The year 2010 marks the centennial for the identification of histamine and the first glimpse of its many physiological functions. From these initial findings a rich tapestry of research has uncovered roles for histamine in almost every physiological process with new findings emerging every year. These diverse roles of histamine have made for fertile ground for the discovery of novel therapeutics, and these drugs have been so successful that the term "antihistamine" has entered the common lexicon. This volume is an attempt to give a snapshot in time as to the current understanding of the role of histamine in just one important therapeutic area-inflammation. The first three chapters provide some background context for the rest of the book starting out with a historical perspective by Figueroa and Shankley. Bongers et al provide an overview of the pharmacology of the four histamine receptors and the chapter by Hiroshi Ohtsu describes how histamine is synthesized as well as the insights derived from mice where this synthesis is disrupted. The next several chapters discuss disease areas where histamine is known to be involved. Chapter 4 by Thomas Taylor-Clark outlines the role of histamine in allergic rhinitis, an area were antihistamines are commonly used. This is also true for ocular allergy as discussed by Ohbayashi et al. Both of these chapters highlight aspects of these conditions that are still not well-controlled and suggest the utility of new antihistamines targeting other histamine receptors.

In 1979 Dr Sperelakis published the `Origin of the Cardiac Resting Potential' in the Handbook of Physiology of the Heart. Since that time, many investigators and teachers of membrane biophysics have used this article as a source of reference on the fundamental principles and equations describing the factors that establish the resting potential in excitable and non-excitable cells. Professor Sperelakis has expanded the scope of this article to provide the present book, creating a comprehensive work and an invaluable reference on the electrophysiological concepts underlying cellular excitability. There has long been a need for a text which precisely defines the assumptions underlying the derivations and equations that describe the principles of electrical excitability and maintenance of ion gradients in excitable cells. Here, Professor Sperelakis not only defines the equations and underlying concepts of membrane potentials, but gives working examples of solutions, thus allowing investigators to utilize the fundamental principles in their research, and students of membrane physiology to establish a sound basis of electrophysiological theory. `I have used the `Origin of the Cardiac Resting Potential' in graduate courses on cell physiology and biophysics, and look forward to using this new book. The time and effort required to put this work together reflects the dedication of Dr Sperelakis to the field of membrane biophysics and electrophysiology in his long, productive career.' From the Foreword by Dr David R. Harder.

Nitric Oxide in Transplant Rejection and Anti-Tumor Defense represents a unique combination of three interrelated topics that is unavailable in any other single work: The detection and visualization of nitric oxide in biological materials using EPR spectroscopy and EPR imaging; Nitric oxide in immune mechanisms of allograft rejection; and The involvement of nitric oxide in anti-tumor defense. By bringing together specialists from these three disciplines, the book investigates the common molecular and cellular mechanisms underlying phenomena in transplants and oncology. In addition, the book provides an introduction to biological applications of EPR spectroscopy and imaging. Nitric Oxide in Transplant Rejection and Anti-Tumor Defense will appeal to researchers and graduate-level students investigating transplant rejections and their immune mechanisms, anti-tumor immune defenses, novel types of contrast agents for EPR imaging, and biological applications of EPR spectroscopy and EPR imaging.

This book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism. Special attention will be paid to methods of oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. This book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

Conceptually unsavoury, airway mucus is vital to homeostasis in the respiratory tract. In contrast, when abnormal, mucus contributes significantly to the pathophysiology of a number of severe bronchial diseases, including asthma, chronic bronchitis and cystic fibrosis. This volume provides wide ranging and in-depth coverage of the scientific and clinical aspects of airway mucus. It commences with introductory chapters which address the biochemical and molecular biological basis of airway mucus and continues with comprehensive coverage of the various physiological and rheological aspects of respiratory secretions. The clinical aspects of the topic are then considered, with chapters discussing the involvement of mucus secretions in bacterial infection and in hypersecretory diseases of the airway. The volume concludes with a discussion of the therapeutic aspects of the topic, both in terms of the possible approaches to the treatment of mucus hypersecretion and the interaction of these drugs with airway mucus. Written by leading experts in the field, each contribution provides a comprehensive review of its particular subject. Reflecting the latest advances in this important area of respiratory research, this volume will be of great interest to scientists and clinicians working in the field of airway secretions and related areas.

Food or calorie restriction has been shown in many short-lived animals and the rhesus monkey to prolong life-span. Life-long nutrition studies are not possible in humans because of their long survival. Studies over two to six years in healthy adult humans have, however, shown that a 20% reduction in food or calorie intake slows many indices of normal and disease-related aging. Thus, it is widely believed that long-term reduction in calorie or food intake will delay the onset of age-related diseases such as heart disease, diabetes and cancer, and so prolong life.

Over the last 20 or more years there has been a progressive rise in food intake in many countries of the world, accompanied by a rising incidence of obesity. Thus our increasing food and calorie intake has been linked to the rising incidence of cardiovascular disease and diabetes in early adult life. It is accepted that overeating, accompanied by reduced physical exercise, will lead to more age-related diseases and shortening of life-span. The answer is to reduce our calorie intake, improve our diet, and exercise more. But calorie restriction is extremely difficult to maintain for long periods. How then can we solve this problem?

Edited by a team of highly distinguished academics, this book provides the latest information on the beneficial effects of calorie restriction on health and life-span. This book brings us closer to an understanding at the molecular, cellular and whole organism level of the way forward.

Proceedings of an international symposium, held in Ulm, Germany, September 21-24, 1994

This book brings together the various fields of functional genomics and systems biology that provide information on metabolic function. There is special emphasis on the identification of drug targets. The book includes practical examples from the various "omic" sciences as well as theoretical examples of how integrated knowledge of these sciences can be applied to drug discovery. It is of interest to researchers in the pharmaceutical drug discovery environment.

This conference and monograph were the result of many collective efforts. The whole concept was formulated one early Wednesday morning at our weekly research meeting at Children's Hospital in our division of urology. We have been most fortunate to have a close collaboration with Bob Levin, Ed Macarak, and Pam Howard who have helped steer the course of our division's growing interest in basic science. At our weekly meetings our laboratory fellow will summarize their current work. Other ongoing areas of investigation in our labs and elsewhere are discussed. We have always made an effort to try and understand what other groups are doing who are working in the area of bladder smooth muscle research. It occurred to us that the best way to really know what everyone working in this field was doing would be to sponsor a 2-day meeting where we could all gather to discuss our ongoing work. A major limitation of the annual meeting of the American Urologic Association or the urology section of the American Academy of Pediatrics is that the scientfic sessions are limited as these are meant to be primarily clinical meetings (as they should be). For this reason the idea of a meeting devoted solely to research about the urinary bladder had great appeal. In addition to allowing for longer presentations than the standard 5 to 7 minutes, every effort would be made to encourage a dialogue amongst the presenters and the audience.

Strong body odor is a condition for which, until now, there have been few treatment methods. The Japanese authors, encouraged by the willingness of Oriental patients to undergo radical treatment, have developed the subcutaneous tissue shaving method, which eliminates the condition in a very short period of time without ugly scarring. The book Human Body Odor not only introduces the completely new subcutaneous tissue shaving method, it also questions conventional theories on the hair cycle itself and throws a new hypothesis about the process of hair generation and regeneration into the scientific arena. This could even lead in the future to a formula for retarding hair loss! Developed over the past twenty years, the authors' new surgical method for the radical treatment of bromidrosis represents a landmark in cosmetic surgery and dermatology!

Nutrition and Osteoporosis: Seeing Through a Glass, Darkly (1 Cor. 13:12) This volume of Advances in Nutritional Research deals with the present state of knowledge relative to the role of nutrition in the etiology of osteoporosis, one of the most serious degenerative diseases in the aging population. As a back drop for subsequent chapters on specific nutrients, Chapter 1 provides a com prehensive account of the gain and loss of bone throughout the life cycle, with emphasis on the architectural changes in later life that predispose to osteoporotic bone fractures. Chapter 2 documents the occurrence of aging bone loss through out human archeological history and Chapter 3 extends this documentation to all non-human vertebrate species so far examined, including primates living in the wild. It is apparent that a progressive loss of bone tissue is a normal accompaniment of aging among higher vertebrates. Whether it is a cause of bone fractures in animals, as it is in humans, is still unknown. It has also been established that there are significant differences in the frequency of osteoporotic fractures among human families, ethnic groups, national populations and diet cultures. Numerous studies have been carried out in an effort to explain these differences, and many of these deal with the possible effect of nutrition. Protracted controversies over the role of nutrition in the etiology of osteoporosis are reflected in the contents of several of the ensuing chapters."

Discusses the elements of the human body. Includes suggestions for related experiments and projects.

Comprehensive overview of different aspects of autophagy as it relates to neurodegenerative diseases. The pathogenesis of the main neurodegenerative disorders includes either the accumulation of altered or misfolded proteins or exposure to several toxics. Autophagy constitute one of the two principal cellular pathways implicate in the clearance of these material and can serve as a neuroprotective mechanism. Topics include: the role of autophagy in the brain, the role of autophagy in the principal neurodegenerative disorders, and the mechanism by which different molecules cause neurotoxicity and the role autophagy plays.

The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney. A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are associated with these diseases. Mutations have been identified in the fluid phase alternative pathway regulator Factor H and the membrane regulator Membrane Cofactor Protein MCP (CD46). The functional characterization of the mutant proteins allows to define the pathophysiological events on a molecular level. These new concepts and data on disease mechanisms already allowed to establish new diagnostic and novel promising therapeutic approaches for several human kidney diseases.

This timely book provides an overview of topics related to obesity. These include associated health risks, childhood obesity, genetics, evaluation, treatment, behavioral strategies, and successes and failures in preventing obesity. The volume covers evaluation guidelines, different approaches to treatment, including diet, exercise, behavior, drugs, and surgery to deal with the current world-wide obesity epidemic.

Application of recent advances, such as non-equilibrium thermodynamics, the maintenance concept and the material balancing method, to the description, of microbial growth has suggested new experimental approaches which have yielded a wealth of data. These data have been used to develop mathematical models of microbial growth and metabolism, and the models have made it possible to direct the metabolism of a microorganism in such a way that more of a certain desired product is made. While a full quantitative description of all aspects of microbial growth and metabolism is till remote, the new approaches are opening up large areas of new potential -- it is now possible, for instance, to deal with individual cells in a population and with quantitative aspects of product formation and optimisation. Microbiologists, biochemists and physiologists will find this an invaluable update on a field of great promise.

Roger Cone and a distinguished team of expert investigators provide the first major treatment of this critically important receptor family. The book illuminates the structure and function of these receptors through a wide-ranging review of the latest findings concerning the biology, physiology, and pharmacology of their peptide ligands and covers the major melanocortin peptides, Melanocortin-1-Receptors through Melanocortin-5-Receptors. Topics include the characterization of the melanocortin receptors, the biochemical mechanism of receptor action, and receptor function and regulation. Timely and authoritative, The Melanocortin Receptors offers an up-to-date knowledge base on the remarkably complex structure and functions of the melanocortins, a guide that will prove invaluable for today's neuroscientists, endocrinologists, pharmacologists, and other clinical and experimental investigators working in this fast moving field.

This is the 3rd volume in a series of reviews centered on the single major topic of bone replacement, discussing the biology of stem cells and cell signals, the knowledge needed to make stem cell-engineered bone tissue a reality, and how to prevent bone allograft infection. Useful as a followup to its predecessors, and as a stand-alone reference, it will interest a broad audience from orthopedists and bioengineers to dentists.

Challenging and provocative overviews are presented in Volume 40 of Current Topics in Membranes. Topics on cell lipids vary from basic themes such as biosynthesis and membrane distribution to the role of lipids in intracellular signaling and membrane flow. This single volume also highlights the roles of lipids in eukaryotic cells and discusses organization of lipids in microdomains.

In 1962, 30 years after the discovery by du Vigneaud have pathologic consequences. One potentially sig- of a new sulfur amino acid, homocysteine; Carson and nificant health outcome of such mild to moderate Neil reported two siblings with mental retardation in hyperhomocysteinemia is an increased risk of occlu- northern Ireland with elevated urinary homocystine. sive vascular disease. Homocysteine concentrations in Nearly simultaneously, Gerritsen and Waisman patients with vascular disease were, on average, 31 % greater than in normal controls. Prospective assess- identified increased homocystine in the urine of a mentally retarded infant in Wisconsin. Within two ment of vascular disease risk among men with higher years, Harvey Mudd, James Finkelstein, and their homocysteine concentrations indicated that plasma coworkers at the National Institutes of health (USA) homocysteine at only 12% above the upper limit of that the enzyme cystathionine ~- normal levels was associated with a 3. 4-fold increase had reported synthase was lacking in a liver biopsy specimen from in risk of acute myocardial infarction. Studies from another patient with homocystinuria. This was the original Framingham Heart Study cohort (USA) the first indication of a vitamin relationship to have shown strong, positive correlation between homocystinuria, because that enzyme has as its co- plasma homocysteine concentration and degree of factor vitamin B6 (pyridoxal phosphate). Thereafter, carotid stenosis.

1 2 MARCEL B. ROBERFROID AND GLENN R. GIBSON 1 Universite Catholique de Louvain, Department of Pharmaceutical Sciences, Avenue Mounier 73, B-1200 Brussels, BELGIUM 2 Food Microbial Sciences Unit, Department of Food Science and Technology, The University of Reading, Reading, UK It is clear that diet fulfils a number of important human requirements. These include the provision of sufficient nutrients to meet the requirements of essential metabolic pathways, as well as the sensory (and social) values associated with eating. It is also evident that diet may control and modulate various body functions in a manner that can reduce the risk of certain diseases. This very broad view of nutrition has led to the development of foodstuffs with added "functionality." Many different definitions of functional foods have arisen. Most of these complicate the simple issue that a functional food is merely a dietary ingredient(s) that can have positive properties above its normal nutritional value. Other terms used to describe such foods include vitafoods, nutraceuticals, pharmafoods, foods for specified health use, health foods, designer foods, etc. Despite some trepidation, the concept has recently attracted much interest through a vast number of articles in both the popular and scientific media.

Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences. Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas. The sigma receptor was originally thought to be a subset of the opioid receptor family, and it is less than 10 years since it was recognized that this receptor represents unique binding sites in mammalian brain and peripheral organs, distinct from any other known neurotransmitter receptor. Since the sigma receptors exhibit high affinity for members of diverse classes of psychotropic drugs, and have been postulated to be involved in various central nervous disorders, neuroscientists have demonstrated a great deal of interest in the elucidation of these receptor sites and their biological relevance. Relatively little is known about the precise role of sigma receptors in normal brain function and in CNS disorders, despite an overwhelming research effort. This research has resulted in many controversies, some of which have been reconciled while others have not. This volume aims to update the reader on the current situation, and deals with the potential functional significance of these receptors in the brain and peripheral organs and, where appropriate, makes reference to the clinical potential of these sites.

In one generation, the numerous factors involved in blood coagulation have become real protein entities, isolated in pure form, expressed by recombinant DNA techniques, and subjected to structure elucidation by the modem methods of physical chemistry, viz. , X-ray diffraction, and NMR, ESR and fluorescence spectroscopy. The major milestone in this field was the breakthrough achieved by W. Bode, R. Huber and their colleagues in 1989 in of human a-thrombin, inhibited with D-Phe-Pro-Arg determining the crystal structure chioromethyl ketone. The availability of this structure will greatly facilitate the interpretation of experiments designed to gain an understanding of the interatomic interactions between this enzyme and fibrinogen and its other substrates. At the same time, it provides a rational basis for the design and synthesis of inhibitors of thrombin, the subject of this symposium. The symposium was organized in four sessions: (1) Structural features of the interaction of thrombin with substrates and inhibitors, (2) Synthetic inhibitors, (3) Hirudin and its analogues, and (4) Pharmacological and clinical considerations. This book contains summaries of most of the papers presented, and takes its rigbful place among two others that provide a comprehensive picture of our current knowledge about thrombin, viz. the 1977 volume entitled "Chemistry and Biology of Thrombin", edited by R. L. Lundblad, J. W. Fenton II, and K. G. Mann, and the 1992 volume entitled "Thrombin: Structure and Function", edited by L. J. Berliner.