It is now well known that proteases are found everywhere, in viruses and bacteria as well as in all human, animal and plant cells, and play a role in a variety of biological functions ranging from digestion, fertilization, development to senescence and death. Under physiological conditions the ability of proteases is regulated by endogenous inhibitors. However, when the activity of proteases is not regulated appropriately, disease processes can result, as seen in Alzheimer’s disease, cancer metastasis and tumor progression, inflammation and atherosclerosis. Thus it is evident that there is an absolute need for a tighter control of proteolytic activities in different cells and tissues. Aimed at graduate students and researchers with an interest in cellular proteolytic events, Role of Proteases in Cellular Dysfunctions is the second book on Proteases in this series. The book consists of three parts in specified topics based on current literatures for a better understanding for the readers with respect to their subject-wise interests. The first section of this book covers a brief idea about the neuronal disorders and the involvement of proteases such as calpains, caspases and matrix metalloproteases (MMPs). The second section covers the deadly disease cancer and its relation to ubiquitin-proteasome system, MMPs and serine proteases. The last section is about the role of proteases such as calpains, MMPs and serine protease as well as urokinase type plasminogen activator receptor (uPAR) in causing cardiovascular defects.

The unique biology of cardiac fibroblasts and related cells, such as cardiac myofibroblasts and valvular interstitial cells, distinguish them from other fibroblastic cells, a concept that is only beginning to be widely appreciated. Further, the natural signals that stimulate and inhibit cardiac fibrosis within these cells are not well understood. This volume compiles articles that address the molecular mechanisms that control the synthesis and secretion of the cardiac ECM. The book showcases chapters that highlight discussion of role of Transforming Growth Factor β (TGFβ), an important fibrogenic cytokine and its downstream effectors SMAD in many cardiac diseases. Further, the contributions highlight information to discuss endogenous inhibitors of cardiac fibrosis, as well as advances in tissue engineering specific to matrix in the heart. Finally, discussions of unifying mechanisms of matrix remodeling in valves and myocardium are presented. The mechanisms involved in the stimulation of cardiac fibrosis are not fully understood. In most cases the marginal attenuation of cardiac fibrosis as a result of a given therapy is a beneficial side-effect linked to other primary effects on other cells, especially cardiomyocytes. Very few drugs or agents are known to affect the function and dysfunction of cardiac fibroblasts and myofibroblasts alone. The book helps to translate the information gathered within to allow us to alter the course of fibrogenic events that are typical of cardiac fibrosis, and thereby reduce their burden on the patient and on society itself.

Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy, Volume, Volume 148, the latest volume in the Progress in Molecular Biology and Translational Science series covers a variety of timely topics, with chapters focusing on The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs, Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target, Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy, Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia, and Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology. This volume is the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease. It focuses on the role of MMPs in other systems, target tissues, and pathological disorders and the potential benefits of MMP inhibitors in various disorders. Serves as the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease Focuses on cardiovascular remodeling Contains contributions from leading authorities on the topics Publishes cutting-edge reviews in molecular biology

Inflammation in itself is not to be considered as a disease . . . and in disease, where it can alter the diseased mode of action, it likewise leads to a cure; but where it cannot accomplish that solitary purpose . . . it does mischief - John Hunter, A Treatise on the Blood, ITfIlammation, and Gunshot Woundr (London, 1794)1 As we reached the millennium, we recognized the gap between our scientific knowledge of biologic processes and our more limited clinical capabilities in the care of patients. Our science is strong. Molecular biology is powerful, but our therapy to help patients is weaker and more limited. For this reason, this book focuses on the problems of multiple organ failure (MOF), multiple organ dysfunction syndrome (MODS), and systemic inflammatory response syndrome is, patients who have severe injuries; require major, (SIRS) in high-risk patients, that overwhelming operations; or have serious illnesses requiring intensive care; patients who have diseases elsewhere, in other organs or systems, that limit their capabilities to survive a new insult; and patients who are elderly or at high risk for sepsis or other complications. These are the patients who need our help. They need the advances in science, in molecular biology, immunology, pathophysiology, biochemistry, genetics, high technology, and other areas of maximum support at the bedside. These advances could potentially have the greatest impact on improving patient care.

As age related diseases increase in prevalence and impact more significantly on medical resources it is imperative to understand these diseases and the mechanisms behind their progression. New research has stimulated a growing interest in mitochondrial involvement in neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis and the mechanisms which lead from mitochondrial dysfunction to neurodegeneration. Mitochondrial Dysfunction in Neurodegenerative Disorders brings together contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of these diseases, guiding the reader through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, to the consequences of this dysfunction on neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.

Hereditary or genetic diseases featuring involuntary movements constitute a major aspect of the practice of neurology, functional neurosurgery, genetics, and many areas of basic and applied neuroscience research. Describing the current knowledge on these disorders, Genetics of Movement Disorders brings together information essential for clinicians, geneticists, and neuroscientists in one source. Utilizing a convenient and accessible format, the book is designed to allow easy identification of relevant information, with the overall organization of topics following established phenotypic classifications of movement disorders such as Parkinsonian syndromes, chorea, ataxia, and major categories of diseases grouped by gene locus. This book broadly appeals to neurologists, neuroscientists, geneticists, as well as cell and molecular biologists and hematologists. - Consistently formatted to present a clinical description of the disorder, followed by an in-depth analysis of the mutation and function of the mutated gene including cellular and animal models - Emphasizes the use of DNA tests for each respective disorder - Provides up-to-date, easily accessible information for clinicians, geneticists, and neuroscientists

This book provides a comprehensive overview of the proteases involved in programmed cell death. It presents a focused yet extensive discussion on proteolytic enzymes such as caspases, HtrAs, granzymes, calpains and cathepsins as well as laboratory protocols related to enzymology and apoptosis. Mouse model systems and non-invasive imaging techniques in apoptosis-related diseases such as cancer and neurodegeneration are also covered in this book. While slowly unravelling the complexities of apoptosis in chapter one, the next three chapters individually elaborate on different classes of proteases that play key roles in the initiation, progression and execution of programmed cell death. The last two chapters complete this discussion by describing different laboratory methodologies and therapeutic advances involving apoptotic proteases. Protocols portraying in vitro and ex vivo colorimetric and fluorescence-based enzyme kinetic studies as well as cell death assays are explained in the fifth chapter. Preclinical in vivo models and non-invasive imaging in apoptosis to understand the complexities of disease progression and their contribution toward therapeutics is recounted in the last chapter. The book spans topics related to both fundamental and applied biology. It would therefore be equally appealing and informative to scientists working in the field of apoptosis and those who are investigating mechanisms of proteases and enzymes in general. The protocols would certainly benefit both graduate and undergraduate students working in the related fields and provide useful leads for drug design to translational biologists involved in neurodegeneration and cancer research.

Covers endothelial biology from the fundamentals of structure and lung fluid balance physiology to descriptions of the molecular mechanisms involved in the development of lung failure. This illustrated text provides the knowledge of endothelial function, vascular integrity, pulmonary function, and pathophysiology in respiratory failure.

Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system Features additional coverage throughout and a new volume on toxicology of the hematopoietic system Presents in-depth, comprehensive coverage from an international author base of domain experts