More than 70 years have elapsed since U. S. von Euler and I. H. Gaddum dis- covered an unidentified depressor substance in the brain and gut. The effects of the powdery extracts were marked as 'P' on the kymograph tracings, and the nondescript name of 'substance P' still carries the breath of this adventurous period. In the 1960s, substance P returned in another disguise, staging as a hypothalamic peptide that causes copious salivary secretion (see chapter by F. Lembeck and I. Donnerer). This time, though, the mysterious substance was tracked down by S. E. Leeman and her collaborators as an undecapeptide, after it had eluded its identification for some 40 years. Substance P turned out to be the mammalian counterpart of a family of peptides which had been extracted from amphibian and nonvertebrate species and which had been given the name 'tachykinins' by V. Erspamer. Soon novel members of this peptide family were discovered, and in mammals substance P was joined by neurokinin A and neu- rokinin B. The presence of tachykinins in frog skin as well as in venoms and toxins of microbes and arachnids raises the possibility that these peptides re- present an old system of biological weapons that have been transformed to a particular messenger system in mammals.

This volume explores all aspects of vascular biochemistry and includes chapters that provide an understanding of vascular function with descriptions of tissue components present in the vascular wall as well as an exploration of the hemodynamic and metabolic activities associated with this function. In addition, some chapters explore the vasculature under conditions which mimic various disease states. The information provided in this volume will provide new insights into the mechanisms that control vascular function as well as therapies designed to treat vascular disease.

Hypoxia, defined as reduced oxygen tension, is a common physiological phenomenon in both normal embryonic development and malignancy progression. Although severe hypoxia is generally toxic for both normal tissue and tumors, neoplastic cells gradually adapt to prolonged hypoxia though additional genetic and genomic changes with a net result that hypoxia promotes tumor progression and therapeutic resistance. Hypoxia promotes cancer progression by regulating various aspects of cancer biology, including radiotherapy resistance, metabolism, angiogenesis and invasion/migration.

Diabetes is an autoimmune, inflammatory disease affecting many different organ systems and exhibiting both primary and secondary defects. Because diabetes affects a wide range of cellular systems, a multidisciplinary effort has been mounted over the past several decades using a wide range of investigative techniques and methodologies in order to identify molecular mechanisms responsible for cellular dysfunction. Because primary defects at various levels of sub-cellular signaling, intracellular calcium handling, protein expression and energy regulation are often a primary consequence of diabetes. This volume is a compilation of new multidisciplinary research that will broaden our current understanding of diabetes and cardiovascular disease as well as provide the basis for the development of novel therapeutic interventions.

This monograph evolved from years of research into the auditory pathway and hearing of many species of marsupials. Its function is to give biologists, in par ticular neurobiologists, a broad description and review of what is known of the auditory sensory capacities and processing mechanisms in this large order of mammals. My initial interest in marsupials developed from collaborative work with Dr. Richard Gates at Monash and Melbourne Universities in the 1970s and by curiosity as to whether concepts about the auditory system was stimulated stemming from experiments mainly on domestic cats could be extended to mam mals of other orders. My subsequent interest in Australian marsupials, aroused by collaboration with Dr. John Nelson at Monash University in the 1980s and 1990s, concerned their auditory systems and behavior per se and not as primitive cousins of eutherians. More recently, I have collaborated with Dr. Bruce Masterton at Florida State University in studies of New World marsupials. His sad death in 1996 has robbed neurobiologists of one of our most provocative thinkers and hypothesis testers. I would like to thank the Department of Physiology at Monash University for making many facilities available to me, the National Health and Medical Research of Australia and the Australian Research Council for providing funds for Council research, and Jill Poynton and Michelle Mulholland, who illustrated this volume."

Chronic obstructive pulmonary disease (COPD) ranges amongst the commonest diseases in the world. The relentless progression of the disease causes a pressing need for a better understanding of and therapies for COPD. This volume provides state-of-the-art information on the pathophysiology of COPD including an outlook on new therapies. It is of interest to researchers and clinicians in academia as well as in the pharmaceutical industry.

Parameters such as membrane transport, metabolism and protein incorporation govern the fate of amino acids in living tissue. Is it possible to use positron tomography to measure some of them, and what is their meaning in normal and pathological situations? These questions have been addressed for a long time and no satisfactory answer has yet been given. This book, which derives from an EEC workshop organized in the frame of the Concerted Action on PET Investigation of Cellular Regeneration and Degeneration', held in Lyon in February 1992, gives the present state of knowledge in this field based on the most recent studies. Contributions from 24 leading European and American scientists are presented and discussed in the following four parts: biochemistry and animal studies; amino acids labelling with positron emittors, quality control and metabolites measurement; kinetic modelling of amino acids transport, metabolism, and protein incorporation; clinical use of amino acids. This book will aid and interest biochemists, radiochemists, pharmacologists, neurologists, oncologists and medical imaging scientists.

This, the 148th volume of the Handbook of Experimental Pharmacology series, focuses on the very core of pharmacology, namely receptor theory. It is fitting that the originator of receptor pharmacology, A. J. CLARK, authored the fourth volume of this series 63 years ago. In that volume CLARK further developed his version of receptor theory first described four years earlier in his classic book The Mode of Action of Drugs. An examination of the topics covered in volume 4 reveals a striking similarity to the topics covered in this present volume; pharmacologists today are still as interested in unlocking the secrets of dose-response relationships to reveal the biological and che mical basis of drug action as they were over half a century ago. Sections in that 1937 volume such as "Curves relating exposure to drugs with biological effects" and "Implications of monomolecular theory" show Clark's keen insight into the essential questions that required answers to move pharma cology forward. With the advent of molecular biological cloning of human receptors has come a transformation of receptor pharmacology. Thus the expression of human receptors into surrogate host cells helped unlock secrets of receptor mechanisms and stimulus-transduction pathways. To a large extent, this elim inates the leap of faith required to apply receptor activity of drugs tested on animal receptor systems to the human therapeutic arena. However, a new leap of faith concerning the veracity of the effects found in recombinant systems with respect to natural ones is now required.

This drug is a landmark discovery, which consequently has become the definitive therapy for the treatment of erectile dysfunction (ED). Following the major breakthrough in the field of nitric oxide (NO)-physiology and pharmacology leading to sildenafil being marketed, the most current information is presented in this reference book, including ongoing research from several disparate groups about NO as endothelium-derived relaxing factor (EDRF) and also as a neurotransmitter for nerves innervating erectile tissue in mammals.

The development of sildenafil as an oral phosphodiesterase-5 (PDE5) inhibitor drug for the treatment of ED resulted in one of the first products, which made its way successfully from basic NO research to routine clinical therapy.

This volume addresses all fields of sildenafil application in both men and women. In a highly competitive research environment with a critical medical need for drug improvements the reader will learn more about clinical resistance to sildenafil treatment and the modalities to overcome the failure rates.

The individual chapters cover clinical use, pharmacokinetics, pharmacodynamics, biochemistry, and cultural aspects. They are written by leading experts in their respective fields. Therefore, readers whether professionals in the pharmaceutical industry, physicians treating ED, biochemists, chemists or pharmacologists will find a detailed and up-to-date knowledge base about current research activities and an excellent overview for further research on this compound class and its cultural impact."

The study and modulation of cortical connections is a rapidly growing area in neuroscience. This unique book by prominent researchers in the field covers recent advances in this area. The first section of the book describes studies of cortical connections, modulation of cortical connectivity and changes in cortical connections with activities such as motor learning and grasping in primates. The second section covers the use of non-invasive brain stimulation to study and modulate cortical connectivity in humans. The last section describes changes in brain connectivity in neurological and psychiatric diseases, and potential new treatments that manipulate brain connectivity. This book provides an up-to-date view of the study of cortical connectivity, and covers its role in both fundamental neuroscience and potential clinical applications.

Electric currents and electromagnetic fields have been applied to biological systems, particularly humans, with both therapeutic and pathological results. This text discusses biological responses to electric currents and electromagnetic fields, including medical applications and shock hazards. It covers fundamental physical and engineering principles of responses to short-term electrical exposure and emphasises human reactions, although animal responses are considered as well, and the treatment covers reactions from the just-detectable to the clearly detrimental. An important new chapter discusses standards for human exposure to electromagnetic fields and electric current and demonstrates how these standards have been developed using the principles treated in earlier chapters.

Ghrelin, the endogenous ligand for the growth hormone secretagogue (GHS) receptor, is critical in the control of food intake and energy balance. The ghrelin receptors are now known to have important physiological properties as modulators of growth hormone release, appetite, glucose homeostasis, metabolism, immune function, neurotransmitter activity, cognitive function and neurodegeneration. Bringing all of this information together in the first comprehensive text on the topic, Ghrelin in Health and Disease provides a state-of-the-art synthesis of the latest work in this area for physicians and physician-scientists. This volume addresses the unique property of ghrelin as a modulator of function. Such a property provides potential utility for safe intervention in a wide variety of disease states. Indeed as we learn more about the basic physiology of ghrelin, the potential for treating new disease targets emerge requiring validation in the clinic. Each chapter in this volume is authored by a leading investigator in the field. The introductory chapter sets the background for the book and provides a superb overview of the relevance of ghrelin to physiology, describing how the discovery of ghrelin has prompted us to completely rethink traditional physiology. The authors conclude their chapters by critically addressing the future translational aspects of ghrelin biology and outlining what key basic research and clinical questions remain to be addressed. An invaluable resource, Ghrelin in Health and Disease distinguishes itself as the first comprehensive title covering all of the molecular and clinical issues relating to ghrelin and advancing our clinical understanding of obesity, growth, and reproductive pathogenesis.

Arterial chemoreceptors are unique structures which continuously monitor changes in arterial blood oxygen, carbon dioxide, glucose, and acid. Alterations in these gases are almost instantaneously sensed by arterial chemoreceptors and relayed into a physiological response which restores blood homeostasis. Arterial Chemoreception contains updated material regarding the physiology of the primary arterial chemoreceptor; the carotid body. Moreover, this book also explores tantalizing evidence regarding the contribution of the aortic bodies, chromaffin cells, lung neuroepithelial bodies, and brainstem areas involved in monitoring changes in blood gases. Furthermore this collection includes data showing the critical importance of these chemoreceptors in the pathophysiology of human disease and possible therapeutic treatments. This book is a required text for any researcher in the field of arterial chemoreception for years to come. It is also a critical text for physicians searching for bench-to-bedside treatments for heart failure, sleep apnea, and pulmonary hypertension.

Skeletal muscle consumes significant amounts of oxygen, and its oxygen flux increases significantly under conditions of exercise and muscle contraction. This makes the muscle vulnerable to oxidative stress since concomitantly with the increase of oxygen flow there is an increase of free oxygen radicals which are a byproduct of muscle respiration. A number of studies in the last decade have documented the involvement of free oxygen radicals in exercising muscles. The consequences of muscle oxidative stress have resulted mainly in increased muscle protein oxidation, elevation of lipid peroxidation, and depletion of muscle antioxidants. The mechanisms of this oxidative stress are under extensive investigation in laboratories around the world and are topics of the chapters in this volume. This book is intended for professionals who are interested in muscle function, physiology, pathophysiology and well-being, such as therapists, trainers and medical professionals as well as for researchers in the field of muscle physiology.

"Nitric Oxide and Free Radicals in Peripheral Neurotransmission" is a welcome addition to the literature and describes current research into the role of nitric oxide in the peripheral nervous system and its associated organs. Topics covered range from general consideration of nitrergic transmission, in its broadest sense, to elaboration of our current understanding of the role of nitric oxide in transmission in individual peripheral organs, including its role as a backup, or alternate as well as chief transmitter. The influence of nitric oxide and related compounds on the more conventional modes of autonomic transmission are also considered. Aimed at students and researchers in the areas of neuroscience and physiology, "Nitric Oxide and Free Radicals in Peripheral Neurotransmission" also covers the emerging role of abnormal nitric oxide function in disease states and, where appropriate, as potential avenues of therapy.

Proceedings of an International Workshop held in Sheffield, UK, September 1-4, 1997

Gasps, sighs, and yawns are recognized by even a casual observer as involuntary expressions of emotion through the "medium" of respiration. In recent years, scientific observation has focused on sensation and behavior as researchers investigate the relation of emotion and stress in disorders such as asthma, hyperventilation, and panic disorder. Until now, however, the interplay of psychological factors and physiological responses has not been approached from the interdisciplinary perspective reported in this book. Brought together here is the work of physiologists, psychologists, and researchers in behavioral medicine, together with - for the first time - specialists and practitioners of traditional Japanese arts and culture. Knowledge of the art and control of breathing, which are essential features of such disciplines as Zen and Noh, opens a new and until now unexplored path for scientists seeking to understand the relation between respiration and emotion.

Recent research suggests that adult growth hormone (GH) deficiency, whether of pathological or physiological origin, is associated with a dis tinct syndrome that includes alterations in body composition, endocrine metabolic function, immune competence, and physical and psychosocial well-being. Not surprisingly, substantial investigative effort is currently focused on validating the above hypothesis and on determining whether restoration of a normal GH-IGF-I axis in various states of adult GH deficiency is clinically useful, safe, and cost-beneficial. This book contains the proceedings from the Symposium on GHRH, GH, and IGF-I: Basic and Clinical Advances, held December 9 to 12, 1993, in San Diego, California, and sponsored by Serono Symposia USA, Inc. The conference was meant to highlight selected novel and exciting clinical research developments related to possible therapeutic uses of recombinant human GH and IGF-I, GHRH, GH releasing peptides, and related GH secretagogues. This meeting occurred only one year after a similar Serono symposium that was somewhat more oriented to novel basic science discoveries, thus attesting to the current scientific and clinical interest in this area.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. "Cardiac Adaptations" will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities."

The Taurine Symposium- "Taurine: Beginning the 21'' Century"- was held September 20-23, 2002, on the beautiful island of Kauai in Hawaii. The headquarters of the meeting was the Radisson Kauai Beach Resort. This international meeting was attending by approximately 80 individuals from 23 nations and 4 continents. Seventy-five papers were presented either as platform presentations or poster presentations. Taurine, first isolated from ox bile in 1827 by Tiedemann and Gmelin and named in 1838 by Demarcay, became of significant scientific interest in 1968 when the first extensive review article was published by Jacobsen and Smith. Interest in taurine grew exponentially after 1975 when the first taurine symposium was organized by Ryan Huxtable in Tucson, Arizona. Since that date, taurine symposia have been held approximately every two years held in various cities and resort areas around the world. Taurine investigators have had the privilege of attending these scientific meetings on three continents - Asia, Europe, and North America. Since the initial meeting in 1975, a central question addressed during many of the symposia has been: "What is physiological, pharmacological, nutritional, and pathological role of taurine?". Although taurine has been established as an important osmolyte, it appears to affect many other biological processes. However, the exact mechanism(s) by "which taurine acts" has not yet been definitively answered. In Kauai, the patticipants discussed many topics and asked many questions regarding the role and actions of taurine.

Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.

This monograph covers the entire field of blood group serology, with its main emphasis on the chemical and biochemical basis of blood group specificity. Full consideration is given to molecular biology investigations, in particular to studies on the structure of blood group genes and the molecular biological basis of alleles and rare blood group variants, whereby relevant literature up to the year 2000 is covered. The text is supplemented by numerous illustrations and tables, and detailed reference lists.

th This volume contains selected lectures presented at the 12 International Conference on Advances in Prostaglandin, Leukotriene and Other Bioactive Lipid Research: Basic Science and Clinical Applications which was held in Istanbul, Turkey, on August 25-29, 2002. This meeting brought together basic and clinical scientists for the purpose of discussing advances in bioactive lipid research with.special attention to cancer, cardiovascular diseases, gastrointestinal diseases and respiratory diseases. Topics covered included: the role of leukotrienes and lipoxins in of inflammation, the cytochrome P450 pathway, the genetics and genomics bioactive lipids, lipid peroxidation, apoptosis, angiogenesis, isoprostanes, receptors and inhibitors, cyclooxygenase and lipoxygenase pathways and inhibitors, prostaglandin synthases and receptor signaling, phospholipases and inhibitors. Sessions included plenary lectures with expertise in particular areas, oral presentation on selected topics and general poster sessions. J.M. Drazen (Boston, USA) discussed anti-leukotriene treatment in asthma patients while C. Brink (paris, France) presented the recent advances in leukotriene receptors. The recent advances in cytochrome p450 pathway described in the session organized by J.C. McGiff (Valhalla, NY, USA). T. Shimizu (Tokyo, Japan) and M. Balazy (Valhalla, NY, USA) gave an update on phospholipases and arachidonic acid peroxydation. The editors are greatful to the Organizing, Programme and Advisory Committees for their valuable contributions. We greatfully acknowledge the generous financial support provided by PharmaciaIPfizer, Fako Pharmaceuticals Inc. and Novartis Pharmaceuticals Inc. ofthe contributors to this volume, in particular We are also greatful to all to those who delivered their manuscripts by or before the requested deadline.

The field of neural control of breathing has advanced rapidly in the past two decades, with the emergence of many new and promising research directions of increasing sophistication. The complexity and diversity of the current methodologies signify its remarkable vivacity, albeit at the price of much confusion. Captured in this book are the broad and intricate nature of the field and its multifaceted frontiers, including aspects of genetics, cell and molecular biology, comparative biology, neurophysiology, neurochemistry, neuroanatomy, imaging, human physiology in health and disease, and influence of environmental factors. Major topics include chemosensitivity, respiratory sensation, respiratory neurons, rhythmogenesis, plasticity, development, chemoreflex and exercise, respiratory instability and variability with behavioral and sleep states, etc., which are systematically laid out in the book for easy referencing.