It is an exciting task to be the editor of the first monograph covering a new area of the biomedical sciences. Since the first report in 1980 by Robert Furchgott and colleagues (see Chapter 1) of the evidence of endothelium-dependent relaxation in isolated arteries, there are ever increasing numbers of vascular physiologists and pharmacologists who are scraping away the endothelium to look into its role in cardiovascular con trol. And the more one looks, the more one discovers. Not only is the list of substances that can induce endothelium-dependent relaxations im pressively long, but these intriguing cells can also secrete vasoconstrictor substances. The ability of the endothelium to modulate the degree of con traction of the underlying smooth muscle is an ancestral property of the blood vessel wall, illustrating the logic of nature, since the endothelial cells are located in the best possible strategic location to continuously monitor the properties (chemical or physical) of the blood. And more and more data emerge suggesting that in several cardiovascular diseases per turbations in endothelium-dependent responses are one of the early signs of the abnormal process. Thus, the importance of endothelium-dependent responses, triggered by the intellectual curiosity of one of the pioneers of vascular physiology and pharmacology, is now recognized not only by basic scientists, but also by all concerned with the cardiovascular diseases. The purpose of this monograph is to provide them with a reference work, so that they know where to start."

This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.

First published in 1986. Routledge is an imprint of Taylor & Francis, an informa company.

This book is concernced with the process of cell death in human cells by programmed cell death or apoptosis, and the modulation of this process by drugs. This is a new field of study and this volume represents the first comprehensive treatment of this subject matter. Its focus is on human biology and medicine. Apoptosis is a very prevalent type of cell death with importance in human diseases such as cancer, Alzheimer's disease and autoimmune disorders. The book combines the expertise of leading scientists and writers from fields as diverse as neurosciences, immunology, pathology and cancer research. There is detailed analysis of the molecular and cellular aspects of apoptosis including the specific genes and molecules involved in the regulation of this special form of programmed cell death. Scientists, clinicians and researchers involved in studies of human biology and medicine will find this book an excellent resource.

Fatigue is a condition spanning the breadth of human functioning in health and disease and is a central concern in sport and exercise. Even so we are yet to fully understand its causes. One reason for this lack of understanding is that we seldom consider fatigue from an evolutionary perspective - as an adaptation that provided reproductive success. This ground-breaking book outlines the evidence that fatigue is a result of adaptations distinctive to humans. It argues that humans developed adaptations which led to enhanced fatigue resistance compared with other mammals and discusses the implications in the context of exercise, health and performance. Highly illustrated throughout, it covers topics such as defining and measuring fatigue, the emotional aspect of fatigue, how thermoregulation affects the human capacity to resist fatigue, and fatigue in disease. Human Fatigue is essential reading for all exercise scientists as well as graduate and undergraduate students in the broad field of physiology and exercise physiology.

The 14th volume in the series will focus on cutting edge research at the interface of hypoxia and exercise. The work will cover the range from molecular mechanisms of muscle fatigue and muscle wasting to whole body exercise on the world 's highest mountains. State of the art papers on training at high altitude for low altitude athletic performance will also be featured.

Nearly everything making up what we call the "environment" of a plant has an infuence on the way it grows. Sunlight, te- perature, moisture contents of soil and atmosphere and vib- tions are all obvious examples of environmental components, and transient variations in their amount or intensity lead the plant to manifest more or less immediate responses. Small changes in carbon dioxide level in the atmosphere can even have effects, but these take a longer time to be registered - at least those that are visible, albeit at the microscopic level. Plants meet the challenges of the environment by means of acclimation. In this respect, plants are notable for the pl- ticity of their development. However, where morphological or physiological plasticity is no longer an option, the responses would be by means of adaptations as a result of genetic - lection or genetic "assimilation" (Waddington 1957). Thus, a feature that was once a facultative transient response to an environmental perturbation becomes a constitutive charac- ristic of plant structure or function. It is in this way that the environment continually molds the way in which plants de- lop, and also defnes the areas upon planet Earth where they will thrive.

First published in 1985. Routledge is an imprint of Taylor & Francis, an informa company.

This contributed volume presents the current state of research on regenerative rehabilitation across a broad range of neuro- and musculoskeletal tissues. At its core, the primary goal of regenerative rehabilitation is to restore function after damage to bones, skeletal muscles, cartilage, ligaments/tendons, or tissues of the central and peripheral nervous systems. The authors describe the physiology of these neuro- and musculoskeletal tissue types and their inherent plasticity. The latter quality is what enables these tissues to adapt to mechanical and/or chemical cues to improve functional capacity. As a result, readers will learn how regenerative rehabilitation exploits that quality, to trigger positive changes in tissue function. Combining basic, translational, and clinical aspects of the topic, the book offers a valuable resource for both scientists and clinicians in the regenerative rehabilitation field.

The prefrontal cortex is known to play important roles for performing a variety of higher cognitive functions. Among regions of the prefrontal cortex, the dorsolateral prefrontal cortex plays the most important roles for these functions. This book focuses on functions of the dorsolateral prefrontal cortex, summarizes research results obtained mainly by non-human primate studies, and describes neural mechanisms of executive functions that the dorsolateral prefrontal cortex participates. First, to understand the feature of the dorsolateral prefrontal cortex and how its function has been understood, anatomical and functional features of the dorsolateral prefrontal cortex and historical overview of prefrontal functions are described. To understand functions of the prefrontal cortex and neural mechanisms of executive functions, working memory is an important concept and sustained activation during the memory period of working memory tasks is known as a neural mechanism of working memory. Therefore, this book describes features of sustained memory-related activity based on neurophysiological results obtained in the prefrontal cortex and how memory-related activity contributes to executive functions including control of attention, inhibitory control, task management, and planning. And further, this book describes how the dorsolateral prefrontal cortex contributes to neural mechanisms for sensory and motor processing, memory control in multi-task performance, decision-making, metacognition, and top-down control. Thus, this book provides important information regarding neural mechanisms of dorsolateral prefrontal functions to neuroscientists and helps to plan further investigation to understand prefrontal functions in primates and human subjects.

First published in 1984. Routledge is an imprint of Taylor & Francis, an informa company.

This book is an edited collection of the literature on leptin beginning with the discovery of leptin and a study of its affect on animals and in humans. Chapters will focus on the discovery, history, roles and regulation of leptin in all the major areas of physiology, as well as on assay methods, phylogeny and genetics. The timing of this volume is long overdue and is the first comprehensive coverage of leptin physiology in the field.

This book covers the tremendous progress in the current understanding of the molecular physiology of voltage-gated calcium channels. This book includes unparalleled insights into structural features of calcium channels due to X-ray crystallography and cryo-EM, which in turn yielded critical information into how these channels function under normal and pathophysiological conditions, and how they interact with calcium channel therapeutics. The chapters investigate how, with the advent of high throughput genome sequencing, numerous mutations in various calcium channel genes have been identified in patients with neurological, cardiovascular, neuropsychiatric and other disorders. This is further complemented through a much larger in vivo toolkit such as knock-out and knock-in mice. The chapters further discuss the increased complexity of calcium channel physiology that arises from mRNA editing and splicing. Finally, the book also provides an overview of the updated research on calcium channel inhibitors that can be used both in vivo and in vitro, and which may serve as a spring board for new calcium channel therapeutics for human disease. Voltage-Gated Calcium Channels is useful for academic researchers at all levels in neuroscience, biophysics, cell biology and drug discovery.

The importance of polyamines for all living cells has been recognized since spermine was discovered in human semen more than 300 years ago. Polyamine research intensified when analytical methods were developed for their determination, particularly in tissues and biological fluids. Discovering their close correlation with cancer, and that polyamine concentrations change during the cell cycle, gave reason for further research in this topic. Polyamines in Health and Nutrition concentrates on the direction of polyamine research which has the capacity to influence and benefit our health and which can explain some of the discrepancies and failures of earlier research. It is important to recognize the dietary contribution to the polyamine body pool and to investigate how the polyamine content of the diet can be changed, with the ultimate aim of using this information to improve our health.

The overall scope of this new series will be to evolve an understanding of the genetic basis of (1) how early mesoderm commits to cells of a heart lineage that progressively and irreversibly assemble into a segmented, primary heart tube that can be remodeled into a four-chambered organ, and (2) how blood vessels are derived and assembled both in the heart and in the body. Our central aim is to establish a four-dimensional, spatiotemporal foundation for the heart and blood vessels that can be genetically dissected for function and mechanism. Since Robert DeHaan's seminal chapter "Morphogenesis of the Vertebrate Heart" pub lished in Organogenesis (Holt Reinhart & Winston, NY) in 1965, there have been surprisingly few books devoted to the subject of cardiovascular morphogenesis, despite the enormous growth of interest that occurred nationally and internationally. Most writings on the subject have been schol arly compilations of the proceedings of major national or international symposia or multiauthored volumes, often without a specific theme. What is missing are the unifying concepts that can make sense out of a burgeoning database of facts. The Editorial Board of this new series believes the time has come for a book series dedicated to cardiovascular morphogenesis that will serve not only as an important archival and didactic reference source for those who have recently come into the field but also as a guide to the evolution of a field that is clearly coming of age."

The Copenhagen Muscle Research Centre was founded in 1994 with the support of a grant from the Danish National Research Foundation. Among the goals for the Centre is the organization of research symposia, with the aim of bringing a limited number ofintemation ally renowned scientists together to discuss the latest developments and perspectives in their field. The first Copenhagen Muscle Research Centre Conference was held in 1995 and dealt with cardiovascular regulation. The Second Copenhagen Muscle Research Centre Confer ence was held from October 23-26, 1997. The topic of the Symposium was Muscle Metabo lism: Regulation, Exercise, and Diabetes. Seventy invited scientists from all over the world discussed their latest research related to skeletal muscle metabolism. The speakers were asked to expand on their presentations and to write short, but comprehensive, chapters about their given topics. The result is 28 peer-reviewed and edited chapters covering many if not all aspects of muscle energy metabolism related to exercise and diabetes. Emphasis is on regulation of glucose and fatty acid metabolism and the mechanisms regulating their use as fuels for the muscle during exercise. In addition, abnormalities in the regulation of glucose metabolism in the diabetic state are described. However, amino acid and protein metabolism are also thoroughly discussed. We believe that this volume brings an unparralleled, up to date, and comprehensive review of the frontiers in muscle metabolism. Erik A."

Nutrients have been recognized as essential for maximum growth, successful reproduction, and infection prevention since the 1940s; since that time, the lion's share of nutrient research has focused on defining their role in these processes. Around 1990, however, a major shift began in the way that researchers viewed some nutrients particularly the vitamins. This shift was motivated by the discovery that modest declines in vitamin nutritional status are associated with an increased risk of ill-health and disease (such as neural tube defects, heart disease, and cancer), especially in those populations or individuals who are genetically predisposed. In an effort to expand upon this new understanding of nutrient action, nutritionists are increasingly turning their focus to the mathematical modeling of nutrient kinetic data. The availability of suitably-tagged (isotope) nutrients (such as B-carotene, vitamin A, folate, among others), sensitive analytical methods to trace them in humans (mass spectrometry and accelerator mass spectrometry), and powerful software (capable of solving and manipulating differential equations efficiently and accurately), has allowed researchers to construct mathematical models aimed at characterizing the dynamic and kinetic behavior of key nutrients in vivo in humans at an unparalleled level of detail."

Upon completion of the human genome project over 800 G protein-coupled receptor 1 (GPCR) genes, subdivided into five categories, were identified. These receptors sense a diverse array of stimuli, including peptides, ions, lipid analogues, light and odour, in a discriminating fashion. Subsequently, they transduce a signal from the ligand-receptor complex into numerous cellular responses. The importance of GPCRs is further reflected in the fact that they constitute the most common target for therapeutic drugs across a 2 wide range of human disorders. Phylogenetic analysis of GPCRs produced the GRAFS classification system, which subdivides GPCRs into five discrete families: glutamate, rhodopsin, adhesion, frizzled/taste2 and secretin receptors. The adhesion-GPCR family 2 can be further subdivided into eight groups. The field of adhesion-GPCR biology has indeed become large enough to require a volume dedicated solely to this field. The contributors to this book have made a courageous effort to address the key concepts of adhesion-GPCR biology, including the evolution and biochemistry of adhesion-GPCRs; there are extensive discussions on the functional nature of these receptors during development, the immune response and tumourgenesis. Finally, there are chapters dedicated to adhesion-GPCR signalling, an area of intense investigation.

Excess of homocysteine, a product of the metabolism of the essential amino acid methionine, is associated with poor health, is linked to heart and brain diseases in general human populations, and accelerates mortality in heart disease patients. Neurological and cardiovascular abnormalities occur in patients with severe genetic hyperhomocysteinemia and lead to premature death due to vascular complications. Although it is considered a non-protein amino acid, studies over the past dozen years have discovered mechanisms by which homocysteine becomes a component of proteins. Homocysteine-containing proteins lose their normal biological function and become auto-immunogenic and pro-thrombotic. In this book, the author, a pioneer and a leading contributor to the field, describes up-to date studies of the biological chemistry of homocysteine-containing proteins, as well as pathological consequences and clinical implications of their formation. This is a comprehensive account of the broad range of basic science and medical implications of homocysteine-containing proteins for health and disease.

Origins and Principles of Clinical Biomechanics in Human Locomotion discusses key concepts of how biomechanics links to the development of pathology through mechanical laws, anatomy, physiology and health. It provides fundamental principles and practical data, and guidance of how to apply these in the clinical biomechanics field. Coverage includes: major joint movement, muscle action around joints, physiology and patho-physiology of bone, muscle and neurologic disorders. This reference is ideal for teaching students in biomechanics, orthopedics and physiotherapy. It should also be of interest to product development engineers, rehabilitation engineers, those working in prosthetics and orthotics, physiotherapists and occupational therapists. The authors explore the simple laws of motion as applied to anatomy and physiology, in order to help readers understand human pathology within the human lower limb and mobility. They then go on to look at materials science concerns within this field, such as engineering stresses and strains, principles and types of material properties and the shaping of structural properties. Readers will also find within this book information on tissue science, force generation, biological sciences, evolution in biomechanics, human gait, functional units of the lower limb and foot, and finally pathomechanical principles; all as applied to clinical biomechanics.

Introduction to Pathophysiology for Nurses and Healthcare Professionals is the most comprehensive visual survey of pathophysiology affecting each body system. Using full colour illustrations, photographs and learning features, this book makes the potentially complex subject of pathophysiology interesting and accessible. Each chapter discusses the common pathologies for each body system, along with the prevalence of the disease in the UK. The text is aimed at students and healthcare professionals who are learning about applied pathophysiology and related pharmacology and is an ideal introduction to the subject, enabling care to be based on a sound foundation of what is going on in the body.

Many complex molecular interactions are involved in the development of the mammalian brain. Molecules serving as guidance cues for migratory cells, growing axons and for recognition of postsynaptic targets are a major topic for research because they are directly involved in the formation of neuronal circuits, thus creating the foundation for subsequent functional refinement through interactions with the environment. In addition, most guidance cue molecules are also involved in plasticity, damage repair and regeneration in the adult brain. This volume reviews current knowledge on major classes of molecules involved in: guidance of growing axons; tau proteins involved in the establishment of axonal polarity, outgrowth and contact recognition; gangliosides and lectins involved in neuronal migration, neurite outgrowth and contact recognition; and myelin molecules that inhibit nerve regeneration.

This book is about the theory of Hot and Cold, a mutual fundamental base of traditional medicines all around the world. The theory describes the dynamic balance state of the body on the axis of hot and cold for each individual and proposes the fact that deviation from this equilibrium is a predisposing factor for diseases. Such an approach helps practitioners to provide treatments tailored to the patient's condition, not the disease. This book, for the first time, has gathered native descriptions of Hot and Cold theory in different traditional medicines, including traditional Chinese medicine, Persian (Humoral, Unani) medicine, Ayurvedic medicine and Latin American and Caribbean medicines. After defining the common ground, contemporary research - in nutrition, pharmacology, physiology and systems biology - has been explored using scientific methodology. This work is the result of an international collaboration of more than 30 scientists and scholars with high reputations in their fields. Hot and Cold theory, as a holistic individualized approach in prevention, diagnosis and treatment, can be merged into the novel fast-paced concepts in systems biology and precision medicine. Through this bridge, the authors propose that the Hot and Cold theory should be revisited more deeply by medical scientists, who are the main audience of this book, to pave the way towards integrated holistic personalized medicine.

Most of the progress in cardiac energetics in recent years has been spurred by the pressure-volume area concept, the natural extension into energetics of earlier pioneering work delineating the time-varying elastance framework for ventricular contraction. The book draws together a broad spectrum of researchers - basic, applied and clinical - having a shared interest in the energetics of cardiac muscle and ventricle, providing an overview of the current state of the art.

The problem of the long-term proliferation of cells is a seminal one. It has always been a hot subject in biology, a source of far-reaching hypotheses, even more so now when explanations for the mechanisms of cell prolifera tive mortality or immortality seem within our reach. A question which is still debated is whether an infinite division potential can be a normal trait or is always the result of modifications leading to abnormal cell growth and escape from homeostasis. In general, investigators have been advocates of one of the two extremes, universal limited or unlim ited normal proliferative potential. Since the long-term proliferative potential of cells concerns regulation of development, regeneration of tissues, and homeostatic control of cell growth, in brief survival of living organisms, and since the regulation of these processes is so different along the evolutionary scale, it is not surpris ing that there does not seem to be any universal trait. The question of whether cells are endowed with finite or infinite prolifera tive phenotypes has to be seen using the perspective of comparative biology."