com Borago Alternative names: Borage; Borago officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Indomethacin Source: Healthnotes, Inc.; www.healthnotes.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON ALDOSTERONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to aldosterone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “aldosterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on aldosterone, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Aldosterone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to aldosterone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Effects of aldosterone on the metabolism of heart muscle by Liew, Choong-Chin; ADVDEG from University of Toronto (Canada), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK01492
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Extracellular matrix remodeling: Potential mechanisms by which aldosterone blockade improves ventricular remodeling and function post myocardial infarction by Le, Jenny Wenyi; MSc from University of Toronto (Canada), 2003, 103 pages http://wwwlib.umi.com/dissertations/fullcit/MQ84434
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Influence of caffeine ingestion on fluid-electrolyte regulating hormones, aldosterone and arginine vasopressin, and physiological responses at rest and during an exercise heat tolerance test by Roti, Melissa Leigh Wehnert; PhD from The University of Connecticut, 2003, 85 pages http://wwwlib.umi.com/dissertations/fullcit/3104095
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Studies on aldosterone and its relations to Na,K - ATPase by Knox, William H; PhD from University of Toronto (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK27898
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON ALDOSTERONE 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 “aldosterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on aldosterone, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Aldosterone By performing a patent search focusing on aldosterone, 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 aldosterone: •
18-Substituted pregn-4-ene-3,20-diones Inventor(s): Johnston; J. O'Neal (Cincinnati, OH), Metcalf; Brian W. (Mason, OH) Assignee(s): Merrell Dow Pharmaceuticals Inc. (Cincinnati, OH) Patent Number: 4,293,548 Date filed: September 2, 1980 Abstract: Progesterone derivatives having a vinylidene or a 1-alkynyl substituent at the 18-position and further optionally hydroxylated at the 11-position and the 21-position are described herein. Compounds having both an ethynyl substituent and a hydroxy substituent at the 18-position are also described herein. The compounds are useful as aldosterone inhibitors. Excerpt(s): Aldosterone is a steroidal hormone which is synthesized in the zona glomerulosa cells of the adrenal glands. The primary biological function of this compound is the regulation of salt retention and, in particular, aldosterone plays a major role in controlling the reabsorption of sodium ions from the urine by the kidney. Thus, a deficiency of the enzyme responsible for the synthesis of aldosterone is a characteristic of patients with a salt-losing syndrome, while primary hyperaldosteronism can result from hyperbiosynthesis of aldosterone as caused by an adrenocortical tumor or the administration of certain drugs. The hyperaldosteronism may involve hypertension, hypokalemia, alkalosis, muscular weakness, polyuria and polydipsia. Thus, treatment of hyperaldosteronism and the conditions associated with it would be possible by blockage of the enzymatic synthesis of aldosterone. The present invention relates to aldosterone inhibitors which are progesterone derivatives having a vinylidene or a 1-alkynyl substituent at the 18-position or both an ethynyl and a hydroxy substituent at the 18-position and optionally having a hydroxy substituent at the 11-position and the 21-position. The compounds of the present invention can be prepared from an appropriate pregnan-18-al. The 3- and 20-carbonyl groups ordinarily present in the starting materials used are usually protected as the ketal, preferably that obtained using ethylene glycol. More specifically, the protected compounds involved can be obtained by treatment of the appropriate pregnan-3,20-dione with ethylene glycol in the presence of a trace of acid. Alternatively, it may be possible to protect the 3position by reduction of the 3-ketone to the alcohol with lithium aluminum hydride followed by reaction with t-butyl dimethylsilyl chloride to give the corresponding ether. Any hydroxy groups present can be protected as the corresponding acetyl ester although it should be noted that any compound containing an 11-hydroxy group can exist in the form of an acetal with the 18-oxo group. Web site: http://www.delphion.com/details?pn=US04293548__
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Aldosterone antagonist and cyclooxygenase-2 inhibitor combination therapy to prevent or treat inflammation-related cardiovascular disorders Inventor(s): Blasi; Eileen R. (St. Louis, MO), McMahon; Ellen (Sunset Hills, MO), Rocha; Ricardo (Gurnee, IL), Zack; Marc (Evanston, IL) Assignee(s): Pharmacia Corporation (Chicago, IL) Patent Number: 6,716,829 Date filed: July 26, 2001 Abstract: Combinations of aldosterone blockers and Cyclooxygenase-2 inhibitors useful in the treatment of inflammation are disclosed. Excerpt(s): This invention is in the field of preventing or treating cardiovascular disorders. More specifically, this invention relates to the use of aldosterone antagonist and cyclooxygenase-2 inhibitor combination therapy in preventing or treating cardiovascular disease including atherosclerosis. Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of antiinflammatory drug discovery. However, common non-steroidal anti-inflammatory drugs (NSAID's) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAID's can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAID's is the use of corticosteroids, which also produce severe adverse effects, especially when long term therapy is involved. Recently, the role of inflammation in cardiovascular diseases is becoming more understood. Ridker et al. (New Eng. J. Med., 336, 973-9 (1997)) describes a possible role of inflammation in cardiovascular disease. J. Boyle (J. Path., 181, 93-9 (1997)) describes the association of plaque rupture and atherosclerotic inflammation. Web site: http://www.delphion.com/details?pn=US06716829__
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Aldosterone biosynthesis inhibitor Inventor(s): Fishman; Jack (Miami, FL), Hahn; Elliot (North Miami Beach, FL), Smith; Gregory A. (North Miami, FL) Assignee(s): Baker Cummins Pharmaceuticals, Inc. (Miami, FL) Patent Number: 5,120,724 Date filed: October 15, 1991 Abstract: Aldosterone biosynthesis inhibitors having substantially no intrinsic antiandrogenic activity are disclosed as well as pharmaceutical compositions containing such compounds and methods of treatment utilizing these compositions. Excerpt(s): The invention relates to inhibitors of aldosterone biosynthesis and compositions and methods for treating hyperaldosteronism. Primary aldosteronism is the constellation of chemical and clinical abnormalities resulting from the autonomous hypersecretion of the mineralocorticoid aldosterone, as opposed to secondary aldosteronism which refers to hypersecretion of aldosterone in response to a known stimulus such as angiotensin. Primary aldosteronism is most frequently caused by an
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aldosterone-secreting adenoma (Conn's syndrome), but it is sometimes associated with adrenal hyperplasia or can be idiopathic in origin. Web site: http://www.delphion.com/details?pn=US05120724__ •
Aldosterone-antagonistic steroids Inventor(s): Haga; Nobuhiro (Osaka, JP), Kamata; Susumu (Hyogo, JP), Matsui; Takeaki (Osaka, JP) Assignee(s): Shionogi & Co., Ltd. (Osaka, JP) Patent Number: 4,502,989 Date filed: January 5, 1984 Abstract: Novel spironolactone derivatives characterized by the C.sub.11 -C.sub.12 double bond which have a potent aldosterone-antagonistic activity without causing potassium loss, used alone in diagnosis and improvement of condition of primary aldosteronism, or together with other drugs in treatment of essential or renal hypertension as well as cardiac or renal edema; prepared from 3,17-bis(ethylene-dioxy)5,11-androstadiene. Excerpt(s): The present invention relates to steroid derivatives having aldosteroneantagonistic activity more potent than that of spironolactone. The aldosterone antagonists have widely been used alone in diagnosis and improvement of condition of primary aldosteronism, or together with other drugs in treatment of essential or renal hypertension as well as cardiac or renal edema since they antagionize aldosterone in the distalis urinary tubule to inhibit resorption of sodium and excretion of potassium and exhibit diuretic effect without causing potassium loss. The steroid derivatives of the present invention are novel compounds and characterized by the double bond at the C.sub.11 -C.sub.12 position of the steroid nucleous structure; they have a potent aldosterone-antagonistic activity and are useful compounds of which the pharmacological efficacy is expected to be applied in a medical field. Web site: http://www.delphion.com/details?pn=US04502989__
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Direct genetic test for glucocorticoid-remediable aldosteronism Inventor(s): Lalouel; Jean-Marc (Salt Lake City, UT), Lifton; Richard P. (Salt Lake City, UT) Assignee(s): Brigham and Women's Hospital (Boston, MA), University of Utah (Salt Lake City, UT) Patent Number: 5,529,900 Date filed: January 8, 1993 Abstract: A method of screening for glucocorticoid remediable aldosteronism (GRA) in a mammal by detecting the presence or absence of a chimaeric gene duplication resulting from unequal crossing over of the 11,.beta.-hydroxylase and aldosterone synthase genes, or the product encoded by the chimaeric gene duplication. Presence of the chimaeric gene duplication or its encoded product is indicative of a mammal afflicted with GRA and absence of the chimaeric gene duplication or its product is indicative of a mammal not afflicted with GRA.
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Excerpt(s): Hypertension, a widespread disorder of unknown cause, is responsible for over 200,000 deaths in the United States alone each year due to heart attack, stroke, and end stage renal disease. Population-based epidemiologic studies, adoption studies and twin studies have demonstrated a strong genetic component to hypertension. Glucocorticoid-remediable aldosteronism (GRA) is a disorder responsible for a form of hypertension. This disease is characterized by variably elevated levels of aldosterone, an adrenal gland steroid which regulates sodium-potassium metabolism, and high levels of the abnormal adrenal steroids, 18-hydroxycortisol and 18-oxocortisol. Currently the two ways to diagnose GRA require either measurement of aldosterone levels before and after administration of a glucocorticoid drug (e.g. dexamethasone), or measurement of 18-oxocortisol, 18-hydroxycortisol and the ratio of 18-oxocortisol to tetrahydroaldosterone in a 24 hour urine collection. Both of these tests are cumbersome and expensive and the latter test is available in the United States in only a few laboratories. Web site: http://www.delphion.com/details?pn=US05529900__ •
Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy Inventor(s): Alexander; John C. (Winnetka, IL), Gorczynski; Richard J. (Boulder, CO), Schuh; Joseph R. (St. Louis, MO) Assignee(s): G.D. Searle & Co. (Chesterfield, MO) Patent Number: 6,653,306 Date filed: January 9, 1997 Abstract: A combination comprising therapeutically-effective amount of an epoxysteroidal aldosterone receptor antagonist and a therapeutically-effective amount of an angiotensin II receptor antagonist is described for treatment of circulatory disorders. Excerpt(s): Combinations of an epoxy-steroidal aldosterone receptor antagonist and an angiotensin II receptor antagonist are described for use in treatment of circulatory disorders, including cardiovascular diseases such as hypertension, congestive heart failure, cardiac hypertrophy, cirrhosis and ascites. Of particular interest are therapies using an epoxy-containing steroidal aldosterone receptor antagonist compound such as epoxymexrenone in combination with an angiotensin II receptor antagonist compound. Myocardial (or cardiac) failure, whether a consequence of a previous myocardial infarction, heart disease associated with hypertension, or primary cardiomyopathy, is a major health problem of worldwide proportions. The incidence of symptomatic heart failure has risen steadily over the past several decades. In clinical terms, decompensated cardiac failure consists of a constellation of signs and symptoms that arises from congested organs and hypoperfused tissues to form the congestive heart failure (CHF) syndrome. Congestion is caused largely by increased venous pressure and by inadequate sodium (Na.sup.+) excretion, relative to dietary Na.sup.+ intake, and is importantly related to circulating levels of aldosterone (ALDO). An abnormal retention of Na.sup.+ occurs via tubular epithelial cells throughout the nephron, including the later portion of the distal tubule and cortical collecting ducts, where ALDO receptor sites are present. Web site: http://www.delphion.com/details?pn=US06653306__
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Immediate release eplerenone compositions Inventor(s): Gokhale; Rajeev D. (Waukegan, IL), Thosar; Shilpa S. (Des Plaines, IL), Tolbert; Dwain S. (Wadsworth, IL) Assignee(s): G. D. Searle & Co. (Skokie, IL) Patent Number: 6,410,054 Date filed: December 8, 1999 Abstract: The invention relates to oral pharmaceutical compositions useful as aldosterone receptor blockers comprising the active agent micronized eplerenone in an amount of about 10 mg to about 1000 mg and one or more carrier materials. Excerpt(s): The present invention relates to pharmaceutical compositions comprising the compound eplerenone as an active ingredient, and more particularly to pharmaceutical compositions containing micronized eplerenone, methods of treatment comprising administering such pharmaceutical compositions to a subject in need thereof, and the use of such compositions in the manufacture of medicaments. The compound methyl hydrogen 9,11.alpha.-epoxy-17.alpha.-hydroxy-3-oxopregn-4-ene-7.alpha.,21-dicarboxy late,.gamma.-lactone (also referred to herein as eplerenone) was first reported in Grob et al., U.S. Pat. No. 4,559,332 that describes and claims a class of 9,11-epoxy steroid compounds and their salts together with processes for the preparation of such compounds. These 9,11-epoxy steroid compounds are described as aldosterone antagonists that can be administered in a therapeutically effective amount to treat pathological conditions associated with hyperaldosteronism such as hypertension, cardiac insufficiency and cirrhosis of the liver. U.S. Pat. No. 4,559,332 contains general references to formulations for the administration of these 9,11-epoxy steroid compounds such as tablets and capsules. Ng et al., WO 98/25948 later disclosed additional synthetic processes for the preparation of a similar class of 9,11-epoxy steroid compounds and their salts, including eplerenone. Both U.S. Pat. No. 4,559,332 and WO 98/25948 are incorporated by reference herein. Web site: http://www.delphion.com/details?pn=US06410054__
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Method for inhibiting myocardial fibrosis by administering an aldosterone antagonist which suppresses aldoster one receptors Inventor(s): Weber; Karl T. (Columbia, MO) Assignee(s): Curators of the University of Missouri (Columbia, MO) Patent Number: 5,529,992 Date filed: December 2, 1993 Abstract: This invention discloses a method of using an aldosterone antagonist such as spironolactone, at a dosage which does not disrupt a patient's normal electrolyte and water-retention balance, to inhibit myocardial fibrosis, including left ventricular hypertrophy (LVH). Excerpt(s): This invention relates to drugs such as spironolactone which block the activity of the hormone aldosterone, and to the use of aldosterone-blocking drugs to prevent or treat myocardial fibrosis, a disease condition. In a medical context, fibrosis refers the creation of fibrotic tissue (i.e., tissue characterized by an abnormally high quantity of fibrous material, primarily strands of collagen). In some situations, fibrosis is useful and necessary, such as in the healing of wounds, but in other situations, fibrosis
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can be harmful, especially when it interferes with the functioning of internal organs. As one example, liver cirrhosis is usually characterized by high levels of fibrosis. That condition, discussed in the above-cited parent application, Ser. No. 07/871,390, is not directly relevant to this invention. This invention relates to the use of mineralocorticoid antagonists (such as spironolactone) in inhibiting myocardial fibrosis. Web site: http://www.delphion.com/details?pn=US05529992__ •
Spironolactone composition Inventor(s): Olsen; James L. (Chapel Hill, NC) Assignee(s): Carolina Medical Products, Inc. (Chapel Hill, NC) Patent Number: 4,837,211 Date filed: April 6, 1987 Abstract: A pharmaceutical composition, having utility as a diuretic or aldosterone antagonist, comprising spironolactone and an aqueous homogenizingly effective amount of a material selected from the group consisting of (i) sodium carboxymethylcellulose, and (ii) a mixture of methylcellulose and a dimethylpolysiloxane polymer.Also disclosed is a method of diuretic or hyperaldosteronism treatment by administration of such composition, e.g., by oral administration. Excerpt(s): This invention relates generally to pharmaceutical compositions having utility as diuretics and aldosterone antagonists, and specifically relates to spironolactone compositions of such type which are aqueously homogenizable in character. Spironolactone is a steroidal lactone compound having a significant aldosterone antagonistic character, which has been widely employed as a diuretic. The structure and preparation of this compound are disclosed in U.S. Pat. No. 3,257,390 to A. A. Patchett. Web site: http://www.delphion.com/details?pn=US04837211__
Patent Applications on Aldosterone 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 aldosterone: •
Aldosterone antagonist composition for release during aldosterone acrophase Inventor(s): Garthwaite, Susan M.; (Evanston, IL), Mathur, Leo K.; (Vernon Hills, IL) Correspondence: Steven J. Sarussi; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20020132001 Date filed: May 11, 2001
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This has been a common practice outside the United States prior to December 2000.
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Abstract: A pharmaceutical composition is provided for administration to a subject mammal such as a human exhibiting a diurnal cycle of plasma aldosterone concentration, the composition comprising a delayed-release formulation of an aldosterone antagonist drug, e.g., eplerenone, in a therapeutically effective amount. The delayed-release formulation, when administered about 6 hours to about 12 hours prior to the acrophase, results in a profile of plasma drug concentration that corresponds substantially to the diurnal cycle of plasma aldosterone concentration. Excerpt(s): This application claims priority of U.S. provisional application Serial No. 60/203,637 filed on May 12, 2000. The present invention relates to a pharmaceutical composition for treatment of circulatory disorders, including cardiovascular diseases such as hypertension, congestive heart failure and cardiomyopathy, and cardiovascular injury associated therewith. The invention relates more particularly to a pharmaceutical composition comprising as an active ingredient an aldosterone receptor antagonist, to a method of treatment comprising administering such a composition to a mammalian subject in need thereof, and to the use of such a composition in the manufacture of a medicament. Aldosterone antagonists are known to be useful in treatment of hypertension and associated cardiac disease or insufficiency. The steroid drug spironolactone is an aldosterone antagonist that has been available, for example under the trademark Aldactone.RTM., for many years for treatment of hypertension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Aldosterone blocker therapy to prevent or treat inflammation-related disorders Inventor(s): Rocha, Ricardo; (Flemington, NJ), Zack, Marc D.; (Winnetka, IL) Correspondence: Pharmacia Corporation; Global Patent Department; Post Office Box 1027; ST. Louis; MO; 63006; US Patent Application Number: 20040037806 Date filed: January 24, 2003 Abstract: A method of preventing or treating an inflammation-related disorder such as myocarditis, cardiomyopathy, vasculitis, and Behcet's disease in a subject, comprising treating the subject with a therapeutically-effective amount of an aldosterone blocker sufficient to alter the expression of one or more expression products involved, directly or indirectly, in the regulation of inflammation or cardiac remodeling in the subject. Excerpt(s): This invention is in the field of preventing or treating inflammation-related disorders, and more particularly inflammation-related cardiovascular disorders. More specifically, this invention relates to the use of aldosterone blocker therapy in preventing or treating cardiovascular disease including atherosclerosis. Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of anti-inflammatory drug discovery. However, common non-steroidal anti-inflammatory drugs (NSAID's) that are active in reducing the prostaglandininduced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAID's can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAID's is the use of corticosteroids, which also produce severe adverse effects, especially when long term therapy is involved. NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human
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arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated with inflammation (named "cyclooxygenase-2 (COX-2)" or "prostaglandin G/H synthase II") provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination of an aldosterone receptor antagonist and an HMG CoA reductase inhibitor Inventor(s): Keller, Bradley T.; (Chesterfield, MO), McMahon, Ellen G.; (Sunset Hills, MO), Rocha, Ricardo; (Gurnee, IL) Correspondence: Pharmacia Corporation; Global Patent Department; Post Office Box 1027; ST. Louis; MO; 63006; US Patent Application Number: 20030149010 Date filed: July 18, 2002 Abstract: Novel methods and combinations for the treatment and/or prophylaxis of a pathologic condition in a subject, wherein the methods comprise the administration of one or more HMG Co-A reductase inhibitors and one or more aldosterone receptor antagonists, and the combinations comprise one or more HMG Co-A reductase inhibitors and one or more of said aldosterone receptor antagonists. Excerpt(s): The present invention relates to methods for the treatment and/or prophylaxis of one or more pathogenic effects in a subject arising from or exacerbated by endogenous mineralocorticoid activity, especially in the presence of dyslipidemia or in a subject susceptible to or suffering from dyslipidemia. Particularly, the invention relates to the use of an aldosterone receptor antagonist combined with the use of an HMG CoA reductase inhibitor for the treatment of one or more pathogenic effects selected from, but not limited to, cardiovascular-related conditions, inflammationrelated conditions, neurological-related conditions, musculo-skeletal-related conditions, metabolism-related conditions, endocrine-related conditions, dermatologic-related conditions and cancer-related conditions. More particularly, the invention relates to treating one or more of said conditions with said combination therapy, wherein the aldosterone receptor antagonist is an epoxy-steroidal compound, such as eplerenone. Aldosterone (ALDO) is the body's most potent known mineralocorticoid hormone. As connoted by the term mineralocorticoid, this steroid hormone has mineral-regulating activity. It promotes Na.sup.+ reabsorption not only in the kidney, but also from the lower gastrointestinal tract and salivary and sweat glands, each of which represents classic ALDO-responsive tissues. ALDO regulates Na.sup.+ and water resorption at the expense of potassium (K.sup.+) and magnesium (Mg.sup.2+) excretion. ALDO can also provoke responses in nonepithelial cells. These responses can have adverse consequences on the structure and function of the cardiovascular system and other tissues and organs. Hence, ALDO can contribute to the organ failures for multiple reasons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combination of organic compounds Inventor(s): Steele, Ronald Edward; (Long Valley, NJ) Correspondence: Thomas Hoxie; Novartis, Patent And Trademark Department; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030083342 Date filed: August 27, 2002 Abstract: The invention relates to a pharmaceutical composition, of (i) an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereofeither alone or in combination with (ii) an AT.sub.1-receptor antagonist combined with a diuretic, or in each case, a pharmaceutically acceptable salt thereof and (iii) a pharmaceutically acceptable carrier. Excerpt(s): (c) endothelial dysfunction with or without hypertension, comprising administering the pharmaceutical composition of the present invention. In a preferred embodiment the present invention relates to a method of prevention of, delay of progression of or treatment of endothelial dysfunction with or without hypertension comprising administering to a warm-blooded animal, including man, in need thereof an effective amount of an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof. AT.sub.1-receptor antagonists (also called angiotensin II receptor antagonists) are understood to be those active ingredients which bind to the AT.sub.1receptor subtype of angiotensin 11 receptor but do not result in activation of the receptor. As a consequence of the inhibition of the AT.sub.1 receptor, these antagonists can, for example, be employed as antihypertensives or for treating congestive heart failure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Controlled release eplerenone compositions Inventor(s): Gokhale, Rajeev D.; (Waukegan, IL), Thosar, Shilpa S.; (Des Plaines, IL), Tolbert, Dwain S.; (Wadsworth, IL) Correspondence: Pharmacia Corporation; Corporate Patent Department; 800 N. Lindbergh Boulevard - 04b; ST. Louis; MO; 63167; US Patent Application Number: 20020136775 Date filed: January 31, 2002 Abstract: The invention relates to oral pharmaceutical compositions useful as aldosterone receptor blockers comprising the active agent micronized eplerenone in an amount of about 10 mg to about 1000 mg and one or more carrier materials. Excerpt(s): The present invention relates to pharmaceutical compositions comprising the compound eplerenone as an active ingredient, and more particularly to pharmaceutical compositions containing micronized eplerenone, methods of treatment comprising administering such pharmaceutical compositions to a subject in need thereof, and the use of such compositions in the manufacture of medicaments. The compound methyl hydrogen 9,11.alpha.-epoxy-17.alpha.-hydroxy-3-oxopregn-4-ene-7.alpha.,21dicarboxylate,.gamma.-lactone (also referred to herein as eplerenone) was first reported in Grob et al., U.S. Pat. No. 4,559,332 that describes and claims a class of 9,11-epoxy steroid compounds and their salts together with processes for the preparation of such compounds. These 9,11-epoxy steroid compounds are described as aldosterone
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antagonists that can be administered in a therapeutically effective amount to treat pathological conditions associated with hyperaldosteronism such as hypertension, cardiac insufficiency and cirrhosis of the liver. U.S. Pat. No. 4,559,332 contains general references to formulations for the administration of these 9,11-epoxy steroid compounds such as tablets and capsules. Ng et al., WO 98/25948 later disclosed additional synthetic processes for the preparation of a similar class of 9,11-epoxy steroid compounds and their salts, including eplerenone. Both U.S. Pat. No. 4,559,332 and WO 98/25948 are incorporated by reference herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hormone replacement therapy with cardiovascular protection using antialdosteronic progestins Inventor(s): Mayerhofer, Siegfried; (Vienna, AT) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040087563 Date filed: November 5, 2002 Abstract: The present invention relates to methods of treating aldosterone-mediated diseases such as cardiovascular diseases in peri-menopausal or post-menopausal women by administering an agent with antimineralocorticoid and progestational activity, in particular drospirenone. Excerpt(s): The present invention relates to a pharmaceutical composition comprising drospirenone as the sole therapeutically active agent and to methods of treating symptoms and diseases related to deficient levels of progesterone, in particularly to methods of simulataneous treating symptoms and diseases related to deficient levels of progesterone and aldosterone-mediated diseases such as cardiovascular diseases. A number of mechanisms are now recognised in the pathogenesis of cardiovasculary diseases. For long it has been the understanding that the predominant mechanism of preventing hypertension was through maintaining electrolyte homeostasis via the reninangiotensin-aldosterone system (RAAS) in that the plasma levels of the mineralocorticoid hormone, aldosterone, was reduced by inhibiting the angiotensin converting enzyme. Aldosterone has been known to exert its activities through activation of mineralocorticoid receptors present in the epithelia of the kidney, colon and sweat glands whereby aldosterone promote the retention of sodium and the excretion of potassium. One of the most widely used agents for reducing hypertension is the so-called ACE inhibitors that act through inhibition of the angiotensin-converting enzyme. Hypertension has for many years been thought to be the pre-dominant factor in the development of cardiovascular diseases, but it has now been questioned to what extent ACE inhibitors prevents the development of cardiovascular diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method to treat cardiofibrosis with a combination therapy of an angiotensin II antagonist and an epoxy-steroidal aldosterone antagonist Inventor(s): Egan, James J.; (Winnetka, IL), McMahon, Ellen G.; (St. Louis, MO), Olins, Gillian M.; (Glencoe, MO), Schuh, Joseph R.; (St. Louis, MO) Correspondence: Pharmacia Corporation; Global Patent Department; Post Office Box 1027; ST. Louis; MO; 63006; US Patent Application Number: 20040053903 Date filed: February 21, 2003 Abstract: A therapeutic method is described for treating cardiofibrosis or cardiac hypertrophy using a combination therapy comprising a therapeutically-effective amount of an epoxy-steroidal aldosterone receptor antagonist and a therapeuticallyeffective amount of an angiotensin II receptor antagonist. Preferred angiotensin II receptor antagonists are those compounds having high potency and bioavailability and which are characterized in having an imidazole or triazole moiety attached to a biphenylmethyl or pyridinyl/phenylmethyl moiety. Preferred epoxy-steroidal aldosterone receptor antagonists are 20-spiroxane steroidal compounds characterized by the presence of a 9.alpha., 11.alpha.-substituted epoxy moiety. A preferred combination therapy includes the angiotensin II receptor antagonist 5-[2-[5-[(3,5dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-pyridinyl]phenyl-1H-tetrazole and the aldosterone receptor antagonist epoxymexrenone. Excerpt(s): Therapeutic methods are described for treatment of cardiofibrosis and cardiac hypertrophy. Of particular interest are therapies using an epoxy-containing steroidal aldosterone receptor antagonist compound such as epoxymexrenone in combination with an angiotensin II receptor antagonist compound. Myocardial (or cardiac) failure, whether a consequence of a previous myocardial infarction, heart disease associated with hypertension, or primary cardiomyopathy, is a major health problem of worldwide proportions. The incidence of symptomatic heart failure has risen steadily over the past several decades. In clinical terms, decompensated cardiac failure consists of a constellation of signs and symptoms that arises from congested organs and hypoperfused tissues to form the congestive heart failure (CHF) syndrome. Congestion is caused largely by increased venous pressure and by inadequate sodium (Na.sup.+) excretion, relative to dietary Na.sup.+ intake, and is importantly related to circulating levels of aldosterone (ALDO). An abnormal retention of Na.sup.+ occurs via tubular epithelial cells throughout the nephron, including the later portion of the distal tubule and cortical collecting ducts, where ALDO receptor sites are present. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for the treatment or prophylaxis of aldosterone-mediated pathogenic effects in a subject using an epoxy-steroidal aldosterone antagonist Inventor(s): Fedde, Kenton N.; (Webster Groves, MO), Funder, John W.; (Victoria, AU), Garthwaite, Susan M.; (Evanston, IL), Rocha, Ricardo; (Gurnee, IL), Roniker, Barbara; (Chicago, IL), Williams, Gordon H.; (Belmont, MA) Correspondence: Pharmacia Corporation; Corporate Patent Department; 800 North Lindbergh BLVD.; Mail Zone O4e; ST. Louis; MO; 63167; US Patent Application Number: 20030096798 Date filed: December 13, 2001
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Abstract: The present invention provides methods for the treatment or prophylaxis of one or more aldosterone-mediated pathogenic effects in a subject suffering from or susceptible to the pathogenic effect or effects wherein the subject has one or more conditions selected from the group consisting of a sub-normal endogenous aldosterone level, salt sensitivity and an elevated dietary sodium intake. The methods comprise administering to the subject a therapeutically-effective amount of one or more epoxysteroidal compounds that are aldosterone antagonists. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/709,253 filed Nov. 8, 2000, which claims priority from U.S. Provisional Patent Application Serial No. 60/164,390 filed Nov. 9, 1999. This application also is a continuation-in-part of U.S. patent application Ser. No. 09/713,348 filed Nov. 14, 2000, and claims priority from U.S. Provisional Patent Application Serial No. 60/211,064 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,250 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,253 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,264 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,311 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,340 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,451 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/211,459 filed Jun. 13, 2000; and U.S. Provisional Patent Application Serial No. 60/221,358, filed Jul. 27, 2000; and U.S. Provisional Patent Application Serial No. 60/221,364 filed Jul. 27, 2000; and U.S. Provisional Patent Application Serial No. 60/233,056 filed Sep. 14, 2000. The present invention relates to methods for the treatment and/or prophylaxis of one or more pathogenic effects in a subject resulting from the action of endogenous aldosterone, especially in the presence of an elevated sodium level. More particularly, the invention relates to the use of epoxy-steroidal compounds that are aldosterone antagonists, such as eplerenone, for the treatment and/or prophylaxis of hypertension, cardiovascular disease and/or renal dysfunction in a human subject having a sub-normal aldosterone level, salt sensitivity and/or an elevated dietary sodium intake. Essential hypertension is a major vascular disease throughout the world and represents a significant public health problem. Elevated blood pressure associated with hypertension has been linked to the incidence of coronary heart disease and stroke. For example, Blumenfeld J D and Laragh J H. Congestive heart failure: pathophysiology, diagnosis and management, 1.sup.st ed. Caddo (OK): Professional Communications, Inc.; 1994, reported that hypertension triples the risk for developing heart failure. Similarly, MacMahon S et al.: Lancet 1990;335:765-71, reported that a prolonged reduction of only 5 mm Hg in diastolic blood pressure results in a reduction of at least 20 percent of the risk for developing coronary heart disease and at least 33 percent of the risk for developing stroke. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treating ophthalmic disorders with epoxy-steroidal aldosterone receptor antagonists Inventor(s): Aiken, James W.; (Basking Ridge, NJ) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20030158162 Date filed: December 12, 2002
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Abstract: A method for treating or preventing ophthalmic disorders comprising the administration of one or more aldosterone receptor antagonists that contain a 9,11epoxy moiety, such as eplerenone is disclosed. The method results in a reduction of intraocular pressure which treats or prevents the ophthalmic disorders. Among the disorders are intraocular hypertension, glaucoma, low tension glaucoma, age-related macular degeneration (AMD), macular edema, and diabetic retinopathy.As glucocorticoids and mineralocorticoids also cause the retention of ions, such as sodium and potassium, where aldosterone receptors are located, aldosterone receptor antagonists that contain a 9,11-epoxy moiety, such as eplerenone, also can be administered to modulate the intraocular concentration of ions. Thus, aldosterone receptor antagonists can be administered to maintain an intraocular ionic environment that is beneficial to intraocular cell survival. Excerpt(s): This application is a complete application based on U.S. provisional application Serial No. 60/341,033, filed Dec. 12, 2001 and the entire disclosure of which is incorporated herein by reference. The present invention relates to novel methods for the treatment or prevention of glaucoma, ocular hypertension, and other ophthalmic disorders exhibiting elevated intraocular pressure, as well as ocular disorders characterized by retinal neurodegeneration or edema including glaucoma, diabetic retinopathy, and adult macular degeneration with one or more epoxy-steroidal aldosterone receptor antagonists. Glaucoma is a group of diseases that can lead to damage to the eye's optic nerve and result in blindness. The optic nerve connects the retina, the light-sensitive layer of nerve cells at the back of the eye, with the brain. A healthy optic nerve is necessary for good vision. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Modulation of matrix metalloproteinase (MMP) activity with aldosterone blocker(s) Inventor(s): McMahon, Ellen G.; (St. Louis, MO), Rudolph, Amy E.; (St. Louis, MO) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040048840 Date filed: August 22, 2003 Abstract: The present invention is directed to a method for preventing an increase in matrix metalloproteinase (MMP) activity or reducing MMP activity in a subject in need thereof by administering to the subject a therapeutically effective amount of a selective aldosterone blocker. More particularly, the present invention is directed to attenuating or preventing an increase in MMP activity comprising administering eplerenone, or derivatives thereof. Excerpt(s): This application is a non-provisional of provisional application Serial No. 60/405,292 filed Aug. 23, 2003, the contents of which is incorporated herein in its entirety. The present invention is directed to a method for preventing an increase in matrix metalloproteinase (MMP) activity or reducing MMP activity in a subject. More particularly, the present invention is directed to attenuating MMP activity or preventing an increase in MMP activity comprising administering eplerenone, or derivatives thereof, in a therapeutically effective amount to a subject in need thereof. MMPs are a family of zinc-dependent endopeptidases that have the capacity to degrade the extracellular matrix (ECM). The controlled/coordinated breakdown of ECM permits normal operation of metabolic processes, proper operation of homeostatic degradation
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and repair of ECM to maintain structural and spatial tissue integrity and tissue morphology necessary to maintain normal life-sustaining functions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of aldosterone antagonists to inhibit myocardial fibrosis Inventor(s): Weber, Karl T.; (Columbia, MO) Correspondence: Susan J Wharton; Shook Hardy & Bacon Llp; 1200 Main Street; Kansas City; MO; 64105-2118; US Patent Application Number: 20020013303 Date filed: April 24, 2000 Abstract: This invention discloses a method of using an aldosterone antagonist such as spironolactone, at a dosage which does not disrupt a patient's normal electrolyte and water-retention balance, to inhibit myocardial fibrosis, including left ventricular hypertrophy (LVH). Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 07/871,390, filed on Apr. 21, 1992. This invention relates to drugs such as spironolactone which block the activity of the hormone aldosterone, and to the use of aldosteroneblocking drugs to prevent or treat myocardial fibrosis, a disease condition. In a medical context, fibrosis refers the creation of fibrotic tissue (i.e., tissue characterized by an abnormally high quantity of fibrous material, primarily strands of collagen). In some situations, fibrosis is useful and necessary, such as in the healing of wounds, but in other situations, fibrosis can be harmful, especially when it interferes with the functioning of internal organs. As one example, liver cirrhosis is usually characterized by high levels of fibrosis. That condition, discussed in the above-cited parent application, Ser. No. 07/871,390, is not directly relevant to this invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of an aldosterone receptor antagonist to improve cognitive function Inventor(s): Fedde, Kenton N.; (Webster Groves, MO), Perez, Alfonzo T.; (Lake Forest, IL), Tooley, Joseph F.; (Park Ridge, IL) Correspondence: Scott A. Williams; Pharmacia Corporation; Corporate Patent Department; 800 N. Lindbergh BLVD., Mail Zone O4e; ST. Louis; MO; 63167; US Patent Application Number: 20020111337 Date filed: August 28, 2001 Abstract: Aldosterone receptor antagonists for the prevention and treatment of cognitive dysfunction are disclosed. Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/228,738 filed Aug. 28, 2000. Cognitive and mood dysfunctions are a group of disorders characterized by either confusion, disorientation, memory disturbances, behavioral disorganization, depression, and disordered autonomic functioning (e.g. altered activity rhythms, sleep, and appetite). In many cases, definable neuropathological or metabolic disturbances underlie these conditions; in other cases, the etiological basis remains unknown. Of historic significance, treatment of
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cardiovascular disease with antihypertensive agents such as reserpine often caused depression, leading researchers to hypotheses of the role of the adrenergic system in mental illness. Previous studies have indicated a relationship between aldosterone levels and mood (Birmingham M K, Barta A, Solyom L, Lehoux J G, Vecsei P. Correlations between mood scores, LH, adrenocortical steroids, and urine volumes in a patients with a history of postpartum depression and monthly psychotic episodes. Endocrin Res 1998;24:595-599). 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 aldosterone, 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 “aldosterone” (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 aldosterone. You can also use this procedure to view pending patent applications concerning aldosterone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON ALDOSTERONE Overview This chapter provides bibliographic book references relating to aldosterone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on aldosterone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “aldosterone” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on aldosterone: •
Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment Source: Malden, MA: Blackwell Science, Inc. 1999. 568 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781)-388-8250. Fax (781) 388-8270. E-mail:
[email protected]. Website: www.blackwellscience.com. PRICE: $125.00 plus shipping and handling. ISBN: 0632043423. Summary: Cirrhosis (liver scarring) is a very prevalent disease and ascites (fluid accumulation) is the most frequent complication. The development of ascites in cirrhosis is the consequence of the simultaneous occurrence of very complex processes leading to impairment in hepatic, circulatory, and renal function. The textbook offers 32 chapters on the pathogenesis, diagnosis and treatment of ascites and renal dysfunction in liver disease. Topics include historical notes on ascites in cirrhosis; characteristics of ascites;
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clinical disorders of renal function in cirrhosis with ascites; clinical disorders of renal function in acute liver failure; renal dysfunction and postoperative renal failure in obstructive jaundice; spontaneous bacterial peritonitis; the etiology, diagnosis, and management of noncirrhotic ascites; extracellular fluid volume homeostasis; physiology of the renal circulation; physiology of the gastrointestinal and liver circulation; the renin angiotensin aldosterone system in cirrhosis; the sympathetic nervous system in cirrhosis; arginine vasopressin in cirrhosis; atrial natriuretic peptide and other natriuretic factors in cirrhosis; arachidonic acid metabolites and the kidney in cirrhosis; nitric oxide and systemic and renal hemodynamic disturbances in cirrhosis; endothelin and systemic, renal, and hepatic hemodynamic disturbances in cirrhosis; the systemic circulation in cirrhosis; the splanchnic circulation in cirrhosis; alterations of hepatic and splanchnic microvascular exchange in cirrhosis (local factors in the formation of ascites); experimental models in the investigation of portal hypertension; renal dysfunction and ascites in carbon tetrachloride induced cirrhosis in rates; bacterial infection of the ascitic fluid in rates with carbon tetrachloride induced cirrhosis; the arterial vasodilation hypothesis of ascites formation in cirrhosis; prognosis of cirrhosis with ascites; the medical treatment of ascites in cirrhosis; treatment of ascites by paracentesis; the treatment of refractory ascites in cirrhosis; the treatment of hepatorenal syndrome in cirrhosis; drug induced renal failure in cirrhosis; liver transplantation in cirrhotic patients with ascites; and the treatment and prophylaxis of spontaneous bacterial peritonitis. Each chapter is written by experts in the field and includes extensive references. The text concludes with a subject index. •
Renal Failure: Blackwell's Basics of Medicine Source: Oxford, England: Blackwell Science Ltd. 1995. 295 p. Contact: Available from Blackwell Science, Inc. 238 Main Street, Cambridge, MA 02142. (800) 215-1000 or (617) 876-7000. Fax (617) 492-5263. PRICE: $24.95. ISBN: 0865424306. Summary: This book for health professionals on renal failure is from a series that examines relevant topics in medicine using concepts that pertain to the basic sciences. In this series, readers learn to interpret clinical data based on pathophysiological concepts. Four sections in this book cover the following issues: essentials, pathophysiology, clinical picture, and management of renal failure. Each section offers questions, with answers of one or two paragraphs on relevant topics. The 555 questions are numbered for ease of access through the subject index. Specific topics covered include: the anatomy of the kidneys, the kidney function tests used for diagnosis and monitoring, electrolyte function, urine concentration and dilution, oral water load, the roles of aldosterone, the role of the kidney in acid base balance, potassium, dietary therapy, chronic renal failure, polyuria, water and salt homeostasis, metabolic acidosis, renal tubular acidosis, hyperkalemia, acute tubular necrosis, uremia, renal impairment associated with diabetes mellitus, etiology of renal failure, hepatorenal syndrome, obstructive uropathy, anemia and erythropoietin, osteodystrophy, dialysis, prognosis, cost factors, and kidney transplantation.
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
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NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “aldosterone” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “aldosterone” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “aldosterone” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Regulation of aldosterone biosynthesis by Jürg Müller; ISBN: 3540052135; http://www.amazon.com/exec/obidos/ASIN/3540052135/icongroupinterna
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Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects by Jurg Muller; ISBN: 0387179070; http://www.amazon.com/exec/obidos/ASIN/0387179070/icongroupinterna
Chapters on Aldosterone In order to find chapters that specifically relate to aldosterone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and aldosterone using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “aldosterone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on aldosterone: •
Primary Aldosteronism Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 19-25. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Primary aldosteronism is characterized by hypertension (high blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood), and alkalosis with increased urinary potassium excretion and decreased urinary sodium. Many patients with aldosteronism exhibit certain forms of diabetes. This chapter on primary aldosteronism is from an exhaustive textbook on urologic surgery. The electrolyte and acid base disorders of aldosteronism are readily understood as a consequence of excessive production of aldosterone. The diagnosis can be confirmed by measurement of plasma aldosterone levels, bearing in mind that there will be a diurnal variation and postural responses. A more reliable method is the measurement of 24 hour urinary excretion values of aldosterone levels. The author stresses that the etiology of primary adosteronism must be established before treatment plans are established. Patients with adrenal carcinoma most certainly should have adrenalectomy (removal of the adrenal glands), preferably by open surgery and usually through the transabdominal approach. Patients with idiopathic hyperplasia as a cause of aldosteronism are best managed medically because surgical removal of the adrenals rarely will result in control of hypertension. The author describes the recommended surgical technique for adrenalectomy, and reviews the expected outcomes and potential complications. The most significant complication of surgery of aldosteronism is the persistence of hypertension. 7 figures. 10 references.
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Atrial Natriuretic Factor and Its Clinical Implications Source: in Andreucci, V.E. International Yearbook of Nephrology 1990. Norwell, MA: Kluwer Academic Publishers. 1990. p. 17-33. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. Hingham, MA: Kluwer Academic Publishers. 1990. p. 17-33. Summary: This chapter discusses the nature of the atrial natriuretic factor (ANF), a peptide hormone derived from the atria of the heart (the distension of which provokes diuresis, natriuresis and suppression of renin, and is affected by fluid balance), and its clinical significance. Topics include: ANF actions, including renal effects (hemodynamic effects; effects on tubular transport; mechanism of the natriuresis) and effects on the renin-angiotensin-aldosterone system (inhibition of renin secretion and aldosterone production; antagonism of angiotensin II), vascular smooth muscle, fluid shifts between compartments, and vasopressin; transduction of the ANF signal; ANF secretion; and specific clinical implications of ANF. Overall, ANF occupies a strategic position in the network of systems which maintain intravascular volume homeostasis; however, the precise physiologic role of ANF remains to be delineated. Potential therapeutic uses of ANF in hypertension, acute renal failure, and heart failure are currently being defined. 130 references.
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Endocrine Disturbances Source: in Daugirdas, J.T. and Ing, T.S., eds. Handbook of Dialysis. 2nd ed. Boston, MA: Little, Brown and Company. 1994. p. 491-502. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail:
[email protected]. Website: http://www.lrpub.com. PRICE: $37.95. ISBN: 0316173835. Summary: This chapter on endocrine disturbances is from a handbook that outlines all aspects of dialysis therapy, emphasizing the management of dialysis patients. The authors note that the various endocrine systems of dialysis patients are derange in subtle, often complex, ways. Consequently, interpretation of standard tests of endocrine function and diagnosis of endocrine deficiency or excess can be difficult. Topics include insulin, glucagon, renin-angiotensin, aldosterone, norepinephrine and epinephrine, cortisol, thyroid function, testicular function, ovarian function, growth hormone, parathyroid hormone, and vitamin D3. The authors present information in outline form, for easy reference. 1 table. 29 references.
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Hypokalemia and Hyperkalemia Source: in Mandal, A.K. and Nahman, N.S., Jr., eds. Kidney Disease in Primary Care. Baltimore, MD: Williams and Wilkins. 1998. p. 81-93. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. E-mail:
[email protected]. PRICE: $39.95. ISBN: 0683300571. Summary: This chapter on hypokalemia (low potassium levels) and hyperkalemia (elevated potassium levels) is from a textbook that provides primary care physicians with practical approaches to common clinical problems of kidney diseases. For each condition, the author outlines the basics, associated conditions, causes, signs and
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symptoms, diagnostic considerations, management strategies, and indications for referral. Hypokalemia is more common in patients who use thiazide, rather than loop, diuretics. As a rule, oral potassium is the safest form of replacement. Potassium chloride is the preparation of choice. Magnesium depletion often will cause renal potassium wasting, preventing potassium replacement from being effective. Aldosterone and the flow rate in the distal tubule of the kidney work together to effect potassium homeostasis (balance). A normal plasma potassium (whole blood) in the presence of elevated serum potassium concentrations confirms the diagnosis of pseudohyperkalemia. A review of medications taken by patients with hyperkalemia is critical, particularly for patients with renal insufficiency. In all patients with hyperkalemia, the possibilities of adrenal insufficiency and selective hypoaldosteronism should be considered. The chapter concludes with the answers to questions commonly asked by patients with potassium problems. 4 figures. 6 tables. 3 references. •
Renal Physiology and the Pathology of Renal Failure Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 25-34. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail:
[email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: This chapter on renal physiology and the pathology of renal failure is from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. The author of the chapter reviews the two prime functions of the normal kidney: elimination of metabolic wastes and other toxic materials; and maintenance of a stable composition of the body's internal fluid environment. In addition, kidneys also have several endocrine functions including: production of renin, which affects sodium, fluid volume, and blood pressure; erythropoietin formation, which controls red cell production in the bone marrow; production of prostaglandins; and involvement in the kallikreinkinin system. Also, the normal kidney is a receptor site for several hormones: antidiuretic hormone (ADH), produced by the pituitary, which reduces the excretion of water; aldosterone, produced by the adrenal cortex, which promotes sodium retention and enhances secretion of potassium and hydrogen ion; and parathyroid hormone, which increases phosphorus and bicarbonate excretion and stimulates conversion of vitamin D to the active form. The author describes each of these functions in detail, and the related problems that occur during reduced kidney function or kidney failure. 3 figures. 1 table.
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Pathogenesis of Edema in the Nephrotic Syndrome Source: in Seldin, D.W.; Griebisch, G., eds. Regulation of Sodium and Chloride Balance. New York, NY: Raven Press. 1990. p. 321-351. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 869-3495. PRICE: $76.50 plus shipping (as of 1995). ISBN: 0881674818. Summary: This chapter, from a book about the regulation of sodium and chloride balance, discusses the pathogenesis of edema in the nephrotic syndrome. Topics include the history of this condition, circulatory insufficiency, hyproteinemia and the regulation of blood volume, renal function in the nephrotic syndrome, a comparison of patients
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with minimal lesions and patients with histologic lesions, and the treatment of nephrotic edema. The authors also consider the hypovolemia concept, blood volume measurements, blood pressure and cardiac output, renin and aldosterone, other neurohumoral factors, hypoproteinemia and the Starling forces, glomerular permselectivity, renal hemodynamics, excretion of sodium chloride and water, the effects of manipulations, and observations during initiation and recovery. 12 figures. 1 table. 40 references. •
Endocrine Disease Source: in Miller, R.L., et al. General and Oral Pathology for the Dental Hygienist. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 309-320. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $43.00 plus shipping and handling. ISBN: 0801670241. Stock Number 07024. Summary: This chapter, from a textbook on pathology for dental hygiene students, covers endocrine disease. Topics include the clinical aspects of hyper-and hypopituitarism; diabetes insipidus; the development of the thyroid gland, and the physiology and function of the thyroglossal duct cyst and the lingual thyroid gland; common causes of myxedema; the etiology of Hashimoto's disease; the etiology and clinical symptoms of Graves' disease; thyroid cancer and its relationship to radiation or genetic etiology; goiter; the etiology, pathogenesis, and clinical features of FriderichsenWaterhouse syndrome, Addison's disease, and Cushing's syndrome; diseases caused by hypersecretion of aldosterone and adrenal sex hormones; the clinical and radiographic changes indicative of hyperparathyroidism; diabetes mellitus (types I and II); and common dental problems associated with diabetes mellitus. The chapter includes a list of learning objectives; illustrative case studies; and recommended readings. 4 figures. 2 tables.
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Urine Tests: Examining the Body's Excess Fluids Source: in Shaw, M., et al., eds. Everything You Need to Know About Medical Tests. Springhouse, PA: Springhouse Corporation. 1996. p. 549-616. Contact: Available from Springhouse Publishing. Attention: Trade and Textbook Department, 1111 Bethlehem Pike, P.O. Box 908, Springhouse, PA 19477-0908. (800) 3313170 or (215) 646-4670 or (215) 646-4671. Fax (215) 646-8716. PRICE: $24.95 (as of 1995). ISBN: 0874348234. Summary: This lengthy chapter, from a consumer handbook about medical practice and disease, presents information on urine tests used for diagnosis. Written in a question and answer format, the chapter discusses urine tests for these functions, diseases, and substances: kidney stones, kidney function, phosphate reabsorption by the kidneys, amylase, arysulfatase A, lysozyme, aldosterone, Cushing's syndrome, epinephrine, norepinephrine, dopamine, estrogens, pregnancy, placental estriol, pregnanetriol, vanillylmandelic acid, homovanillic acid, hydroxyindoleacetic acid, pregnanediol, proteins, Bence Jones protein, amino acid disorders, creatinine, creatinine clearance by the kidneys, urea clearance by the kidneys, uric acid, hemoglobin, myoglobin, porphyrins, delta-aminolevulinic acid, bilirubin, urobilinogen, sugar, glucose, ketones, vitamin B6, vitamin C, sodium, chloride, potassium, calcium, phosphates, magnesium, and iron. For each test discussed, the authors provide information about why the test is
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done, how the test is performed, what to do before the test, and what the results indicate.
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM 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 “aldosterone” (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 27150 245 141 12 107 27655
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 “aldosterone” (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 aldosterone 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 aldosterone. 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 aldosterone. 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 “aldosterone”:
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Addison's Disease http://www.nlm.nih.gov/medlineplus/addisonsdisease.html Adrenal Gland Disorders http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.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 aldosterone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: 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 aldosterone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with aldosterone. 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 aldosterone. 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 “aldosterone” (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 “aldosterone”. 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 “aldosterone” (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 “aldosterone” (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/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on aldosterone: •
Basic Guidelines for Aldosterone Aldosterone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003704.htm
•
Signs & Symptoms for Aldosterone Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm
•
Diagnostics and Tests for Aldosterone Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm
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Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •
Background Topics for Aldosterone Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Adrenal glands Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002219.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Distal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002346.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Renal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002289.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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ALDOSTERONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 18-Hydroxycorticosterone: 11 beta,18,21-Trihydroxypregn-4-ene-3,20-dione. [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] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Actin: Essential component of the cell skeleton. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA
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and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the
Dictionary 189
complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] 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] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Aldosterone Antagonists: Compounds which inhibit or antagonize the biosynthesis or actions of aldosterone. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH]
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Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allograft: An organ or tissue transplant between two humans. [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] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and
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kidneys. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiotensin I: The decapeptide precursor of angiotensin II, generated by the action of renin on angiotensinogen. It has limited pharmacologic activity. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Angiotensins: Oligopeptides ranging in size from angiotensin precursors with 14 amino acids to the active vasoconstrictor angiotensin II with 8 amino acids, or their analogs or derivatives. The amino acid content varies with the species and changes in that content produce antagonistic or inactive compounds. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test
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new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] 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] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are
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split to give products that have unpaired electrons. This process is called oxidation. [NIH] 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Coarctation: Narrowing of the lumen of the aorta, caused by deformity of the aortic media. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apnoea: Cessation of breathing. [EU] 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] Aquaporins: Membrane proteins which facilitate the passage of water. They are members of the family of membrane channel proteins which includes the lens major intrinsic protein and bacterial glycerol transporters. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argipressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, cyclic 1-6 disulfide. The usual mammalian antidiuretic hormone, it is a cyclic nonapeptide with arginine in position 8 of the chain. Argipressin is used to treat diabetes insipidus and as hemostatic because of its vasoconstrictor action. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU]
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Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] 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] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascitic Fluid: The serous fluid which accumulates in the peritoneal cavity in ascites. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] 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] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH]
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Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]
Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH]
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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] Biotinylation: Incorporation of biotinyl groups into molecules. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone 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 scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] 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] Brachial: All the nerves from the arm are ripped from the spinal cord. [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] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH]
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Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] 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] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Canrenoate Potassium: A synthetic pregnadiene derivative with anti-aldosterone activity. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of
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arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbenoxolone: An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [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] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell
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membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] 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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that
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develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chiasma: An anatomy term for an X-shaped crossing (for example, of nerves or tendons.) [NIH]
Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH]
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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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] 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 leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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
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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] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that
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provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] 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] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a
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congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [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] Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. [NIH]
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Cyst: A sac or capsule filled with fluid. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decongestant: An agent that reduces congestion or swelling. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the
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dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desmopressin: A synthetic analog of the natural hormone 8-arginine vasopressin (argipressin). Its action is mediated by the vasopressin receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating factor VIII and von Willebrand factor. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops
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(mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] 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] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [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] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Diurnal: Occurring during the day. [EU] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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] 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] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids;
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includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] 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] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear
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particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] 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]
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Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] 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] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [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] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [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] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH]
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Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]
Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Membrane Oxygenation: Application of a life support system that circulates the blood through an oxygenating system, which may consist of a pump, a membrane oxygenator, and a heat exchanger. Examples of its use are to assist victims of smoke inhalation injury, respiratory failure, and cardiac failure. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extrarenal: Outside of the kidney. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which
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occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibrotic tissue: Inflamed tissue that has become scarred. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] 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] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the
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induction of hypotension in surgery. [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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH]
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Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] 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]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a
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nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycyrrhetinic Acid: 3-beta-Hydroxy-11-oxoolean-12-en-30-oic acid. A product from Glycyrrhiza glabra L. Leguminosae with some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haloperidol: Butyrophenone derivative. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH]
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Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [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] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeodomain Proteins: Proteins encoded by homeobox genes that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (gene expression regulation, developmental). [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [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
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help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaldosteronism: Aldosteronism. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperkalaemia: Pathology: an abnormally high concentration of potassium in the blood. [EU]
Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type
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IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypokalaemia: Abnormally low potassium concentration in the blood; it may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhoea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. [EU] Hypopituitarism: Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FSH; somatotropin; and corticotropin). This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH]
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Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [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] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH]
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Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Investigative Techniques: Investigative techniques used in pre-clinical and clinical research, epidemiology, chemistry, immunology, genetics, etc. They do not include techniques specifically applied to diagnosis; therapeutics; anesthesia and analgesia, surgery, operative, and dentistry. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport
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can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] 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] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH]
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Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH]
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Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Circulation: The circulation of blood through the vessels of the liver. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B
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(with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [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] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU]
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Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: 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] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [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] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH]
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Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU]
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Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myxedema: A condition characterized by a dry, waxy type of swelling with abnormal deposits of mucin in the skin and other tissues. It is produced by a functional insufficiency of the thyroid gland, resulting in deficiency of thyroid hormone. The skin becomes puffy around the eyes and on the cheeks and the face is dull and expressionless with thickened nose and lips. The congenital form of the disease is cretinism. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Natriuretic Hormone: A low-molecular weight substance, possibly from the hypothalamus, which is released due to plasma volume expansion. It causes natriuresis in part by inhibiting sodium potassium ATPase. The development of hypertension may be the consequence of an abnormality in volume regulation induced by a defect in the renal response to the natriuretic effect of the natriuretic hormone. Do not confuse with atrial natriuretic factor or cardionatrin which is a different, well characterized hormone. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal
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agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] 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
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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] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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 pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
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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] Nucleoproteins: Proteins conjugated with nucleic acids. [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] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] 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] 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] Osteodystrophy: Defective bone formation. [EU] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH]
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Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paracentesis: A procedure in which fluid is withdrawn from a body cavity via a trocar and cannula, needle, or other hollow instrument. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU]
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Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the
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mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylephrine: An alpha-adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Apoplexy: Sudden hemorrhage or ischemic necrosis involving the pituitary gland which may be associated with acute visual loss, severe headache, meningeal signs, cranial nerve palsies, panhypopituitarism, and rarely coma. The most common cause is hemorrhage (intracranial hemorrhages) related to a pituitary adenoma. Ischemia, meningitis, intracranial
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hypertension, and other disorders may be associated with this condition. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Neoplasms: Neoplasms which arise from or metastasize to the pituitary gland. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (adenoma, basophil; adenoma, acidophil; and adenoma, chromophobe). Pituitary tumors may compress adjacent structures, including the hypothalamus, several cranial nerves, and the optic chiasm. Chiasmal compression may result in bitemporal hemianopsia. [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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH]
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Polydipsia: Chronic excessive thirst, as in diabetes mellitus or diabetes insipidus. [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] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [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] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potassium Chloride: Potassium chloride. A white crystal or crystalline powder used as an electrolyte replenisher, in the treatment of hypokalemia, in buffer solutions, and in fertilizers and explosives. [NIH] Potassium Compounds: Inorganic compounds that contain potassium as an integral part of the molecule. [NIH] Potassium, Dietary: Potassium or potassium compounds used in foods or as foods. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of
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the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preceptorship: Practical experience in medical and health-related services that occurs as part of an educational program wherein the professionally-trained student works outside the academic environment under the supervision of an established professional in the particular field. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pregnenolone: Steroid hormone. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] 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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Program Development: The process of formulating, improving, and expanding educational,
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managerial, or service-oriented work plans (excluding computer program development). [NIH]
Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prolactinoma: A pituitary adenoma which secretes prolactin, leading to hyperprolactinemia. Clinical manifestations include amenorrhea; galactorrhea; impotence; headache; visual disturbances; and cerebrospinal fluid rhinorrhea. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some
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cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins B: Physiologically active prostaglandins found in many tissues and organs. They are potent pressor substances and have many other physiological activities. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the
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nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudohypoaldosteronism: A hereditary disorder characterized by salt wasting and growth retardation, presenting in infancy as high levels of urinary sodium despite hyponatremia, hyperkalemia, hyperreninemia, and elevated aldosterone levels. The mode of inheritance is probably autosomal dominant, affecting electrolyte secretion in the kidney tubule. [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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
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] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure
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the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Rauwolfia: A genus of the Apocynaceae or dogbane family of tropical trees and shrubs containing alkaloids. These alkaloids have been used as tranquilizers and antihypertensive agents. Reserpine is derived from R. serpentina. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]
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Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal cysts: Abnormal fluid-filled sacs in the kidney that range in size from microscopic to much larger. Many simple cysts are harmless, while other types can seriously damage the kidneys. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal Plasma Flow: The amount of plasma that perfuses the kidneys per unit time, approximately 10% greater than effective renal plasma flow (renal plasma flow, effective). It should be differentiated from the renal blood flow (RBF) which refers to the total volume of blood flowing through the renal vasculature, while the renal plasma flow refers to the rate of plasma flow (RPF). [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.
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Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [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] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] 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] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatoid: Resembling rheumatism. [EU] 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] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is
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deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcosine: Methylamino-acetic acid. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a
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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] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] 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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled
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to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] 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] Smoke Inhalation Injury: Pulmonary injury following the breathing in of toxic smoke from burning materials such as plastics, synthetics, building materials, etc. This injury is the most frequent cause of death in burn patients. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH]
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Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sperm Maturation: Posttesticular ripening of spermatozoa. [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] Splanchnic Circulation: The circulation of blood through the vessels supplying the abdominal viscera. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
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Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subcapsular: Situated below a capsule. [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] Subfornical Organ: A structure, situated close to the intraventricular foramen, which induces drinking behavior after stimulation with angiotensin II. [NIH] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH]
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Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprarenal: Above a kidney. [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] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathectomy: The removal or interruption of some part of the sympathetic nervous system for therapeutic or research purposes. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic heart failure: Inability of the heart to contract with enough force to pump adequate amounts of blood through the body. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH]
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Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] 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] 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] 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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU]
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Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcendental meditation: TM. A mental technique used to promote relaxation, reduce stress, and improve quality of life. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body.
Dictionary 251
Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [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] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urobilinogen: A colorless compound formed in the intestines by the reduction of bilirubin. Some is excreted in the feces where it is oxidized to urobilin. Some is reabsorbed and reexcreted in the bile as bilirubin. At times, it is re-excreted in the urine, where it may be later oxidized to urobilin. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH]
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Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] 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] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU]
Dictionary 253
Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] Void: To urinate, empty the bladder. [NIH] Volition: Voluntary activity without external compulsion. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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] Zona Glomerulosa: The narrow subcapsular outer zone of the adrenal cortex. This zone consists of granular cells which stain deeply and are arranged in rounded groups. It converts pregnenolone to aldosterone by a series of enzymatically regulated steps. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
255
INDEX 1 18-Hydroxycorticosterone, 80, 101, 187 A Abdomen, 187, 196, 220, 223, 232, 242, 247, 251, 252 Abdominal, 187, 188, 225, 231, 232, 233, 241, 242, 246 Abdominal Pain, 187, 233 Ablation, 187, 218 Acceptor, 187, 223, 231 Acetylcholine, 187, 229 Acidosis, 187 Actin, 8, 53, 187, 213, 227 Acute renal, 118, 160, 187 Acute tubular, 158, 187 Acyl, 12, 187 Acylation, 12, 187 Adaptability, 187, 199 Adaptation, 33, 40, 49, 187, 227 Adenine, 187 Adenosine, 33, 44, 187, 197, 233 Adenovirus, 22, 47, 188 Adenylate Cyclase, 80, 188, 212 Adipocytes, 14, 188, 222 Adipose Tissue, 15, 94, 188 Adjustment, 187, 188 Adolescence, 49, 188 Adrenal Cortex, 10, 39, 47, 95, 161, 188, 189, 204, 211, 236, 241, 253 Adrenal Glands, 56, 142, 159, 188, 241 Adrenal insufficiency, 161, 188 Adrenal Medulla, 188, 199, 210, 229 Adrenergic, 30, 38, 61, 76, 96, 99, 156, 188, 190, 192, 193, 194, 207, 210, 225, 233, 237, 248 Adrenergic beta-Antagonists, 188, 192 Adverse Effect, 143, 148, 188, 242, 244 Aerobic, 188, 231 Aerobic Metabolism, 188, 231 Aerobic Respiration, 188, 231 Aerosol, 188, 248 Afferent, 20, 48, 63, 110, 188, 222 Affinity, 51, 188, 189, 245 Agar, 189, 234 Age of Onset, 189, 251 Agonist, 35, 41, 43, 51, 54, 55, 65, 70, 107, 122, 189, 196, 207, 233 Airway, 18, 189, 245
Alanine, 54, 189 Albumin, 30, 189, 225, 234 Aldosterone Antagonists, 76, 104, 108, 122, 130, 136, 144, 146, 147, 151, 153, 155, 189 Alertness, 189, 197 Algorithms, 189, 196 Alkaline, 187, 189, 190, 197, 249 Alkaloid, 189, 196, 241 Alkalosis, 142, 159, 189, 249 Alleles, 75, 189, 222 Allergen, 190, 206 Allograft, 29, 190 Alpha Particles, 190, 239 Alpha-1, 54, 190 Alprenolol, 190, 225 Alternative medicine, 190 Aluminum, 142, 190 Alveolar Process, 190, 242 Ameliorated, 64, 190 Amenorrhea, 190, 196, 237 Amino Acid Sequence, 190, 192 Amino Acid Substitution, 114, 190 Amino Acids, 190, 191, 232, 235, 238, 243, 250, 251 Aminolevulinic Acid, 162, 190 Amlodipine, 86, 190 Ammonia, 46, 190, 248, 251 Amnion, 190 Amniotic Fluid, 85, 107, 190 Amylase, 162, 191 Anaesthesia, 191, 219 Anal, 191, 210 Analog, 7, 67, 191, 206 Analogous, 191, 250 Anaplasia, 191, 228 Anatomical, 47, 191, 194, 200, 203, 206, 219, 232, 243 Androgens, 188, 191 Anemia, 158, 191 Anesthesia, 189, 191, 220 Anesthetics, 191, 210 Aneurysm, 191, 212, 252 Angina, 188, 190, 191, 225, 237 Angina Pectoris, 188, 190, 191, 225, 237 Angiotensin I, 10, 13, 17, 22, 53, 62, 65, 67, 69, 83, 128, 191
256
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Angiotensin-Converting Enzyme Inhibitors, 61, 191, 192 Angiotensinogen, 14, 26, 29, 30, 60, 61, 191, 241 Angiotensins, 15, 66, 191 Animal model, 4, 15, 19, 23, 24, 33, 34, 35, 50, 63, 191 Anions, 189, 192, 221, 244, 247 Annealing, 192, 235 Anomalies, 192, 227 Antagonism, 10, 42, 49, 73, 74, 79, 85, 86, 96, 128, 160, 192, 197 Antiallergic, 192, 215 Antiangiogenic, 20, 192 Antibacterial, 192, 215, 246 Antibiotic, 192, 204, 232, 246, 247 Antibodies, 40, 44, 65, 192, 215, 218, 234 Antibody, 189, 192, 201, 215, 216, 218, 219, 224, 239, 246 Anticoagulant, 192, 238 Antidiuretic, 7, 113, 161, 192, 193, 198, 206, 228 Antiemetic, 192, 193, 225 Antigen, 189, 192, 202, 216, 217, 218, 219, 224, 239 Antihypertensive, 6, 17, 18, 21, 37, 64, 98, 130, 156, 190, 192, 212, 217, 240, 242 Antihypertensive Agents, 37, 156, 192, 240 Anti-inflammatory, 9, 143, 148, 192, 199, 206, 214, 219 Anti-Inflammatory Agents, 192, 199 Antioxidant, 192, 231 Antipsychotic, 193, 242 Antiviral, 193, 215 Anuria, 193, 221 Anus, 191, 193, 201 Aorta, 50, 58, 64, 193, 236, 241, 252 Aortic Coarctation, 33, 193 Apnea, 193 Apnoea, 85, 193 Apoptosis, 33, 56, 193 Aquaporins, 56, 193 Aqueous, 147, 193, 195, 205, 209, 217, 222 Arachidonic Acid, 13, 149, 158, 193, 222, 237 Arginine, 4, 116, 118, 139, 158, 193, 206, 216, 229 Argipressin, 193, 206 Arteries, 30, 47, 65, 102, 193, 194, 196, 198, 199, 204, 223, 227, 249 Arteriolar, 32, 194, 196, 241
Arterioles, 32, 33, 65, 110, 194, 196, 197, 226, 251 Arteriovenous, 194, 226 Artery, 11, 50, 58, 191, 193, 194, 198, 204, 206, 239 Ascites, 4, 69, 145, 157, 194 Ascitic Fluid, 158, 194 Assay, 105, 194, 239 Asymptomatic, 102, 110, 194 Atenolol, 103, 194 Atrial, 7, 79, 86, 89, 100, 108, 113, 114, 118, 119, 130, 131, 158, 160, 194, 203, 227 Atrium, 194, 203, 252 Atrophy, 194, 228 Attenuated, 24, 34, 48, 194, 207 Attenuation, 48, 67, 194 Autacoids, 194, 219 Autoimmune disease, 194 Autoimmunity, 82, 194 Autonomic Nervous System, 38, 194, 232, 245, 248 Autoradiography, 34, 194 Axons, 194, 230, 242 B Bacteria, 187, 192, 194, 195, 203, 211, 212, 217, 225, 226, 240, 244, 246, 250, 251 Bacterial Physiology, 187, 194 Bacterium, 195, 203 Baroreflex, 38, 45, 195 Base, 8, 26, 43, 53, 158, 159, 187, 189, 195, 205, 221, 248 Basement Membrane, 195, 211 Bed Rest, 20, 195 Benign, 66, 67, 89, 101, 187, 195, 215, 228 Bewilderment, 195, 203 Bilateral, 76, 110, 195 Bile, 195, 216, 217, 221, 223, 246, 251 Bile Pigments, 195, 221 Bilirubin, 162, 189, 195, 217, 251 Binding Sites, 33, 51, 133, 195 Bioavailability, 152, 195 Biological therapy, 195, 215 Biological Transport, 195, 206 Biomarkers, 11, 23, 195 Biopsy, 4, 195 Biotechnology, 66, 73, 169, 196 Biotinylation, 40, 196 Bladder, 6, 68, 70, 71, 131, 196, 202, 219, 228, 238, 241, 251, 253 Blood Coagulation, 196, 197, 249 Blood Glucose, 4, 196, 216, 220
257
Blood vessel, 192, 195, 196, 198, 200, 203, 209, 214, 223, 225, 232, 241, 245, 247, 249, 251, 252 Blood Volume, 20, 58, 161, 196 Blot, 54, 61, 196 Body Fluids, 189, 195, 196, 208, 245, 250 Body Mass Index, 196, 231 Bone Marrow, 25, 161, 196, 210, 213, 223 Bone scan, 196, 243 Bowel, 191, 196, 220, 222, 232, 247 Brachial, 11, 196 Bradykinin, 15, 59, 65, 196, 221, 229, 234 Bromocriptine, 75, 196 Bronchi, 197, 210, 250 Buffers, 46, 195, 197 C Caffeine, 139, 197 Calcitonin, 16, 122, 197 Calcium Channel Blockers, 192, 197 Calmodulin, 54, 79, 111, 197 Cannula, 197, 231 Canrenoate Potassium, 86, 197 Capillary, 47, 196, 197, 214, 252 Capillary Permeability, 196, 197 Capsules, 146, 151, 197, 214 Captopril, 12, 197 Carbenoxolone, 129, 132, 135, 198 Carbohydrate, 198, 214 Carboxymethylcellulose, 147, 198 Carcinogenic, 198, 220, 237, 246 Carcinogens, 198, 231 Carcinoma, 95, 159, 198 Cardiac Output, 45, 162, 195, 198, 247 Cardiology, 11, 73, 75, 80, 85, 86, 88, 90, 96, 97, 98, 99, 100, 105, 114, 122, 198 Cardiomyopathy, 56, 145, 148, 152, 198 Cardioselective, 194, 198, 237 Cardiotonic, 198, 206, 233 Cardiovascular, 9, 15, 16, 17, 18, 19, 20, 26, 28, 30, 31, 33, 34, 35, 37, 48, 51, 55, 57, 59, 62, 75, 79, 87, 91, 97, 99, 103, 104, 105, 109, 118, 134, 136, 143, 145, 148, 149, 151, 153, 156, 198, 222, 244, 245 Cardiovascular Physiology, 59, 198 Cardiovascular System, 9, 97, 104, 149, 198 Carotene, 198, 242 Carotid Arteries, 30, 198 Carrier Proteins, 198, 234, 240 Case report, 199, 201 Case series, 199, 201 Catalytic Domain, 90, 199
Catecholamine, 122, 199, 207 Cations, 199, 221 Causal, 199, 210 Celecoxib, 50, 199 Cell Cycle, 4, 199 Cell Death, 62, 193, 199, 228 Cell Differentiation, 199, 244 Cell Division, 194, 199, 215, 226, 234, 237, 244 Cell membrane, 79, 88, 106, 195, 197, 199, 205, 220, 221, 233, 235, 245 Cell proliferation, 199, 244 Cell Respiration, 188, 199, 231, 242 Cell Survival, 57, 154, 199, 215 Cerebral, 11, 27, 31, 33, 199, 200, 203, 210, 211 Cerebral Arteries, 33, 199 Cerebral Cortex, 199, 211 Cerebrospinal, 200, 237 Cerebrospinal fluid, 200, 237 Cerebrovascular, 197, 198, 200 Cerebrum, 199, 200 Character, 4, 147, 191, 200 Chemotherapy, 57, 200 Chiasma, 200, 204 Chimeras, 58, 200 Chin, 78, 123, 139, 200, 225 Cholesterol, 14, 84, 195, 200, 204, 208, 217, 223, 246 Choroid, 200, 242 Chromaffin System, 200, 209 Chromatin, 43, 193, 200, 223, 229, 246 Chromosomal, 27, 36, 200, 213, 216 Chromosome, 82, 95, 200, 203, 215, 222, 244 Chronic renal, 23, 88, 118, 158, 200, 234 Circadian, 7, 67, 80, 129, 200 Circadian Rhythm, 7, 67, 200 Circulatory system, 200, 209 Cirrhosis, 4, 69, 145, 146, 151, 157, 200, 235 CIS, 27, 39, 201, 242 Clamp, 52, 55, 59, 201 Clinical Medicine, 43, 88, 112, 201, 236 Clinical study, 47, 201, 203 Clinical trial, 8, 19, 35, 50, 105, 169, 201, 203, 207, 227, 238, 240 Cloning, 13, 43, 196, 201, 222 Coenzyme, 21, 201 Cofactor, 201, 238, 249 Cohort Studies, 201, 210 Collagen, 9, 61, 115, 146, 155, 195, 201, 211, 212, 224, 234, 237
258
Aldosterone
Collapse, 201, 245 Colloidal, 189, 201, 244, 248 Colon, 18, 26, 42, 69, 151, 201, 222 Combination Therapy, 49, 143, 145, 149, 152, 201 Combinatorial, 22, 201 Complement, 201, 202, 213, 224, 234 Complementary and alternative medicine, 127, 137, 202 Complementary medicine, 127, 202 Compliance, 17, 19, 21, 202 Computational Biology, 169, 202 Computed tomography, 202, 243 Computer Simulation, 16, 202 Computerized axial tomography, 202, 243 Conception, 202, 212 Cones, 202, 242 Confusion, 155, 203, 207, 251 Conjugated, 203, 205, 227, 229, 230, 243 Conjugation, 67, 203 Connective Tissue, 196, 201, 203, 205, 212, 221, 225 Constipation, 193, 203, 233 Constriction, 203, 252 Constriction, Pathologic, 203, 252 Contractility, 191, 203 Contraindications, ii, 203 Control group, 203, 236, 240 Controlled clinical trial, 20, 203 Convulsions, 203, 208, 236 Cor, 203, 218 Coronary, 33, 40, 153, 191, 198, 204, 227 Coronary heart disease, 153, 198, 204 Coronary Thrombosis, 204, 227 Corpus, 204, 223, 236, 253 Corpus Luteum, 204, 223, 236 Cortex, 10, 39, 47, 58, 204 Cortical, 24, 26, 40, 43, 44, 70, 72, 96, 131, 145, 152, 204 Corticosteroids, 56, 57, 71, 143, 148, 204, 214, 226 Cortisone, 204, 206 Cranial, 204, 215, 230, 232, 233, 234, 251 Creatinine, 5, 21, 22, 30, 50, 162, 204, 221 Creatinine clearance, 162, 204 Crossing-over, 115, 204, 240 Cross-Sectional Studies, 204, 210 Cultured cells, 42, 204 Cyclic, 47, 188, 193, 197, 204, 212, 215, 229, 237 Cycloheximide, 10, 204 Cyst, 19, 21, 49, 50, 162, 205
Cytochrome, 47, 91, 205 Cytokine, 9, 22, 23, 205 Cytoplasm, 193, 199, 205, 209, 215, 223, 243 Cytoprotection, 57, 205 Cytoskeleton, 53, 205 Cytotoxic, 205, 245 D Deamination, 205, 251 Decompensation, 19, 205 Decongestant, 205, 233 Deletion, 44, 82, 99, 193, 205, 213 Denaturation, 205, 235 Dendrites, 205, 228 Deoxyribonucleic, 89, 205, 243 Deoxyribonucleic acid, 89, 205, 243 Deoxyribonucleotides, 205 Depolarization, 205, 245 Depressive Disorder, 205, 223 Deprivation, 27, 55, 205 Dermis, 205, 248 Desensitization, 51, 206 Desmopressin, 7, 206 Deuterium, 206, 217 Dexamethasone, 82, 132, 145, 206 Diabetes Insipidus, 162, 193, 206, 235 Diabetes Mellitus, 3, 4, 77, 79, 104, 158, 162, 206, 214, 216, 235 Diabetic Retinopathy, 154, 206 Diagnostic procedure, 141, 206 Diarrhoea, 206, 218 Diastole, 206 Diastolic, 9, 98, 108, 153, 206, 217 Diastolic blood pressure, 153, 206 Diffusion, 46, 195, 197, 206, 207, 219, 221 Digestion, 195, 196, 206, 220, 223, 247, 251 Digestive tract, 198, 206, 245 Digitalis, 7, 206, 230 Dihydrotestosterone, 206, 240 Dihydroxy, 189, 206, 211 Dilatation, Pathologic, 206, 252 Dilated cardiomyopathy, 56, 206 Dilation, 196, 206, 252 Dilution, 158, 207, 210, 234 Dimerization, 10, 207 Diploid, 207, 234 Direct, iii, 4, 11, 16, 30, 34, 37, 40, 44, 45, 46, 51, 52, 60, 88, 127, 144, 201, 207, 217, 241, 248 Disease Progression, 5, 50, 207 Disorientation, 155, 203, 207 Dissociation, 188, 207
259
Distal, 5, 8, 18, 19, 24, 26, 41, 42, 58, 68, 69, 113, 145, 152, 161, 184, 207, 208, 239 Diuresis, 20, 56, 66, 160, 197, 207 Diuretic, 4, 5, 19, 37, 65, 76, 81, 100, 144, 147, 150, 207 Diuretics, Thiazide, 76, 192, 207 Diurnal, 83, 148, 159, 207 Dominance, 207, 210 Dopamine, 67, 127, 162, 193, 196, 207, 225, 229, 233 Double-blind, 50, 207 Double-blinded, 50, 207 Drinking Behavior, 207, 247 Drive, ii, vi, 7, 15, 16, 19, 30, 37, 121, 162, 208, 221 Drug Tolerance, 208, 249 Duct, 18, 23, 24, 27, 41, 43, 44, 46, 51, 72, 162, 197, 208, 243, 248, 251 Dyslipidemia, 149, 208 Dyspnea, 205, 208 E Echocardiography, 61, 208 Eclampsia, 208, 236 Edema, 73, 144, 154, 161, 183, 205, 206, 208, 228, 236 Effector, 34, 41, 52, 62, 187, 201, 208 Efferent, 63, 208 Efficacy, 33, 49, 50, 87, 104, 144, 208 Elastin, 201, 208, 211 Elective, 112, 208 Electrode, 8, 36, 59, 208 Electron microscope, 105, 208 Electrons, 193, 195, 208, 221, 231, 239 Elementary Particles, 208, 229, 238 Embryo, 190, 199, 209, 219, 236 Emulsion, 194, 209 Endocrine Glands, 209, 232 Endocrine System, 160, 209 Endocytosis, 58, 209 Endogenous, 9, 27, 32, 44, 47, 54, 59, 64, 149, 153, 207, 209, 231, 238, 250 Endothelial cell, 39, 47, 51, 111, 209, 249 Endothelium, 7, 28, 31, 32, 209, 229 Endothelium, Lymphatic, 209 Endothelium, Vascular, 209 Endothelium-derived, 209, 229 Endotoxins, 202, 209, 221 End-stage renal, 19, 50, 92, 118, 200, 209, 234 Energy balance, 209, 222 Enhancer, 27, 39, 210, 242 Environmental Health, 168, 170, 210
Enzymatic, 32, 142, 197, 198, 199, 202, 210, 212, 235, 242 Enzyme Inhibitors, 9, 210, 234 Epidemiologic Studies, 26, 145, 210 Epidermal, 51, 95, 210 Epidermal Growth Factor, 51, 95, 210 Epidermal growth factor receptor, 95, 210 Epidermis, 205, 210 Epinephrine, 112, 160, 162, 188, 207, 210, 229, 251 Epistasis, 28, 210 Epithelial Cells, 8, 18, 52, 53, 69, 131, 145, 152, 210, 226 Epithelium, 68, 195, 209, 210 Ergot, 196, 210 Erythrocyte Volume, 196, 210 Erythrocytes, 191, 196, 210, 240 Erythropoietin, 158, 161, 210 Estradiol, 18, 57, 72, 211 Estriol, 72, 162, 211 Estrogen, 24, 34, 57, 211, 237, 244 Estrogen receptor, 34, 211 Ether, 142, 211 Ethylene Glycol, 142, 211 Eukaryotic Cells, 211, 219, 251 Evoke, 211, 247 Excrete, 193, 211, 221, 241 Exhaustion, 192, 211 Exogenous, 35, 47, 198, 209, 211, 238, 251 Extracellular Matrix, 4, 9, 21, 112, 154, 203, 211, 212, 224 Extracellular Matrix Proteins, 211, 224 Extracellular Space, 64, 211 Extracorporeal, 113, 211 Extracorporeal Membrane Oxygenation, 113, 211 Extrapyramidal, 193, 207, 211 Extrarenal, 55, 211 Eye Infections, 188, 211 F Family Planning, 169, 212 Fat, 14, 30, 40, 188, 193, 196, 198, 203, 204, 212, 222, 231, 245, 250 Fatigue, 212, 215 Fatty acids, 48, 88, 189, 212, 237, 249 Feces, 203, 212, 247, 251 Fertilizers, 212, 229, 235 Fetus, 57, 85, 210, 212, 234, 236, 251 Fibrin, 196, 212, 233, 249 Fibrinolytic, 27, 31, 212 Fibroblasts, 21, 61, 212
260
Aldosterone
Fibrosis, 9, 10, 21, 25, 29, 61, 83, 89, 98, 146, 155, 212, 243 Fibrotic tissue, 146, 155, 212 Filtration, 49, 212, 221 Fluorescence, 53, 212 Fold, 42, 212, 225 Foramen, 200, 212, 232, 247 Forearm, 102, 110, 196, 212 Forskolin, 107, 212 G Ganglia, 187, 193, 212, 228, 232, 248 Ganglionic Blockers, 192, 212 Gas, 190, 206, 213, 217, 229, 242, 247, 248 Gastric, 44, 210, 213 Gastrin, 213, 216 Gastrointestinal, 149, 158, 196, 210, 213, 218, 222, 244, 245, 247, 251 Gastrointestinal tract, 149, 213, 222, 244, 251 Gelsolin, 8, 213 Gene Deletion, 9, 213 Gene Duplication, 75, 144, 213 Gene Expression, 14, 27, 40, 63, 213, 216, 245 Gene Therapy, 17, 188, 213 Genetic Engineering, 196, 201, 213 Genetic Techniques, 61, 213 Genetic testing, 213, 235 Genetics, 3, 17, 27, 29, 30, 31, 36, 59, 91, 101, 104, 105, 203, 207, 213, 220 Genomics, 17, 18, 57, 62, 213 Genotype, 29, 60, 88, 93, 213, 233 Geriatric, 56, 213 Germ Cells, 213, 230, 231, 246, 248 Gestation, 26, 214, 232, 234 Glomerular, 4, 5, 93, 134, 162, 214, 220, 221, 241 Glomerular Filtration Rate, 5, 214, 221 Glomerulus, 214 Glucocorticoid, 23, 36, 42, 52, 57, 69, 75, 82, 144, 145, 206, 214, 226 Glucose, 3, 30, 40, 55, 68, 93, 123, 162, 196, 206, 214, 215, 216, 220, 240, 243 Glucose Intolerance, 206, 214 Glucose tolerance, 3, 214 Glucose Tolerance Test, 214 Glucuronic Acid, 214, 216 Glutamic Acid, 214, 229, 237 Glycerol, 193, 214, 233 Glycine, 190, 214, 229 Glycoprotein, 132, 134, 210, 214, 249 Glycoside, 214, 230, 243
Glycyrrhetinic Acid, 130, 215 Goiter, 162, 215 Gonadal, 215, 246 Governing Board, 215, 236 Grade, 32, 215 Graft, 83, 215, 219 Granulocytes, 215, 222, 245, 253 Growth factors, 22, 29, 33, 53, 215 Guanine, 61, 93, 215 Guanylate Cyclase, 215, 229 H Habitual, 200, 215 Haloperidol, 98, 215 Haploid, 215, 234 Haplotypes, 60, 94, 215 Haptens, 189, 215, 240 Headache, 197, 215, 233, 237 Heart attack, 145, 198, 215 Hemodialysis, 161, 215, 221 Hemodynamics, 34, 45, 86, 162, 216 Hemoglobin, 162, 191, 210, 216 Hemoglobinopathies, 213, 216 Hemorrhage, 206, 215, 216, 233, 247 Heparin, 94, 116, 216 Hepatic, 67, 157, 189, 214, 216, 223 Hepatorenal Syndrome, 4, 80, 114, 158, 216 Hereditary, 94, 216, 228, 239 Heredity, 213, 216 Heterodimer, 25, 216 Heterogeneity, 60, 189, 216 Histones, 200, 216 Homeobox, 216 Homeodomain Proteins, 10, 216 Homeostasis, 10, 16, 18, 23, 35, 41, 44, 53, 55, 58, 59, 61, 62, 63, 151, 158, 160, 161, 216, 245 Homologous, 51, 189, 204, 213, 216, 244, 248 Hormonal, 6, 8, 17, 31, 37, 45, 52, 56, 114, 194, 216 Human growth hormone, 78, 217 Humoral, 20, 21, 217 Humour, 217 Hybrid, 36, 43, 82, 217 Hydralazine, 136, 217 Hydrogen, 123, 146, 150, 161, 187, 195, 197, 198, 205, 206, 211, 217, 223, 226, 229, 231, 239, 247 Hydrogen Peroxide, 217, 223, 247 Hydrolysis, 54, 217, 221, 233, 235, 238 Hydroxylysine, 201, 217
261
Hydroxyproline, 201, 217 Hyperaldosteronism, 77, 88, 91, 97, 102, 116, 142, 143, 146, 147, 151, 217 Hyperbilirubinemia, 217, 221 Hypercholesterolemia, 208, 217 Hyperglycemia, 3, 38, 217 Hyperkalaemia, 76, 217 Hyperlipidemia, 208, 217 Hyperplasia, 6, 68, 82, 107, 115, 144, 159, 217 Hypersecretion, 115, 143, 162, 217 Hypersensitivity, 27, 44, 190, 206, 217, 222 Hypertriglyceridemia, 208, 217 Hypertrophic cardiomyopathy, 92, 218 Hypertrophy, 9, 15, 23, 49, 54, 87, 92, 102, 103, 114, 117, 145, 146, 152, 155, 204, 217, 218 Hypnotic, 133, 218 Hypokalaemia, 130, 218 Hypopituitarism, 162, 218 Hypotension, 57, 193, 203, 213, 218 Hypotensive, 57, 218, 221 Hypothalamic, 45, 218, 245 Hypothalamus, 194, 218, 227, 234 Hypovolemia, 162, 218 Hypoxia, 49, 90, 97, 218 Hypoxic, 49, 218 I Idiopathic, 6, 91, 93, 97, 116, 144, 159, 218 Imidazole, 152, 218 Immersion, 118, 119, 218 Immune response, 29, 56, 192, 194, 204, 215, 218, 224, 247, 252 Immune system, 194, 195, 218, 219, 222, 224, 233, 251, 253 Immunity, 189, 218, 224 Immunofluorescence, 38, 218 Immunogenic, 218, 240 Immunohistochemistry, 32, 58, 218 Immunologic, 218, 224 Immunology, 189, 219, 220 Immunosuppressive, 214, 219 Immunotherapy, 195, 206, 219 Impairment, 22, 122, 157, 158, 195, 212, 219 Impotence, 219, 237 In situ, 8, 47, 133, 219 In Situ Hybridization, 8, 219 In vitro, 10, 27, 39, 46, 47, 49, 51, 57, 61, 70, 76, 98, 131, 133, 135, 213, 219, 235
In vivo, 9, 12, 26, 27, 44, 46, 47, 51, 55, 57, 59, 61, 64, 90, 101, 122, 213, 216, 219, 231, 249 Incontinence, 7, 219 Incubation, 47, 219 Indomethacin, 85, 137, 219 Induction, 25, 27, 54, 70, 98, 191, 193, 213, 219, 237 Infancy, 219, 239 Infarction, 87, 218, 219 Infection, 158, 195, 211, 219, 223, 232, 247, 253 Infertility, 196, 219 Infiltration, 9, 25, 219 Inflammation, 15, 21, 62, 143, 148, 149, 189, 192, 212, 215, 219, 222, 227, 233, 234, 238, 252 Infusion, 10, 25, 40, 55, 58, 135, 220 Ingestion, 20, 128, 139, 214, 220, 249 Initiation, 61, 162, 220, 237, 247, 250 Inositol, 52, 220 Inotropic, 194, 207, 220 Insight, 10, 64, 220 Insulin, 24, 30, 39, 54, 88, 93, 99, 118, 123, 128, 134, 160, 214, 220, 251 Insulin-dependent diabetes mellitus, 93, 134, 220 Intermittent, 220, 223 Internal Medicine, 5, 23, 26, 31, 42, 46, 58, 104, 113, 209, 220, 228 Interstitial, 6, 25, 46, 211, 220, 241 Intestinal, 27, 198, 214, 220 Intestine, 123, 196, 220, 222 Intoxication, 134, 220, 253 Intracellular, 8, 13, 14, 21, 42, 48, 56, 58, 75, 197, 213, 219, 220, 229, 235, 237, 244 Intrahepatic, 100, 220 Intraocular, 154, 212, 220, 230 Intraocular pressure, 154, 212, 220, 230 Intravascular, 160, 220 Intravenous, 38, 86, 135, 220 Intrinsic, 63, 143, 189, 193, 195, 220 Inulin, 214, 220 Investigative Techniques, 17, 220 Involuntary, 7, 220, 227, 241 Ion Transport, 46, 52, 53, 220, 226 Ions, 142, 154, 195, 197, 207, 208, 213, 217, 220, 221, 235, 245 Irrigation, 55, 221 Isotonic, 118, 221, 226 J Jaundice, 158, 216, 217, 221
262
Aldosterone
K Kallidin, 196, 221 Kb, 60, 168, 221 Keto, 87, 221 Kidney Disease, 4, 5, 19, 21, 22, 49, 50, 60, 101, 115, 160, 168, 221 Kidney Failure, 161, 209, 221 Kidney Failure, Acute, 221 Kidney Failure, Chronic, 221 Kidney Glomerulus, 4, 221 Kidney stone, 162, 221, 241, 251 Kidney Transplantation, 82, 158, 221, 222 Kinetics, 68, 104, 222 L Lactation, 26, 222, 237 Large Intestine, 206, 220, 222, 240, 245 Latency, 25, 222 Latent, 68, 222, 236 Laxative, 189, 198, 222, 225 Lens, 193, 222, 253 Leptin, 30, 48, 222 Lesion, 30, 222, 223 Lethal, 50, 222 Leucocyte, 190, 222 Leukemia, 213, 222 Leukotrienes, 88, 193, 222 Life Expectancy, 19, 222 Ligaments, 204, 222 Ligands, 27, 63, 222 Ligase, 52, 222 Linkage, 28, 30, 44, 57, 60, 222 Linkage Disequilibrium, 60, 222 Lipid, 4, 18, 52, 197, 214, 220, 221, 222, 223, 231, 250 Lipid Peroxidation, 223, 231 Lipoprotein, 208, 223 Lisinopril, 5, 50, 223 Lithium, 13, 142, 193, 223 Liver Circulation, 158, 223 Liver Cirrhosis, 86, 147, 155, 216, 223 Liver scan, 223, 243 Liver Transplantation, 158, 223 Lobe, 217, 223 Localization, 15, 18, 42, 43, 51, 90, 103, 109, 218, 223 Localized, 18, 219, 223, 234 Long-Term Care, 11, 223 Loop, 19, 76, 161, 223 Low-density lipoprotein, 208, 223 Lumbar, 46, 223 Lutein Cells, 223, 237 Lymph, 200, 209, 217, 223, 247
Lymphatic, 209, 219, 223, 225 Lymphocytes, 88, 118, 133, 192, 222, 223, 224, 253 Lymphoid, 192, 204, 222, 223, 224 Lymphokines, 224 M Macrophage, 9, 25, 224 Macrophage Activation, 9, 224 Macula, 224 Macula Lutea, 224 Macular Degeneration, 154, 224 Magnetic Resonance Imaging, 224, 243 Major Histocompatibility Complex, 215, 224 Malignant, 89, 224, 228 Malnutrition, 189, 194, 224 Mandible, 190, 200, 224, 242 Manic, 193, 223, 224 Matrix metalloproteinase, 154, 224 Medial, 11, 224, 230 Mediate, 23, 42, 58, 61, 88, 207, 224 Mediator, 23, 30, 63, 224, 244 Medical Staff, 207, 225 Medicament, 148, 225 MEDLINE, 7, 169, 225 Medullary, 6, 24, 27, 46, 53, 56, 225 Melanin, 225, 233, 251 Membrane Glycoproteins, 225 Memory, 155, 225 Meninges, 199, 225 Menopause, 18, 79, 225, 235, 236, 237 Menstrual Cycle, 225, 236 Menstruation, 190, 225 Mental, iv, 7, 156, 168, 170, 200, 203, 207, 212, 225, 239, 243, 250, 251 Mental Health, iv, 7, 168, 170, 225, 239 Mesenchymal, 25, 210, 225 Mesenteric, 50, 58, 66, 225, 235 Mesentery, 225, 233, 246 Metabolic acidosis, 158, 225 Metabolic disorder, 206, 225 Metabolite, 59, 211, 225, 236, 240 Metastasis, 224, 225, 228 Metastatic, 128, 218, 225 Methylcellulose, 147, 225 Metoclopramide, 75, 86, 109, 119, 225 Metoprolol, 85, 225 Microbe, 226, 250 Microbiology, 187, 226 Microcirculation, 66, 223, 226 Microorganism, 201, 226, 232, 253 Microscopy, 8, 43, 53, 105, 195, 226
263
Migration, 21, 224, 226 Mitochondrial Swelling, 226, 228 Mitosis, 193, 226, 245 Modification, 213, 226, 239 Modulator, 42, 64, 226 Molecular, 8, 9, 15, 17, 23, 26, 27, 31, 32, 33, 36, 37, 39, 42, 43, 44, 51, 53, 56, 58, 61, 63, 82, 83, 85, 89, 90, 93, 95, 98, 105, 106, 107, 111, 114, 116, 127, 133, 169, 171, 196, 197, 202, 216, 221, 226, 227, 237, 247, 250 Monitor, 24, 40, 204, 226, 229 Mononuclear, 130, 226 Morphogenesis, 216, 226 Morphological, 33, 123, 209, 226 Morphology, 33, 155, 224, 226 Motility, 8, 213, 219, 226, 244 Mucosa, 227, 237 Multicenter Studies, 22, 227 Multicenter study, 227 Multidrug resistance, 134, 227 Muscle Fibers, 131, 135, 227 Mutagenesis, 10, 42, 43, 227 Mutagens, 227 Mydriatic, 207, 227, 233 Myocardial infarction, 9, 15, 27, 31, 74, 87, 100, 109, 113, 139, 145, 152, 204, 227, 237, 252 Myocarditis, 148, 227 Myocardium, 191, 227 Myoglobin, 162, 227 Myosin, 92, 227 Myxedema, 162, 227 N Natriuresis, 20, 66, 134, 160, 191, 227 Natriuretic Hormone, 7, 227 Nausea, 192, 193, 227, 251 NCI, 1, 39, 95, 103, 134, 167, 201, 227 Necrosis, 158, 193, 219, 227, 228, 233 Neonatal, 15, 22, 26, 49, 228 Neoplasms, 89, 198, 228, 234 Nephrogenic, 26, 228 Nephrology, 4, 7, 29, 36, 75, 81, 96, 105, 106, 118, 123, 130, 160, 228 Nephron, 7, 18, 19, 24, 26, 41, 56, 58, 68, 86, 112, 113, 128, 145, 152, 214, 228 Nephropathy, 3, 4, 5, 35, 54, 62, 91, 221, 228 Nephrosis, 216, 228 Nephrotic, 161, 228 Nephrotic Syndrome, 161, 228
Nervous System, 14, 20, 45, 187, 188, 189, 194, 195, 197, 199, 208, 212, 214, 215, 222, 224, 228, 230, 232, 244, 248 Neural, 20, 45, 188, 212, 217, 228, 245 Neurodegenerative Diseases, 48, 228 Neurogenic, 45, 228 Neuromuscular, 55, 187, 218, 228 Neuronal, 228 Neurons, 32, 37, 45, 205, 212, 228, 248 Neuropeptides, 90, 228 Neurosecretory Systems, 209, 228 Neurotransmitter, 187, 188, 196, 207, 214, 228, 229, 244, 247 Neutralization, 65, 229 Neutrons, 190, 229, 239 Neutrophil, 12, 229 Nitrates, 58, 229 Nitric acid, 229 Nitric Oxide, 7, 12, 24, 30, 32, 33, 38, 47, 48, 51, 57, 61, 65, 158, 229 Nitrogen, 26, 189, 191, 211, 221, 229, 250 Norepinephrine, 45, 69, 111, 160, 162, 188, 207, 229, 242 Normotensive, 28, 35, 47, 64, 76, 77, 78, 97, 129, 229 Nuclear, 15, 22, 27, 36, 41, 43, 62, 63, 203, 208, 211, 228, 229, 242 Nuclear Matrix, 43, 229 Nuclear Pore, 229 Nuclear Proteins, 27, 229 Nuclei, 190, 203, 208, 213, 216, 224, 226, 229, 230, 239 Nucleic acid, 219, 227, 229, 230, 242 Nucleoproteins, 229, 230 Nucleus, 43, 62, 193, 200, 204, 205, 206, 209, 211, 223, 226, 229, 230, 237, 239, 245, 247 O Ocular, 154, 230 Ocular Hypertension, 154, 230 Oliguria, 221, 230 Oocytes, 36, 41, 42, 59, 230 Operon, 230, 237, 241 Ophthalmic, 153, 154, 230 Opsin, 230, 242 Optic Chiasm, 218, 230, 234 Optic Disk, 206, 224, 230 Optic Nerve, 154, 230, 242 Osmotic, 189, 226, 230, 244 Osteoclasts, 197, 230 Osteodystrophy, 158, 230 Ouabain, 43, 46, 108, 230
264
Aldosterone
Ovary, 95, 204, 211, 231 Overexpress, 12, 231 Overweight, 47, 124, 231 Ovulation, 83, 231 Ovum, 204, 214, 231, 236, 237, 253 Oxidants, 65, 231 Oxidation, 68, 187, 193, 205, 223, 231 Oxidation-Reduction, 231 Oxidative metabolism, 97, 188, 222, 231 Oxidative Stress, 12, 48, 64, 65, 231 Oxygenase, 32, 64, 231 Oxygenator, 211, 231 P Pancreas, 187, 195, 220, 231, 246, 251 Paracentesis, 158, 231 Paralysis, 218, 231 Parathyroid, 100, 160, 161, 231, 232, 249 Parathyroid Glands, 231, 232 Parathyroid hormone, 100, 160, 161, 232 Parenchyma, 32, 232 Particle, 232, 250 Parturition, 232, 237 Patch, 52, 59, 232 Pathogen, 219, 232 Pathologic, 5, 149, 187, 193, 195, 204, 217, 232, 242 Pathologic Processes, 193, 232 Pathologies, 32, 232 Pathophysiology, 4, 6, 7, 8, 17, 19, 28, 29, 35, 37, 48, 56, 58, 76, 97, 153, 158, 232 Pelvis, 187, 223, 232, 251 Penicillin, 192, 232 Perception, 7, 64, 232, 243 Perfusion, 10, 61, 218, 232 Perinatal, 49, 232 Peripheral Nervous System, 228, 232, 247 Peritoneal, 194, 232 Peritoneal Cavity, 194, 232 Peritoneum, 225, 232, 233, 242 Peritonitis, 158, 233 Phagocyte, 231, 233 Pharmacodynamic, 19, 233 Pharmacologic, 6, 34, 61, 63, 127, 191, 194, 233, 250 Phenotype, 14, 21, 28, 60, 61, 62, 75, 93, 122, 213, 233 Phenyl, 152, 233 Phenylalanine, 233, 251 Phenylephrine, 57, 233 Phosphates, 162, 233 Phospholipases, 233, 244 Phospholipids, 212, 220, 223, 233
Phosphorus, 161, 197, 232, 233 Phosphorylated, 23, 201, 233 Phosphorylates, 23, 42, 233 Phosphorylation, 23, 42, 44, 48, 54, 58, 62, 134, 233 Physiologic, 5, 16, 28, 30, 34, 42, 53, 160, 189, 196, 220, 221, 225, 233, 237, 240, 242 Pigment, 195, 227, 233 Pilot study, 20, 50, 233 Pituitary Apoplexy, 218, 233 Pituitary Gland, 212, 218, 233, 234 Pituitary Neoplasms, 218, 234 Placenta, 211, 234, 236 Plants, 189, 206, 214, 220, 226, 229, 230, 234, 243, 250 Plaque, 143, 234 Plasma cells, 192, 234 Plasma protein, 189, 209, 234, 244 Plasma Volume, 20, 85, 89, 116, 196, 226, 227, 234 Platelet Activation, 234, 245 Platelet Aggregation, 212, 229, 234, 249 Platelets, 229, 234, 244 Ploidy, 89, 234 Pneumonia, 203, 234 Polycystic, 19, 21, 22, 49, 50, 234 Polydipsia, 142, 235 Polymerase, 82, 235, 237, 241 Polymerase Chain Reaction, 82, 235 Polymorphic, 92, 235 Polymorphism, 36, 48, 75, 91, 99, 100, 101, 235 Polypeptide, 190, 201, 210, 227, 235, 237, 253 Polyuria, 6, 142, 158, 235 Portal Hypertension, 158, 235 Portal Vein, 55, 235 Postmenopausal, 18, 235 Postnatal, 49, 235, 246 Postoperative, 158, 235 Postsynaptic, 235, 244 Post-translational, 18, 235 Postural, 69, 159, 235 Potassium Channels, 107, 235 Potassium Chloride, 132, 235 Potassium Compounds, 235 Potassium, Dietary, 158, 235 Potentiation, 65, 235, 245 Practice Guidelines, 170, 236 Preceptorship, 29, 236 Preclinical, 11, 82, 236
265
Precursor, 191, 193, 207, 208, 210, 229, 233, 236, 250, 251 Predisposition, 32, 78, 236 Preeclampsia, 103, 236 Pregnenolone, 137, 236, 253 Premenopausal, 18, 236 Prenatal, 85, 107, 209, 236 Prenatal Diagnosis, 85, 107, 236 Pressoreceptors, 195, 236 Prevalence, 3, 35, 41, 84, 95, 110, 236 Primary endpoint, 22, 236 Probe, 60, 64, 236 Prodrug, 236, 240 Progeny, 203, 236 Progesterone, 41, 57, 85, 132, 142, 151, 236, 237, 246 Progestogen, 83, 236 Program Development, 11, 236 Progression, 3, 4, 5, 7, 20, 21, 22, 40, 49, 50, 61, 100, 150, 191, 237 Progressive, 4, 19, 50, 56, 199, 200, 208, 221, 228, 234, 237, 241 Progressive disease, 50, 237 Projection, 229, 230, 237 Prolactin, 131, 135, 196, 237 Prolactinoma, 75, 237 Proline, 9, 201, 217, 237 Promoter, 27, 42, 44, 52, 103, 109, 237 Promotor, 237, 242 Prone, 14, 122, 237 Prophase, 230, 237, 248 Prophylaxis, 149, 152, 153, 158, 237 Propranolol, 194, 237 Prostaglandin, 4, 67, 85, 143, 148, 191, 237, 249 Prostaglandins A, 66, 219, 237, 238 Prostaglandins B, 148, 238 Prostaglandins D, 238 Prostaglandins F, 238 Prostate, 195, 238, 251 Protease, 35, 201, 238 Protein Binding, 10, 238 Protein C, 32, 43, 189, 190, 223, 238, 251 Protein Kinases, 54, 238 Protein S, 52, 196, 204, 217, 238, 243, 247 Proteinuria, 22, 49, 228, 236, 238 Proteolytic, 190, 202, 238 Protocol, 28, 37, 238 Protons, 46, 190, 217, 238, 239 Protozoa, 203, 226, 239 Proximal, 8, 19, 46, 48, 56, 62, 103, 207, 239
Pseudohypoaldosteronism, 44, 58, 88, 91, 93, 110, 239 Psychiatric, 56, 239 Psychiatry, 31, 239 Psychic, 225, 239 Psychoactive, 239, 253 Public Health, 153, 170, 239 Public Policy, 169, 239 Publishing, 66, 162, 239 Pulmonary, 36, 196, 204, 221, 222, 239, 245, 252 Pulmonary Artery, 196, 239, 252 Pulmonary Edema, 221, 239 Pulse, 226, 239 Q Quality of Life, 19, 239, 250 Quiescent, 8, 239 R Race, 96, 226, 239 Radiation, 162, 191, 194, 209, 212, 218, 239, 243, 253 Radioactive, 66, 194, 196, 217, 223, 229, 239, 243 Radioimmunoassay, 59, 80, 88, 127, 239 Ramipril, 38, 240 Random Allocation, 240 Randomization, 6, 47, 240 Randomized, 5, 20, 22, 37, 50, 208, 240 Randomized clinical trial, 5, 23, 240 Rauwolfia, 136, 240, 241 Reabsorption, 8, 18, 19, 24, 37, 56, 58, 142, 149, 162, 240 Reactive Oxygen Species, 9, 15, 240 Recombinant, 22, 62, 78, 240, 252 Recombination, 92, 203, 213, 240 Rectum, 193, 201, 206, 213, 219, 222, 238, 240 Recurrence, 200, 240 Red blood cells, 210, 231, 240, 243 Reductase, 21, 149, 240 Refer, 1, 201, 223, 224, 229, 241, 250 Reflex, 15, 33, 241 Refraction, 241, 246 Refractory, 7, 158, 241 Regimen, 6, 37, 208, 241 Relaxant, 212, 241 Renal Artery, 58, 241 Renal Circulation, 158, 241 Renal cysts, 6, 241 Renal failure, 4, 49, 158, 161, 216, 241 Renal pelvis, 221, 241 Renal Plasma Flow, 49, 241
266
Aldosterone
Renal tubular, 5, 69, 158, 241 Renal tubular acidosis, 158, 241 Renin-Angiotensin System, 13, 14, 17, 24, 33, 38, 46, 77, 103, 114, 191, 198, 241 Renovascular, 33, 102, 241 Repressor, 39, 230, 241 Research Design, 11, 241 Research Support, 11, 241 Reserpine, 156, 240, 241 Resorption, 144, 149, 230, 240, 242 Respiration, 193, 226, 242 Respiratory failure, 211, 242 Response Elements, 43, 44, 242 Retina, 154, 200, 202, 206, 222, 224, 230, 242, 243, 253 Retinal, 154, 206, 230, 242 Retinal Ganglion Cells, 230, 242 Retinol, 242 Retroperitoneal, 188, 242 Retroviral vector, 17, 213, 242 Rhamnose, 230, 242 Rheumatoid, 231, 242 Rhinorrhea, 237, 242 Rhodopsin, 230, 242 Ribonucleic acid, 119, 129, 242, 243 Ribonucleoproteins, 229, 243 Ribose, 187, 243 Ribosome, 243, 250 Risk factor, 4, 9, 15, 16, 33, 34, 35, 60, 100, 210, 243 Risk patient, 9, 243 Rod, 195, 201, 243 S Saline, 20, 67, 243 Saliva, 243 Salivary, 88, 149, 243, 247 Saponins, 243, 246 Sarcosine, 13, 243 Scans, 6, 243 Schizoid, 243, 253 Schizophrenia, 243, 253 Schizotypal Personality Disorder, 243, 253 Sclerosis, 4, 243 Screening, 47, 82, 95, 112, 116, 144, 201, 243 Scrotum, 243, 251 Secretory, 8, 64, 218, 244 Segregation, 240, 244 Selective estrogen receptor modulator, 18, 244 Seminal vesicles, 244, 251 Seminiferous tubule, 244, 246
Semisynthetic, 196, 244 Sensor, 8, 244 Sepsis, 225, 244 Sequencing, 235, 244 Serotonin, 193, 229, 242, 244, 250 Serous, 194, 209, 244 Serum Albumin, 240, 244 Sex Characteristics, 188, 191, 244, 248 Shock, 218, 244, 250 Side effect, 17, 143, 148, 188, 193, 195, 198, 244, 250 Signal Transduction, 43, 61, 62, 220, 244 Signs and Symptoms, 145, 152, 161, 245 Skeletal, 32, 58, 149, 191, 201, 245 Skeleton, 187, 237, 245 Skull, 245, 248 Sleep apnea, 75, 107, 111, 245 Small intestine, 217, 220, 245 Smoke Inhalation Injury, 211, 245 Smooth muscle, 13, 47, 48, 64, 117, 134, 160, 194, 197, 212, 238, 241, 245, 247 Social Environment, 239, 245 Sodium Channels, 45, 52, 56, 58, 73, 245 Soft tissue, 196, 245 Solitary Nucleus, 194, 245 Somatic, 188, 217, 226, 232, 245, 251 Somatotropin, 218, 245 Specialist, 175, 207, 246 Species, 6, 12, 191, 210, 217, 226, 239, 240, 246, 247, 250, 252, 253 Specificity, 29, 41, 189, 246 Spectrum, 40, 246 Sperm, 8, 191, 200, 244, 246 Sperm Maturation, 8, 246 Spermatozoa, 8, 246, 251 Spinal cord, 196, 199, 200, 225, 228, 232, 241, 246, 248 Splanchnic Circulation, 158, 246 Splenic Vein, 235, 246 Sporadic, 228, 246 Stabilizer, 65, 198, 246 Staging, 243, 246 Steady state, 52, 246 Steel, 201, 246 Stem Cells, 210, 246 Sterile, 231, 246 Stimulant, 197, 221, 246 Stimulus, 143, 203, 208, 222, 241, 247, 249 Stomach, 187, 198, 206, 213, 214, 217, 227, 232, 245, 246, 247 Stool, 201, 219, 222, 247 Strand, 235, 247
267
Streptomycin, 204, 247 Stress, 12, 24, 33, 48, 56, 65, 183, 194, 199, 204, 227, 231, 236, 247, 250 Stroke, 27, 31, 60, 122, 145, 153, 168, 198, 247 Stroke Volume, 198, 247 Stroma, 232, 247 Subacute, 219, 247 Subcapsular, 247, 253 Subclinical, 219, 247 Subcutaneous, 40, 188, 208, 247 Subfornical Organ, 45, 247 Submandibular, 51, 247 Submaxillary, 210, 247 Subspecies, 246, 247 Substance P, 225, 236, 244, 247 Substrate, 54, 199, 210, 247 Suction, 212, 247 Superoxide, 12, 38, 48, 64, 247 Superoxide Dismutase, 38, 64, 247 Supplementation, 47, 55, 129, 130, 133, 248 Suppression, 14, 35, 38, 40, 63, 70, 76, 88, 94, 122, 160, 248 Suprarenal, 33, 248 Suspensions, 40, 248 Sweat, 123, 149, 151, 206, 248 Sweat Glands, 149, 151, 206, 248 Sympathectomy, 15, 248 Sympathetic Nervous System, 14, 24, 38, 45, 158, 191, 194, 248 Sympathomimetic, 207, 210, 229, 248 Symptomatic, 145, 152, 248 Synapse, 188, 248, 250 Synaptic, 229, 245, 248 Synergistic, 31, 37, 237, 248 Systemic, 14, 15, 30, 45, 49, 55, 59, 158, 193, 196, 210, 216, 219, 248, 251 Systolic, 6, 9, 86, 113, 217, 248 Systolic heart failure, 6, 248 T Temporal, 32, 33, 45, 90, 224, 248 Testicular, 160, 248 Testis, 211, 248 Testosterone, 8, 57, 240, 248 Tetany, 231, 249 Therapeutics, 104, 131, 220, 249 Thermal, 207, 229, 235, 249 Threshold, 217, 249 Thrombin, 212, 234, 238, 249 Thrombomodulin, 238, 249 Thrombosis, 27, 31, 238, 247, 249 Thromboxanes, 193, 249
Thyroid, 72, 160, 162, 197, 215, 227, 231, 232, 249, 251 Thyroid Gland, 162, 215, 227, 231, 232, 249 Thyroid Hormones, 249, 251 Thyroxine, 189, 233, 249 Tolerance, 139, 187, 214, 249 Tone, 45, 47, 61, 123, 229, 249 Tonicity, 221, 249 Tonus, 249 Tooth Preparation, 187, 249 Toxaemia, 236, 249 Toxic, iv, 161, 203, 206, 218, 229, 245, 250 Toxicity, 56, 132, 198, 250 Toxicology, 46, 56, 109, 170, 250 Toxin, 249, 250 Trachea, 197, 249, 250 Traction, 201, 250 Transcendental meditation, 134, 250 Transcription Factors, 21, 26, 43, 57, 242, 250 Transduction, 160, 244, 250 Transfection, 10, 43, 196, 213, 250 Translation, 10, 250 Translational, 28, 31, 250 Translocation, 48, 62, 250 Transmitter, 187, 207, 224, 229, 250 Transplantation, 4, 19, 29, 106, 118, 200, 224, 250 Trauma, 215, 228, 250 Trees, 240, 250 Triglyceride, 14, 217, 250 Trophic, 15, 250 Tryptophan, 201, 244, 250 Tumor marker, 195, 250 Type 2 diabetes, 40, 251 Tyrosine, 45, 48, 62, 127, 132, 134, 136, 207, 251 U Ubiquitin, 52, 251 Urea, 40, 56, 162, 221, 248, 251 Uremia, 158, 221, 241, 251 Ureters, 221, 241, 251 Urethra, 238, 251 Uric, 84, 162, 251 Urinary, 6, 24, 44, 46, 56, 60, 70, 83, 92, 108, 116, 144, 159, 219, 230, 235, 239, 251 Urinate, 251, 253 Urobilinogen, 162, 251 Uterus, 204, 225, 236, 251 V Vaccine, 238, 251 Vacuoles, 209, 251
268
Aldosterone
Vagal, 73, 251 Vagus Nerve, 245, 251 Vas Deferens, 8, 251 Vascular, 11, 12, 13, 15, 21, 26, 27, 30, 31, 32, 33, 45, 47, 50, 57, 61, 62, 64, 97, 104, 111, 117, 128, 134, 153, 160, 195, 197, 200, 205, 209, 219, 223, 226, 229, 234, 236, 249, 251 Vascular Resistance, 21, 195, 251 Vasculitis, 148, 252 Vasoactive, 30, 252 Vasoconstriction, 110, 210, 252 Vasodilation, 158, 191, 252 Vasodilator, 32, 50, 59, 65, 192, 196, 207, 217, 252 Vasomotor, 64, 252 Vector, 250, 252 Vein, 55, 191, 194, 220, 229, 235, 246, 252 Venous, 100, 109, 145, 152, 194, 205, 238, 252 Venous Pressure, 145, 152, 252 Ventricle, 203, 218, 239, 248, 252 Ventricular Dysfunction, 87, 113, 252 Ventricular Remodeling, 11, 84, 139, 252 Venules, 196, 197, 209, 226, 252 Veterinary Medicine, 169, 252 Viral, 17, 250, 252 Viral vector, 17, 252
Virulence, 194, 250, 252 Virus, 210, 213, 234, 242, 250, 252 Viscera, 225, 245, 246, 252, 253 Visceral, 4, 118, 194, 232, 251, 252, 253 Visceral Afferents, 194, 251, 253 Vitamin A, 220, 242, 253 Vitreous, 206, 222, 242, 253 Vitreous Body, 242, 253 Vitro, 10, 216, 253 Vivo, 26, 44, 46, 47, 57, 61, 253 Void, 29, 253 Volition, 220, 253 W White blood cell, 192, 223, 224, 229, 234, 253 Windpipe, 249, 253 Withdrawal, 6, 58, 78, 253 Wound Healing, 21, 33, 224, 253 X Xenograft, 192, 253 X-ray, 202, 212, 229, 243, 246, 253 Y Yeasts, 233, 253 Z Zona Glomerulosa, 12, 68, 107, 122, 131, 136, 142, 253 Zygote, 202, 203, 253 Zymogen, 238, 253
