Lactoferrin is an iron-binding glycoprotein belonging to the transferrin family. It acts as a defense in host animals against microbes and viruses, since it has a broad spectrum of antimicrobial and antiviral activities. Lactoferrin has been shown to regulate the growth and differentiation of many types of cells. The results of recent studies indicate that lactoferrin is a potent regulator of dermal fibroblasts, and promotes cutaneous wound healing. The collagen gel contraction, a model of wound contraction during wound healing process, and migration of human fibroblasts were enhanced by lactoferrin. LRP-1 (LDL Receptor related Protein-1) acts as a signaling receptor for lactoferrin that mediate fibroblast response to lactoferrin by activating ERK/MAPK signaling pathway. In addition, lactoferrin promotes biosynthesis of extracellular matrix (ECM) component such as type-I collagen and hyaluronan. Hyaluronan is a major component of ECM in connective tissue and promotes wound healing. The promoting effect of lactoferrin on hyaluronan production was accompanied by promotion of HAS2 (hyaluronan synthase 2) expression. These observations suggest that lactoferrin promotes the wound healing by providing an ECM that promotes fibroblast migration. Lactoferrin is also known for its anti-inflammatory and immune modulating properties. According to recent in vivo study, lactoferrin promotes wound repair by promoting the early inflammatory phase of wound healing. Based on this, recombinant human lactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective. Lactoferrin should be further evaluated in patients with diabetic and other types of ulcers.

F. Schweda and A. Kurtz: Regulation of Renin Release by Local and Systemic Factors M. Krauss and V. Haucke: Shaping Membranes for Endocytosis B.M. Jockusch and P.L. Graumann: The Long Journey: Actin on the Road to Pro- and Eukaryotic Cells B. Colsoul, R. Vennekens and B. Nilius: Transient Receptor Potential (TRP) Cation Channels in Pancreatic ss cells

This book presents the latest findings in the field of investigation of molecular mechanisms of mechanical stretch and the role of cytokines in response of different tissues to it. On the one hand this Volume demonstrates how mechanical stretch enhances cytokines production. It describes how cytokines influence tissues and cells on a background of a mechanical stretching. It provides a description of how cells in different tissues are activated by stretch and cytokines via various signaling pathways, and how they change their gene expression. The book is a unique collection of reviews outlining current knowledge and future developments in this rapidly growing field. Knowledge of biomechanics, and mechanisms which underlie it on molecular, cellular and tissue, is necessary for understanding of the normal functioning of living organisms and allows to predict changes, which arise due to alterations of their environment.

Cardiovascular disease is the leading cause of morbidity and premature death of modern era medicine. It is estimated that approximately 81 million people in the United States (US) currently have one or more of the many forms of cardiovascular disease, resulting in 1 in every 2.8 deaths, or 900,000 deaths per year. 40% of all deaths in Europe are a result of cardiovascular disease in people under the age of 75. Aneurysms form a significant portion of these cardiovascular related deaths and are defined as a permanent and irreversible localised dilation of a blood vessel greater than 50% of its normal diameter. Although aneurysms can form in any blood vessel, the more lethal aneurysms develop in the cranial arteries, and in the thoracic aorta and abdominal aorta. Frequently aneurysms are undetected and if left untreated may eventually expand until rupture with very high levels of morbidity and mortality. The biomechanics and mechanobiology of aneursymal diseases are not fully understood and this monograph aims to provide new insights into aneurysm aetiology and behavior based on the most recent biomechanics research related to this important topic. The contributors to this volume bring together a unique blend of expertise in experimental, computational and tissue biomechanics relating to aneurysm behavior and enable the reader to gain a fresh understanding of the key factors influencing aneurysm behavior and treatment. Biological risk factors such as tobacco smoking, sex, age, hypertension, family history and mechanobiological risk factors such as aneurysm geometry and shape as well as mechanical properties of the diseased tissues are considered in detail as are many of the diagnostic and treatment options.

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!

This book is intended for undergraduates studying the biological and medical sciences. The field of excitable cell physiology is one which is found quite baffling by a significant minority of these students. My aim here is to provide a brief introductory account, based on a conceptual approach, rather than on a mathematical or historical description. Once the student has grasped certain basic ideas concerning excitable cell function, the individual examples which follow fit into a well-defined pattern. No attempt has been made to give credit in appropriate measure to the many scientists who have contributed to this field. The further reading cited has been chosen with the reader alone in mind. I would like to thank Tim Cripps for help and advice, also Charlie Tomson and Michael Hart for their careful reading of the manuscript. Finally I am indebted .to Jenny Kenyon for her excellent typing of the work. Part One THE CONCEPT OF EXCITABILITY INTRODUCTION 1 1.1 The Excitable Tissues living organisms are able to respond to changes in their environment."

This book provides readers with an anaesthesia-focused alternative to general physiology textbooks. The new edition has been reorganised with the trainee anaesthesist in mind, into shorter bite-sized chapters ideal for exam revision. The content includes the physiology of all major organ systems, with specific emphasis on the nervous, respiratory, and cardiovascular systems as well as special sections on pain, aging, specific environments and obesity. Alongside the learning objectives, reflection points and a handy summary of physiological equations and tables, there is greater emphasis on clinical application in this fourth edition, with applied physiology included in almost every section.

This book offers a mathematical update of the state of the art of the research in the field of mathematical and numerical models of the circulatory system. It is structured into different chapters, written by outstanding experts in the field. Many fundamental issues are considered, such as: the mathematical representation of vascular geometries extracted from medical images, modelling blood rheology and the complex multilayer structure of the vascular tissue, and its possible pathologies, the mechanical and chemical interaction between blood and vascular walls, and the different scales coupling local and systemic dynamics. All of these topics introduce challenging mathematical and numerical problems, demanding for advanced analysis and efficient simulation techniques, and pay constant attention to applications of relevant clinical interest. This book is addressed to graduate students and researchers in the field of bioengineering, applied mathematics and medicine, wishing to engage themselves in the fascinating task of modeling the cardiovascular system or, more broadly, physiological flows.

The workshops that have been held over the past few years and the volumes published in their wake have proved highly successful and have prompted us to press on with our initial plans. Our basic aim was to tackle certain very important problems in respiratory rehabilitation and then discuss the various issues with people from all over the wodd engaged in the updating of experience and know ledge in this field. We therefore firmly believe that this ongoing effort is of fundamental importance. Hyperinflation, which is still a poody defined c1inical and physiopatho logical condition, is the focal point ofthis present study, which is aimed at discussing and weighing up the physiopathological mechanisms, c1inical consequences, and rehabilitation possibilities in a disease in which, until relatively recently, rehabilitation had seemed almost totally ineffective. The present contributions, however, show us how very important and versatile rehabilitation may be in its treatment. Perhaps, if we consider this branch of medicine as one which now no longer simply draws upon other sciences, but make an active contribution in its own right, we will have touched upon the most important aspect of this study. If I may, I would just like to add how very pleasing it is for me to acknow ledge how much this joint effort has contributed, in terms of true insights and above all VI results, to finding solutions to the problems addressed in reeent years.

This well-established and acclaimed textbook introducing the rapidly growing field of nerve and muscle function has been completely revised and updated. Written with undergraduate students in mind, it begins with the fundamental principles demonstrated by the pioneering electrophysiological experiments on cell excitability. This leads to more challenging material recounting recent discoveries from applying modern biochemical, genetic, physiological and biophysical, experimental and mathematical analysis. The resulting interdisciplinary approach conveys a unified contemporary understanding of nerve and skeletal, cardiac and smooth muscle function at the molecular, cellular and systems levels. Emphasis on important strategic experiments throughout clarifies the basis for our current scientific views, highlights the excitement and challenge of biomedical discovery, and suggests directions for future advances. These fundamental ideas are then translated into discussions of related disease conditions and their clinical management. Now including colour illustrations, it is an invaluable text for students of physiology, neuroscience, cell biology and biophysics.

Stress-induced myocardial ischemia is a frequent manifestation of coronary heart disease, and sympathetic activation is an important precipitating and aggravating factor in such stress- induced ischemia. However, the complex interplay between the sympathetic initiation of myocardial ischemia, ischemia-induced alterations in sympathetic neurotransmission, as well as changes in adrenoceptor density and post-receptor signal transduction that can occur during ischemia remains incompletely understood. Not only the activation of myocardial fJ- adrenoceptors, but also the activation of coronary IX-adrenoceptors can contribute to myocar- dial ischemia. However, the role of fJ-adrenoceptor-mediated increases in contractility relative to heart rate in the initiation of ischemia is not clear, and the significance of IX-adrenoceptor- mediated changes in coronary vasomotor tone, as well as the responsible IX-adrenoceptor subtypes are highly controversial. Malignant arrhythmias may be triggered by both IX- and fJ-adrenergic mechanisms. Current research in this field is focussed not only on the underlying physiological and pathophysiological mechanisms, but also on clinical treatment strategies, e. g. , by fJ-blockade, IX-blockade, bradycardic agents and calcium antagonists. Recent findings were presented and future research directions discussed during the 61" International Titisee Conference, held at the Schwarzwald-Hotel, Titisee, March 29-31, 1990 under the sponsorship of the Boehringer Ingelheim Foundation. Dr. Hasso Schroeder and Dr. Hermann Frohlich deserve special thanks for their generous support and pleasant organization of the meeting. The publication of the proceedings has been made possible by grants from Astra Chemicals, Bayer, ICI, Dr. Karl Thomae, and Upjohn.

W. Ulbricht: Effects of veratridine on sodium currents and fluxes. W. Meyerhof: The elucidation of somatostatin receptor functions: a current view.M. Leist, F. Gantner, g. Kunstle and A. Wendel: Cytokine-mediated hepatic apoptosis.

The objectives in this special issue are (1) to critically review current information on the mechanisms coupling extracellular regulatory signals to regulation of cross-bridge cycling and proliferation in smooth muscle, and (2) identify significant gaps or unresolved issues that are important topics for future research. The experimental and analytical difficulties discussed above are increasingly recognized and surmounted. Elucidation of the molecular and cellular events underlying the biologal properties of smooth muscle is in the midst of a period of rapid progress. While the reviews reveal many gaps to be filled and illustrate areas of contention, they also capture the excitement of new discoveries.

This book deals with information processing in the primate temporal visual cortex, one of the higher visual association areas, which is believed to be important for the representation of complex stimuli and may also play a role in visual memory. Here, the need for rapid information processing shapes the functional architecture of all sensory systems, acting to reduce, where possible, wiring length and the number of synapses, to allow faster processing.

Assessment of cardiac energetics at the level of ATP-synthesis, chemomechanical energy transformation and whole organ dynamics as a function of haemodynamic load, ventricular configuration and oxygen- and substrates supply is basic to understanding cardiac function under physiological and pathophysiological (hypertrophy, hypoxia, ischaemia and heart failure) conditions. Moreover, cardiac energetics should be an important consideration in the choice and application of drugs especially in the case of vasodilators, inotropic agents and in cardioprotective measures. Only by considering energetics at the subcellular, cellular, and whole-heart level we can arrive at a better understanding of cardiac performance and ultimately better clinical judgement and drug therapy. Quantification of myocardial energetics will also help to determine the optimal time for surgical interventions such as valvular replacement or aneurysm resection. The present volume is the outcome of an international symposium on cardiac energetics held in Gargellen/Montafon (Austria), June 1986. The contributions will certainly help bridge the existing gap between basic research involving isolated structures and that involving the whole organ, on the one hand, and render the results derived from basic research applicable to clinical problems, on the other hand.

Ischemie heart disease is still the most frequent cause of death in the western world. There have been significant achievements in diagnostic procedures as well as in the medical, invasive,and surgiealtreatment ofischemieheart disease inrecent years. A variety ofdrugs are availablefor the pharmacotherapyofischemieheart disease,par- ticularly nitrates, ss-blockers, and calcium-antagonists which are used as mono- therapy or in various combinations. However, the selection of patients for a certain treatment, as weIl as the optimization of an individual treatment are still largely empirical. On the other hand, the recent advances in experimental cardiology emphasize the extremely complex and dynamie scenario of ischemic heart disease, involving endothelial damage, coagulation processes, metabolie and morphologie derangements, coronary constrictor mechanisms, blood flow redistribution, arrhythmogenesis, contraetile dysfunction during ischemia and reperfusion, and finally lack or presence of pain perception. Therefore, it appears desirable to close the gap between experimental and clinical cardiology and, thus, to provide a pathophysiologieal basis for rational cliniealdecisions with respect to diagnostic and therapeutic procedures. The idea for this book arose during the preparation of a seminar series on experi- mental cardiology, when I found it diffieultto collect the pertinentinformation from textbooks of cardiology, physiology, pathology, and pharmacology, as well as from numerous review and original artieies on specifictopies. I am now very grateful that expert cliniealand experimental colleagues from around the world have joined me in the effort to provide a comprehensive textbook on the pathophysiology of myocar- dial ischemia and its rational pharmacotherapy.

The study of membrane traffic in reconstituted cell-free systems has generated an unprecedented amount of new information on the biochemistry, molecular biology and genetics of membrane-based molecular events that underly normal and abnormal cellular function. Many of the individual steps have now been isolated and dissected in simple systems that permit detailed molecular analyses of transport mechanisms and their regulation. Reconstituted events of intercompartment transport include inter-membrane recognition, and controlled membrane fusion-fission reactions. Among the many advances is the growi ng awareness of a remarkabl e evolutionary conservation of many of the components involved in the many steps of membrane traffic, this realization has accelerated greatly the pace of progress in the field. This book provides a collection of participant contributions from the 1992 Summer Research Conference, "Mol ecul ar Mechani sms of Membrane Traffi c, " jointly sponsored with NATO by the American Society of Cell Biology. The conference was held May 9-13, at the Airlie Conference Center in the Virginia countryside, near Warrenton. The conference was attended by 158 scientists. A unique feature was the high proportion of young scientists among the participants. Approximately 65% were students, postdoctoral fe 11 ows and young investigators. Each attendee contri buted to the conference with either a pl atform or poster presentation.

In the last two decades, our knowledge on regulatory peptides and their cognate receptors, most of which are members of the seven transmembrane receptor families, has increased enormously. Regulatory peptides are small proteins which, besides their hormonal functions in regulating cellular metabolism in various tissues, may also act as neurotransmitters, and thus they often carry the prefix "neuro." Many of the cognate receptors involved in transducing the peptidergic signal across the cell membrane via a family of G proteins exist in multiple forms, the number of which frequently exceeds that of the corresponding peptide ligands. In this book, various peptide-receptor systems are discussed, e.g. CRF, somatostatin, TRH, opioid peptides, vasopressin, and oxytocin. It also discusses new strategies such as "reverse physiology" to uncover new peptides and orphan receptors.

(Chapters 11 to 14) summarise important features of the biological clock at the level of whole animal covering all vertebrate classes (fish to mammal). Chapters 15 and 16 are on long term (seasonal) rhythms in plants and higher vertebrates. Short term rhythms (ultradian rhythms), the significance of having a clock system in animals living in extreme (arctic) environments, and the diversity of circadian responses to melatonin, the key endocrine element involved in regulation of biological rhythms, have been discussed in Chapters 17 to 19. Finally, a chapter on sensitivity to light of the photoperiodic clock is added which, using vertebrate examples, illustrates the importance of wavelength and intensity of light on circadian and non-circadian functions. A well-known expert writes each chapter. When presenting information, the text provides consistent thematic coverage and feeling for the methods of investigation. Reference citation within the body of the text adequately reflects the literature as subject is developed. A chapter begins with an abstract that enables a reader to know at the first glance the important points covered in that chapter. The chapter concludes with a full citation of references included in the text, which could be useful for further reading. The book ends with a comprehensive subject index that may be useful for quick searches.

The four contributions by Ishibashi et al., Klussmann et al., Zeuthen and Larsen et al. summarize the current knowledge on the molecular mechanisms underlying the short and long term regulation of water channels (AQPs) in principal cells, fluid transport by leaky epithelia and cotransporters of the symport type which behave as molecular water pumps.

Special Issue on the Tird Filament System

Many unexplored complex cellular and organismal adaptations occur in response to the stress of alcohol exposure, and its contribution to the development of chronic diseases, such as osteoporosis, heart disease and diabetes, is particularly relevant today, given the increased incidence of these diseases in our aging population. In Alcohol: Methods and Protocols, the pleiotropic effects of ethanol in animal and cell culture models are rigorously examined through a collection of detailed procedures written by experts in the field. Sections present clearly defined models of ethanol exposure, recent advances in the development of specific methodologies to mimic the impact of ethanol metabolism in cultured cells, and methodologies to investigate a variety of cells and tissues that are known to be disrupted by ethanol, amongst other topics.