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Pathophysiology of Ischemia-Reperfusion Injury and Use of Fingolimod in Cardioprotection is a deep examination into the mechanisms of myocardial ischemiareperfusion injury and role of fingolimod as a cardioprotective agent through its antioxidant, anti-apoptotic and anti-inflammatory effects. Dr. Ahmed explore the physiology and pathophysiology of myocardial metabolism under normal and ischemic conditions and focused on pharmacological cardioprotection. They provide a concise, yet rigorous discussion of Ischemia-Reperfusion Injury, Myocardial Ischemia during Circulatory Arrest, Myocardial Reperfusion, Myocardial Protection related to Ischemia-Reperfusion Injury and Role of Fingolimod in Cardioprotection.Pathophysiology of Ischemia-Reperfusion Injury and Use of Fingolimod in Cardioprotection is ideal for researchers, cardiovascular scientists, and clinical pharmacologists to further work in this challenging area and apply this knowledge to clinical trials for cardioprotection. - Provides detailed and critical analysis of the latest research in the field from molecular basis to potential clinical relevance - Examines the effect of fingolimod/sphingosine 1-phosphate in cardioprotection, pointing to future myocardial preventative strategies

This book provides new research on immunosuppressives. Chapter One focuses on practical issues concerning immunosuppression in nephrology. Chapter Two discusses the global significance of hepatitis B virus (HBV) infection, the clinical scenarios in which immunosuppresive therapy may reactivate HBV, and different management strategies to prevent HBV reactivation. Chapter Three reviews the effect of immunosuppressive therapy in inflammatory bowel disease (IBD) patients in response to routine vaccinations, and provides a general framework to the approach of vaccinations to these patients.

Personalized Immunosuppression in Transplantation: Role of Biomarker Monitoring and Therapeutic Drug Monitoring provides coverage of the various approaches to monitoring immunosuppressants in transplant patients, including the most recently developed biomarker monitoring methods, pharmacogenomics approaches, and traditional therapeutic drug monitoring. The book is written for pathologists, toxicologists, and transplant surgeons who are involved in the management of transplant patients, offering them in-depth coverage of the management of immunosuppressant therapy in transplant patients with the goal of maximum benefit from drug therapy and minimal risk of drug toxicity. This book also provides practical guidelines for managing immunosuppressant therapy, including the therapeutic ranges of various immunosuppressants, the pitfalls of methodologies used for determination of these immunosuppressants in whole blood or plasma, appropriate pharmacogenomics testing for organ transplant recipients, and when biomarker monitoring could be helpful. - Focuses on the personalized management of immunosuppression therapy in individual transplant patients - Presents information that applies to many areas, including gmass spectrometry, assay design, assay validation, clinical chemistry, and clinical pathology - Provides practical guidelines for the initial selection and subsequent modifications of immunosuppression therapy in individual transplant patients - Reviews the latest research in biomarker monitoring in personalizing immunosuppressant therapy, including potential new markers not currently used, but with great potential for future use - Explains how monitoring graft-derived, circulating, cell free DNA has shown promise in the early detection of transplant injury in liquid biopsy

Organ transplantation has revolutionized the treatment for end-stage organ failure. Immunosuppression is still a major approach currently used in the prevention and treatment of allograft rejection. Both editors Dr. Chen and Dr. Qian have been contributing to preclinical evaluation of immunosuppressants for more than 25 years in North America. Experts from the United States, Canada, the United Kingdom, China, Japan, Germany, Sweden, Hungary and Brazil contributed 23 chapters to this book, providing details of immunological basis in transplantation. They also describe six classes of immunosuppressive agents (calcineurin inhibitors, mTOR inhibitors, JAK-STAT inhibitors, antiproliferative agents, costimulation blockers and corticosteroids), as well as ischemia/reperfusion injury treated agents. Additionally, the new development of cell therapy in the induction of transplant tolerance is introduced. This book provides many important references for the research direction of novel immunosuppressants. Readers that will find this book useful include transplant physicians, surgeons, nurses, immunologists, pharmacologists, pharmacists, medical students, residents and trainees in transplantation.

Streptozotocin (STZ), an antibiotic and anticancer agent, is the most prominent diabetogenic chemical agent in diabetes research due to its cytotoxicity in pancreatic beta-cells. The selective toxicity of STZ due to beta cells occurs because of its preferential accumulation in beta cells through uptake via GLUT2 glucose transporter. Insulin dependent diabetes mellitus can be induced by either single high dose or multiple low- dose STZ injections. At low dose, STZ induces pancreatic beta-cell apoptosis and at high dose it causes necrosis. Though STZ itself can cause carcinogenesis and renal, hepatic and muscle myoblast toxicity, these side effects can be minimized or completely avoided by using lower doses. This book discusses in further detail the different ways in which streptozotocin is used in the medical field.

This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.

There is a great deal of experimental work leading to the conclusion that immuno­ suppression of any kind increases susceptibility to clinical or viral carcinogenesis. Human epidemiology had already given some intimation of the abnormally high incidence of neoplasms in persons suffering from immunologic insufficiency. The first statistics on the incidence of cancer in organ transplant recipients tend to support this thesis. Transplantation can favor metastasis in a recipient who already has a malignancy; similarly, it can encourage the development of tumor cells which may be present in an organ transplanted from a cancerous donor; and finally, the frequency of lymphomas and carcinomas is higher in transplant recipients than in the general population. Immunodepression induced to facilitate tolerance clearly falls under suspicion on the basis of the experimental and clinical findings mentioned above. Anti-lymphocyte serum is not the only suspect-tumors have also occurred in patients treated with prednisone and Imuran alone. Now comes Dr. PENN'S monograph with a detailed account of these phenomena, together with an analysis and discussion. Clearly, induced carcinogenesis in man must be taken seriously. Not only must every precaution be taken in the screening of donor and recipient and the choice of immunosuppressive therapy in order to reduce it to the minimum, there is also the question whether the long-term immunosuppressive treatments inflicted upon patients in whom an auto-immune mechanism is thought to be the cause of the disease-treat­ ments whose efficacy is even more questionable than the mechanism-might not themselves be contributing to malignancy.

This book discusses the mechanisms leading to immune-mediated tissue rejection following the hypothesis that independent of the disease process the final effector mechanism is shared by most (but not all) pathologies and it is relatively simple. The book covers evidence gathered to support the thesis by studies performed in humans during rejection or in experimental models and will focus particularly (but not exclusively) on the analysis of the rejected tissue rather than the systemic circulation. Several disease processes are discussed including example of chronic inflammatory process without resolution of the pathologic process and acute one with resolution of the pathologic process (clearance of pathogen, rejection of tumor) or unwanted tissue destruction (allograft rejection, autoimmunity).

This volume of The Enzymes features high-caliber thematic articles on the topic of glycosylphosphatidylinositol (GPI) anchoring of proteins. - Contributions from leading authorities - Informs and updates on all the latest developments in the field

Cell growth is highly regulated and is controlled by the TOR signaling network. Dysfunction of signaling pathways controlling cell growth results in cells of altered sizes and in turn causes developmental errors and a wide range of pathological conditions. An understanding of the TOR signaling network may lead to novel drugs for the treatment of, for example, cancer, diabetes, inflammation, muscle atrophy, learning disabilities, depression, obesity and aging. There has been an explosion of knowledge in this area in recent years and this volume provides an in-depth review of our current knowledge of TOR complexes by the leaders in the field. - Contributions from leading authorities - Informs and updates on all the latest developments in the field

Chronic graft versus host disease (GVHD) is the most common complication of allogenic bone marrow transplantation. Because of the protracted clinical course of chronic GVHD, transplant centers and hematology/oncology offices are inadequately equipped to manage these immuno-incompetent patients with a multi-system disorder. Practitioners need to be able to recognize and effectively manage chronic GVHD as a late effect of more than half of allogenic transplantations. The text is oriented for the clinician, with chapters covering staging, organ site and system-specific manifestations, treatment options, and supportive care. Drs Georgia B. Vogelsang and Steven Z. Pavletic have been pioneers in the recognition of the multi-organ complexity of this disease and have gathered the input of a variety of subspecialist physicians for this book. This book fills the gap in practical literature on chronic GVHD, providing a comprehensive, up-to-date, and clinically relevant resource for anyone who deals with cancer patients post-transplant.

Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. Deliberately induced immunosuppression is generally done to prevent the body from rejecting an organ transplant, treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases such as rheumatoid arthritis or Crohn's disease. This is typically done using drugs, but may involve surgery (splenectomy), plasmapharesis, or radiation. A person who is undergoing immunosuppression, or whose immune system is weak for other reasons (for example, chemotherapy and HIV patients) is said to be immunocompromised. When an organ is transplanted, the immune system of the recipient will most likely recognize it as foreign tissue and attack it. The destruction of the organ will, if untreated, end in the death of the recipient. In the past, radiation therapy was used to decrease the strength of the immune system, but now immunosuppressant drugs are used to inhibit the reaction of the immune system. The downside is that with such a deactivated immune system, the body is very vulnerable to opportunistic infections, even those usually considered harmless. Also, prolonged use of immunosuppressants increases the risk of cancer. This new book presents the latest research in the field.

This book discusses the immunobiology of Cytotoxic T lymphocyte antigen 4. It is one of the first wide-ranging attempts to conceive the role of molecules outside the major histocompatibility complex region as a common denominator for autoimmune diseases.

In recent years there has been a growing recognition that such widely used immunosuppressant drugs as cyclosporin and FK-506 and their analogs-the neuroimmunophilins-possess significant neurotrophic and neuroprotective properties in addition to their beneficial effects for transplant patients. In Immunosuppressant Analogs in Neuroprotection, pioneers in the field and leading neuroscientists and clinicians working with these drugs survey the most recent scientific evidence showing how they evolved from being purely immunosuppressant'drugs'to neuroprotective'agents.'These authorities focus on recent preclinical evidence that demonstrates the neurotrophic/neuroprotective effects of immunosuppressants when administered alone or when combined with neural transplantation therapy in animal models of neurological disorders. They discuss their efficacy and mechanisms of action in vitro and in vivo; using these models of CNS disease, they report laboratory studies with compelling clinical indications for Alzheimer's disease, Huntington's disease, stroke, traumatic brain injury, spinal cord injury, ALS, sciatic nerve injury, and drug addiction. They also present novel hypotheses on the mechanisms of neuroprotection, ranging from the blockade of mitochondrial permeability transition pores to free radical scavenging to the inhibition of calcineurin. Authoritative and cutting-edge, Immunosuppressant Analogs in Neuroprotection demonstrates that CsA, FK-506, and the immunophilins exert neuroprotective effects on their own and will serve well as a new breed of neuroprotective agents for the treatment of neurological disorders.

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

Novel molecular motifs named Immunoreceptor Tyrosine-based Inhibition Motifs (ITIMs) have recently been recognized in the intracytoplasmic domains of a still-increasing number of receptors which control cell activation and proliferation. Research on ITIM-bearing molecules has developed exponentially during the last three years, generating new concepts with important consequences in basic research and with exciting potential clinical applications. The present volume contains 15 reviews written by authors who all made significant contributions to the identification of ITIM-bearing molecules and the study of their biological properties. It constitutes the first synthesis ever published that is specifically devoted to this emerging topic.

Immunity, Cancer, and Chemotherapy focuses on the interference of drugs on antibody response and transplantation immunity. The selection first offers information on the effects of immunosuppressive drugs on cellular changes after antigenic stimulation and specialized cell function in the lymphoid and reticuloendothelial cell series. Topics include effects of immunosuppressive drugs on the sensitization process; cellular changes in lymphoid tissue following sensitization; and demonstration of differences in antigen handling among cells of the reticuloendothelial system. The text also takes a look at allogeneic inhibition and its possible relation to cell-bound immunity in vitro and the effects of immunosuppressive drugs at various stages of differentiation of immunologically competent cells. The publication examines a study of antibody-containing cells in the course of immunization and cellular differentiation during immune responses studied with electron microscope and radioautography. The text also elaborates on ambiguity in the translation of genetic code into proteins, induced by aminoglycoside antibiotics and immunosuppressive agents and cellular kinetics of immune response. The selection is a dependable source of information for readers interested in effects of drugs on antibody response and transplantation immunity.