Organs and tissues that can tolerate little or no inflammation have developed multiple overlapping mechanisms of immune protection in the absence of inflammation. These areas have been designated immune-privileged sites by Peter Medawar and include the central nervous system, eye, reproductive tract, testis and possibly the liver. Mechanisms of immune homeostasis found in less immune-regulated organs are often evident in the immune privileged sites and vice versa. It is important that the non-inflammatory mechanisms that contribute to immune privilege allow host defense against infectious organisms.

This volume highlights the mechanisms leading to immune privilege in tissues and organs, the deviation of immune responses and the modification of the behavior of the immune cells that manage to cross the blood barriers of tissues, in the context of infection.

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This book offers a comprehensive study of biological molecules acquired from marine organisms, which have been exploited for drug discovery with the aim to treat human diseases. Biomolecules have potential impacts on a diverse range of fields, including medical and pharmaceutical science, industrial science, biotechnology, basic research, molecular science, environmental science and climate change, etc. To understand and effectively apply medicinally important biomolecules, multidisciplinary approaches are called for. The ocean remains a rich biological resource, and the vast untapped potential of novel molecules from marine bio-resources has caught the interest of more and more researchers. These novel biological compounds have never been found in terrestrial or other ecosystems, but only in this rich niche. Advances in sampling techniques and technologies, along with increased funding for research and nature conservation, have now encouraged scientists to look deeper in the waters. Aquaculture supports both tremendous seafood production and the bulk production of marine-derived drugs. Furthermore, molecular methods are now being extensively employed to explore the untapped marine microbial diversity. With the help of molecular and biotech tools, the ability of marine organisms to produce new biosynthetic drugs can be greatly enhanced. This book provides an extensive compilation of the latest information on marine resources and their undisputedly vital role in the treatment of diverse ailments.

The study of electrochemical nanotechnology has emerged as researchers apply electrochemistry to nanoscience and nanotechnology. These two related volumes in the Modern Aspects of Electrochemistry Series review recent developments and breakthroughs in the specific application of electrochemistry and nanotechnology to biology and medicine. Internationally renowned experts contribute chapters that address both fundamental and practical aspects of several key emerging technologies in biomedicine, such as the processing of new biomaterials, biofunctionalization of surfaces, characterization of biomaterials, discovery of novel phenomena and biological processes occurring at the molecular level.

During the last decade we have witnessed a rapid expansion of our knowledge of the role of the endothelium in the control of vascular tone and hemostasis. In paricular, developments in molecular biology have enabled us to understand its physiology in greater detail. Furthermore, it is now clear that dysfunction of the endothelium contributes to various cardiovascular diseases. This is especially true for the coronary vascular bed. Development of atherosclerosis, disturbed vasomotor tone in stable ischemic syndromes, and the interaction of thrombocytes with the endothelium in acute ischemic syndrome are all consequences of endothelium dysfunction. Also, secondary changes in endothelial function have been described, for instance in chronic heart failure. This monograph reviews the present knowledge of the role of the endothelium in the control of coronary flow. The authors lead the reader through this topic starting at the basic physiology of endothelial function and the principles of coronary flow regulation. Next, the use of modern clinical techniques to evaluate endothelial function such as positron emission tomography and angioscopy are discussed. Subsequently, several pathophysiological processes and the role of endothelium are addressed. Finally, the interaction of various presently used cardiovascular drugs with the endothelium is indicated. It is the combination of basic sciences with clinical observations in this book which may be appreciated by a large number of scientists and physicians active in the field of cardiovascular disease. It is also this combination of different disciplines which will determine future developments and new avenues in pharmacotherapy involving the endothelium.

Since its identification by Sir Henry H. Dale a century ago, histamine has become one of the most important multifunctional biogenic amines in the field of biomedicine. The pharmacological effects of histamine are mediated through four types of membrane histamine receptors; H1R, H2R, H3R and H4R, which are all heptahelical G-protein-coupled receptors. It has been known to play the broadest spectrum of activities in various physiological and pathological conditions including cell proliferation, differentiation, hematopoiesis, embryonic development, regeneration, wound healing, aminergic neurotransmission and numerous brain functions, secretion of pituitary hormones, regulation of gastrointestinal and circulatory functions, cardiovascular system, as well as inflammatory reactions, modulation of the immune response, endocrine function and homeostasis, and other important areas. This book is a compendium of the current state of established and investigational literature on Histamine, its receptors and their Agonists and antagonists. It provides a comprehensive overview of histamine biology in the field of biochemistry, cell biology, molecular biology, immunology, allergy, neurobiology, pharmacology, microbiology and reproductive biology. The first section on Histamine biology and physiology leads into subsequent sections on enzymology, pharmacology, regulation of the immune system and cell proliferation and role in allergic and other diseases including acid peptic diseases, inflammatory diseases, autoimmune and cancer diseases, nervous system, reproductive functions and hematopoiesis. The compilation of chapters in the book presents the most recent advances in histamine research and bridges the basic and clinical aspects of histamine biology.

Tony Seed, Gilbert Thompson, Jackie Downs and John MacDermot at the book's launch in LondonThis book brings together in one volume fifteen Nobel Prize-winning discoveries that have had the greatest impact upon medical science and the practice of medicine during the 20th century and up to the present time. Its overall aim is to enlighten, entertain and stimulate. This is especially so for those who are involved in or contemplating a career in medical research.Anyone interested in the particulars of a specific award or Laureate can obtain detailed information on the topic by accessing the Nobel Foundation's website. In contrast, this book aims to provide a less formal and more personal view of the science and scientists involved, by having prominent academics write a chapter each about a Nobel Prize-winning discovery in their own areas of interest and expertise.

This book focuses on issues in clinical practice and research that are of general interest. The articles primarily focus on understanding the pathogenic mechanisms of diseases, their prevention, and therapy. The topics addressed include cardiovascular regulation with regard to blood pressure and heart rate variability, and to coupling blood pressure changes with subarachnoid fluid oscillations. In addition, the book discusses recent advances in the diagnostics of and targeted molecular therapy for renal and pancreatic malignancies, growth disorders, vitamin D and calcium homeostasis in children in the context of neonatal urolithiasis, and neurosurgical interventions in multifarious age-related diseases of the vertebrae. Neuropsychological aspects of patients' quality of life and of shaping medical staff's attitude toward patients are also addressed. The respective articles are intended to build a bridge between basic and clinical research. Further, the book enhances the current body of knowledge on diagnostics and patient treatment and offers valuable new perspectives on practical clinical issues. As such, it offers a unique resource for clinicians, family physicians, medical scholars, and professionals engaged in patient management.

In the coming decade, the focus of medicine will shift from a disease-oriented approach, where the physician prescribes according to the disease the patient has, to a personalized approach, in which the physician first considers the patient's individual biochemistry before prescribing a treatment. Personalized medicine has the potential to improve efficacy and safety in virtually all fields of medicine. Unfortunately, few physicians feel confident in their ability to apply the principles of genetics and genomics upon which personalized medicine is based to their practice. This book is intended to help the practicing physician understand and apply the principles of genetic and genomic medicine, regardless of his/her level of background in the field. It provides a thorough foundation/review of classical genetic principles, with an emphasis on how these principles apply to personalized medicine and common complex diseases. In addition, it provides a wide-ranging review of the inroads that personalized medicine has made into several fields, including cancer, psychiatric disorders, cardiovascular disease, substance abuse, Alzheimer disease, respiratory diseases, type 2 diabetes and macular degeneration. Most importantly, this book is intended to enable the practicing physician, physician assistants and their entire healthcare team to anticipate the developments that will emerge in the near future, and stay current with the field as it expands.

The combination of molecular biology, engineering and bioinformatics has revolutionized our understanding of cancer revealing a tight correlation of the molecular characteristics of the primary tumor in terms of gene expression, structural alterations of the genome, epigenetics and mutations with its propensity to metastasize and to respond to therapy. It is not just one or a few genes, it is the complex alteration of the genome that determines cancer development and progression. Future management of cancer patients will therefore rely on thorough molecular analyses of each single case. Through this book, students, researchers and oncologists will obtain a comprehensive picture of what the first ten years of cancer genomics have revealed. Experts in the field describe, cancer by cancer, the progress made and its implications for diagnosis, prognosis and treatment of cancer. The deep impact on the clinics and the challenge for future translational research become evident.

Prevention of infectious diseases by vaccination is one of the most significant achievements of modern medicine. During the 20th century, the average human life span in the developed world was about 70 years and it is expected to increase, with a significant portion of this increase directly attributed to vaccination. Since the first empiric vaccination trials, knowledge and technology have enormously evolved and new vaccination strategies are emerging on the market. Indeed, in spite of the great success, conventional vaccination strategies sometimes may result ineffective and, above all, may raise safety concerns. The aim of this book is to provide an overview of some of the technology platforms that have been realized or are currently under development to try to address unsolved and new issues in the field of vaccine development. Common denominator of all thematic areas described herein is the multidisciplinary teamwork. Most of the enabling technologies have been established by putting in the "melting pot" expertise in fields that, at first glance, may appear very far apart. I hope that this collection of articles will make the readers aware that vaccinology is rapidly taking a new direction, ceasing to be an empirical science.

Investigation of the mechanisms of cellular response to different mechanical stimuli, as well as mechano-electrical feedback (MEF) in the intact heart is one of the main topics in fundamental and clinical cardiology. The present volume of "Mechanosensitivity in Cells and Tissues: Mechanosensitivity of the Heart" c- bines excellent reviews written by worldwide leaders in this ?eld. The 3rd volume is a great addition to this excellent series of books edited by Andre Kamkin and Irina Kiseleva. This volume successfully combines reviews, aimed at academic, physiology and clinical cardiology communities, devoted to mechanosensitivity of the normal and diseased heart at the ion channel, cell, tissue and organ levels. Kamkin and Kiseleva have made signi?cant contributions to the investigation of mechanosentive ion channels in cardiomyocytes and ?broblasts. Their ba- ground, in addition to extensive collaborations helped them to ?nd and consolidate valuable research ?ndings from prominent specialists in the ?eld of cardiac mechanosensitivity. In the last decade, interest in the role of MEF in the heart has increased sign- cantly. MEF within cardiac tissue is a complex phenomenon in which electroph- iological changes are triggered by myocardial stretch. This phenomenon has been studiedintheclinicalcommunityforoveracenturyandmayhavebothpro-rhythmic and arrhythmogenic consequences. While signi?cant advances have been made in understanding of the effects of mechanical forces on cardiac cells, many questions remain regarding the mechanisms whereby mechanical forces are transduced into changes which alter the behavior of various cardiac cells.

Oligonucleotides represent one of the most significant pharmaceutical breakthroughs in recent years, showing great promise as diagnostic and therapeutic agents for malignant tumors, cardiovascular disease, diabetes, viral infections, and many other degenerative disorders. The Handbook of Analysis of Oligonucleotides and Related Products is an essential reference manual on the practical application of modern and emerging analytical techniques for the analysis of this unique class of compounds. A strong collaboration among thirty leading analytical scientists from around the world, the book provides readers with a comprehensive overview of the most commonly used analytical techniques and their advantages and limitations in assuring the identity, purity, quality, and strength of an oligonucleotide intended for therapeutic use. Topics discussed include: Strategies for enzymatic or chemical degradation of chemically modified oligonucleotides toward mass spectrometric sequencing Purity analysis by chromatographic or electrophoretic methods, including RP-HPLC, AX-HPLC, HILIC, SEC, and CGE Characterization of sequence-related impurities in oligonucleotides by mass spectrometry and chromatography Structure elucidation by spectroscopic methods (IR, NMR, MS) as well as base composition and thermal melt analysis (Tm) Approaches for the accurate determination of molar extinction coefficient of oligonucleotides Accurate determination of assay values Assessment of the overall quality of oligonucleotides, including microbial analysis and determination of residual solvents and heavy metals Strategies for determining the chemical stability of oligonucleotides The use of hybridization techniques for supporting pharmacokinetics and drug metabolism studies in preclinical and clinical development Guidance for the presentation of relevant analytical information towards meeting current regulatory expectations for oligonucleotide therapeutics This resource provides a practical guide for applying state-of-the-art analytical techniques in research, development, and manufacturing settings.

The series Topics in Current Chemistry presents critical reviews of the present and future trends in modern chemical research. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field.

This book covers topics that range from fundamental studies of DNA replication, chromosomal and nuclear function through growth factor control of endocrine tumor initiation and progression. The basic and translational insights gained from Hormonal Control of Cell Cycle will be of interest to those studying the biology of endocrine tumors as well as those deriving novel therapeutic approaches for these benign and malignant disorders.

"Bio-Farms for Nutraceuticals" can be said to have been born of the NUTRA-SNACKS project within the Sixth Framework Programme Priority on Food Quality and Safety. One objective of NUTRA -SNACK S was to improve the nutritional and eating properties of ready-to-eat products and semi-prepared foodstuffs through better monitoring of the quality and safety of raw materials and the development of innovative processes along the production chain. Another main objective of the project was the production of ready-to-eat snacks with high nutraceutic activity. Seven research institutes and three companies in six European countries were involved in this effort. The co-operation resulted in the production of food having a high content of natural metabolites with the following beneficial health effects: anticancer, antilipidemic, anticholesterol, antimicrobial, antibacterial, antifungal, antiviral, antihypertensive, anti-inflamatory and antioxidant activities.

Part I The Nano-Scale Biological Systems in Nature; Molecular bio-motors in living cells - by T. Nishizaka; The form designed by viral genome - by K. Onodera; Part II Detection and Characterization Technology; Atomic force microscopy applied to nano-mechanics of the cell - by A. Ikai; Design, synthesis and biological application of fluorescent sensor molecules for cellular imaging - by K. Kikuchi; Dynamic visualization of cellular signaling - by Q. Ni and J. Zhang; Part III Fabrication Technology; Surface acoustic wave atomizer and electrostatic deposition - by Y. Yamagata; Electrospray deposition of biomolecules by V.N. Morozov; Part IV Processing Technology; Droplet handling - by T.Torii; Integrated microfluidic systems - by S. Kaneda and T. Fujii; Part V Applications; A novel non-viral gene delivery system: Multifunctional envelope-type nano device - by H. Hatakeyama, H. Akita, K. Kogure, and H. Harashima; Biosensors - by M. Saito, H.M. Hiep, N. Nagatani, and E.Tamiya; Micro bioreactors - by Sato and T. Kitamori

The pace of new research and level of innovation repeatedly introduced into the field of drug delivery to the lung is surprising given its state of maturity since the introduction of the pressurized metered dose inhaler over a half a century ago. It is clear that our understanding of pulmonary drug delivery has now evolved to the point that inhalation aerosols can be controlled both spatially and temporally to optimize their biological effects. These abilities include controlling lung deposition, by adopting formulation strategies or device technologies, and controlling drug uptake and release through sophisticated particle technologies. The large number of contributions to the scientific literature and variety of excellent texts published in recent years is evidence for the continued interest in pulmonary drug delivery research. This reference text endeavors to bring together the fundamental theory and practice of controlled drug delivery to the airways that is unavailable elsewhere. Collating and synthesizing the material in this rapidly evolving field presented a challenge and ultimately a sense of achievement that is hopefully reflected in the content of the volume.

For many years, the authors have investigated the adaptive role of heat shock proteins (HSPs) in different animals, including the representatives of homothermic and poikilothermic organisms that inhabit regions with contrasting thermal conditions. This book will summarize the data accumulated in the course of these studies and describe the general molecular mechanisms underlying the adaptation of various organisms to aggressive environments. We also concentrate on different evolutionary trends characteristic for HSP systems in the course of adaptation to fluctuating environmental conditions. In addition, we describe the peculiarities in the regulatory regions of heat shock genes necessary for fine tuning of these systems providing the adaptation to adverse conditions. Special emphasis is given to the role of mobile elements in the evolution and functioning of various groups of HSP genes. The book combines the results of field studies and laboratory analysis of stress genes systems.

Resistance to chemotherapy, and especially multi-drug resistance, represents a significant barrier to the successful treatment of cancer. This multi-author volume brings together a wide range of up-to-date reviews on different aspects of our knowledge of drug-resistance mechanisms, written by experts in the different areas. Particular attention is paid to recently discovered mechanisms relating to oncogene expression and in particular to proteins involved in regulation and execution of apoptosis. Other important topics covered include DNA repair, topoisomerases, cell cycle control, oxygenation and vascularisation of tumours, LRP, intermediate filament proteins and low-level resistance. Recent developments in understanding the role of efflux pumps (P-170, MRP) in multi-drug resistance are also reviewed. This book will be useful to clinicians and scientists working in the areas of chemotherapy, drug resistance, DNA repair and apoptosis research.

Streptococci are Gram-positive bacteria that cause a wide spectrum of diseases, such as pharyngitis, necrotizing fasciitis and streptococcal toxic shock syndrome, as well as rheumatic fever and rheumatic heart disease as sequelae. Antibiotics alone have not been able to control the disease and in spite of many efforts an effective vaccine is not yet available. A prerequisite for novel and successful strategies for combating these bacteria is a complete understanding of the highly complex pathogenic mechanisms involved, which are analyzed in this volume. In ten chapters, prominent authors cover various aspects including streptococcal diseases and global burden, epidemiology, adaptation and transmission, and molecular mechanisms of different diseases, as well as sequelae, vaccine development and clinical management. This book will serve as a valuable reference work for scientists, students, clinicians and public health workers and provide new approaches to meeting the challenge of streptococcal diseases.

Circumcision affects 15.3 million children and young adults annually. In terms of gender, 13.3 million boys and 2 million girls are subjected to the involuntary removal of part or all of their external sexual organs every year. The problem of female circumcision has been addressed on an international level, but male circumcision remains a controversial subject that many academics have been reluctant to examine. Circumcision is tolerated today because it has been practiced for millennia by a small but vocal minority of religious and ethnic groups, however, when the practice is examined through the lens of modern legal, ethical, and human rights advancements, no place remains in civilized society for this body-altering ritual. In Genital Autonomy: Protecting Personal Choice, international experts address various types of genital modifications, the impact of these harmful traditional practices on the child, on human rights, and on the development of the concept of bodily integrity. The papers presented in this volume address these topics from a variety of angles. They question and dissects the true motivations of the doctors, witch doctors, and "holy men" who promote and profit from circumcision.

This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton's Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.

Lessons from Animal Diabetes is a broad compendium of international research in experimental diabetes to which the authors have contributed reviews with original information and discussion. It is a valuable resource for medical researchers (both MD and PhD) and for diabetologists whose activities lie at the crossroads of endocrinology, immunology, physiology, biochemistry, genetics, pathology and metabolism. It is also a rich and useful reference source for graduate students in these fields. Veterinary scientists and pharmaceutical investigators testing therapeutic modalities in animals with predetermined diabetes or diabetes induced by cytotoxic or nutritional factors will also be interested in reading this volume. This is the sixth volume of a series which comprises invited reviews on subjects of contemporary interest both in IDDM and NIDDM. The contributors to the IDDM section have dealt with the expression of glutamic acid decarboxylase (GAD) and its role as antigen, the involvement of macrophages, cytokines and retroviruses in the pathogenesis of diabetes, molecular genetics of IDDM as well as new perceptions of the unified mechanisms leading to the final B-cell death as a result of cytotoxic and immune agents. There is also a section dealing with Transgenic Constructs, the new animal models rising in importance in the research of diabetes and its related phenomena. The articles devoted to this topic range from effects of B-cell function to immunomodulatory alterations and diabetic complications. The contributors to the section on the NIDDM syndrome, comprising 10 articles, deal both with new and recognized models including the spontaneously diabetic OLETF rat, Chinese hamsters, Goto-Kakizaki rats, db/db mice, rhesus monkeys, dogs, Zucker fa/fa and corpulent cp/cp rat interstrains. This book will be a valuable asset for diabetologists, endocrinologists, physiologists, veterinary scientists, pharmaceutical investigators, and graduate students.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.