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The World Stroke Organization reports that “stroke has already reached epidemic proportions. Globally1 in 4 adults over the age of 25 will have a stroke in their lifetime. 12.2 million people worldwide will have their first stroke this year, and 6.5 million will die as a result.” Ischemic strokes are the most common type of stroke, with about 87% of all strokes being ischemic strokes.This new volume addresses this epidemic by presenting detailed studies on ischemic injury, with emphasis on the molecular-level mechanisms and the role of signaling pathways in the body, their structure, and their mechanism of action. The book focuses on molecular pharmacology plans and explains the new areas of research on the discovery of therapeutic molecules that can be used for combating this life-threatening disease. The authors discuss stroke occurrence at different stages of life as well as sex-based differences in its treatment. They cover aspects of the clinical treatment and diagnosis of patients with cardiovascular events, including in-depth information on the prevention, evaluation, therapy selection, result projection, and long-term course of the disease in affected patients. They also detail the involvement of platelets, neurotransmitters, renin-angiotensin-aldosterone system, and vitamin D in ischemic injury.

This book provides a comprehensive overview of plants and plant-derived phytochemicals in the management of cardiovascular diseases. It presents the cardioprotective potential of plants and phytochemicals, covering various preclinical models, assays, and clinical research protocols of plant medicine for cardioprotection. Chapters cover the role of plants and phytochemicals in prevention and cure of atherosclerosis, hypertension, cardiomyopathy, arrhythmia, myocardial ischemia, cardiotoxicity and the underlying pharmacological, molecular, biochemical, and immunobiological mechanisms. The book also includes toxicological aspects (safety evaluations), meta-analysis of clinical trials, critical assessments, drawbacks and challenges for adopting phytomedical approaches in evidence-based medicine for the treatment of CVDs. Screening methods and plant foods for cardioprotection are also covered. The book will be a reference for all researchers working on the role of plant-based products on cardiovascular systems and on cardioprotective agents of plant origin. It will be useful for students, researchers, physicians, nurses, industrial scientists, nutritionists, pharmacists, pharmacologists, toxicologists, botanists, and traditional medicine practitioners. In particular, researchers working on heart problems, diseases, toxicity, physicians treating patients with heart problems, hospitals, pharmacy institutions, pharmacy students and researchers, ethnobotanists, and people working in traditional medicine will find this book useful.

Taurine, or 2-aminoethanesulfonic acid, is one of the most abundant sulfur-containing amino acids in the human body. It is found in the heart, brain, retina, and skeletal muscles, and is synthesized in the pancreas. Studies have revealed that taurine is of high physiological importance: it protects against pathologies associated with mitochondrial diseases, and linked processes like aging, metabolic syndrome, cancer, cardiovascular diseases, and neurological disorders. It is also used as a nutritional supplement. Taurine and the Mitochondrion: Applications in the Pharmacotherapy of Human Diseases explores the significance of taurine in the biology of mitochondria. It also explains its role as a pharmacological agent for treating different diseases. Readers will gain an insight into the crucial role it plays in human physiology and the benefits of taurine supplements.Topics covered in this reference include- Synthesis of taurine and its dietary sources- The Role of taurine in mitochondrial health- Taurine as a neurotransmitter- Beneficial effects of taurine in physiological systems such as the reproductive system, renal system, and the gastrointestinal tract- Hepatoprotective and anti-inflammatory properties of taurine- The anti-aging promise of taurine supplementation- Role of taurine supplementation in obesity

Modulation of Oxidative Stress: Biochemical, Physiological and Pharmacological Aspects explores the field using an interdisciplinary approach, including chemical, biological, physiological, pharmaceutical, pharmacological and physicochemical perspectives. The book is comprised of three main parts, with the first discussing the biochemical aspects of oxidative stress modulation. Other sections cover physiological and pathophysiological aspects on relevant conditions, including aging, neurological diseases, cerebral cavernous malformation, maternal and early-life malnutrition, Alzheimer's disease, liver transplant, and cancer. Final content is dedicated to pharmacological aspects and includes chapters on phytotherapy and flavonoids. This book is a strong reference for pharma researchers in academia and industry considering leveraging modulation of oxidative stress as a strategy for the development of new drugs. Biochemists and Nutritionists may also benefit of the foundational understanding of cellular redox processes laid out. - Provides the latest updates in the fast-developing field of REDOX biochemistry and pharmacology - Presents content that is clear and easy to read - Useful for researchers and instructors in many fields

Medicinal Chemistry of Chemotherapeutic Agents: A Comprehensive Resource of Anti-infective and Anti-cancer Drugs focuses on the basics and fundamentals of chemistry involved in chemotherapeutic agents. Each chapter comprises distinct chemical classifications that include structure and IUPAC nomenclature, synthetic schemes and routes for each drug, mechanism of the drug action, metabolic pathway and structure–activity relationship (SAR) studies. The book covers current research focused on drug resistance and methods to overcome it, the development of newer drugs belonging to each category of the chemotherapeutic agents, molecules currently under clinical trials, and newly approved drugs, if any. This book will be a valuable resource for academics and researchers, helping them to understand the fundamentals of the medicinal chemistry of the chemotherapeutic agents. - Includes current research focused on drug resistance and methods to overcome problems - Outlines synthetic schemes and metabolic pathways of chemotherapeutic agents - Discusses molecules under clinical trials and newly approved drugs

Interest in RNA nanotechnology has increased in recent years as recognition of its potential for applications in nanomedicine has grown. Edited by the world's foremost experts in nanomedicine, this comprehensive, state-of-the-art reference details the latest research developments and challenges in the biophysical and single molecule approaches in RNA nanotechnology. In addition, the text also provides in-depth discussions of RNA structure for nanoparticle construction, RNA computation and modeling, single molecule imaging of RNA, RNA nanoparticle assembly, RNA nanoparticles in therapeutics, immunorecognition of RNA nanomaterials, RNA chemistry for nanoparticle synthesis, and conjugation and labeling. Presents the latest research and discoveries in RNA nanotechnology Features contributions from world-class experts in the field Covers RNA nanoparticles in therapeutics Describes self-assembled RNA nanoparticles

Hydrogen sulfide (H2S) has emerged as an important gas signalling molecule in a series of organs/tissues, on the diseases of which it plays protective roles, such as proangiogenic effects in ischemic tissues, antiapoptotic effects in the cardiomyocytes, regularization of fatal arrhythmia in myocardial infarction, amelioration of inflammation in autoimmune diseases, modification of neuronal transmission, increase in sodium excretion from the kidney, and amelioration of insulin resistance, etc. This book focuses on the effect of hydrogen sulfide in cardiovascular system, immune system, nervous system, kidney, as well as on the metabolism of glucose and lipids and regulation of ion channels and so on. This book also provides the advances in the understanding of endogenous H2S metabolism and H2S protein targets, as well as H2S donors. It will benefit researchers in both academics and industry working on the underlying mechanism of H2S field and the future of translational medicine of H2S.

Systemic Drug Delivery Strategies: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy, Volume 2 examines the challenges of delivering immuno-oncology therapies, focusing specifically on the multiple technologies of affective drug delivery strategies. Immuno-oncology (IO) is a growing field of medicine at the interface of immunology and cancer biology leading to development of novel therapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) and immune checkpoint blockade antibodies, that are clinically approved approaches for cancer therapy. Although currently approved IO approaches have shown tremendous promise for select types of cancers, broad application of IO strategies could even further improve the clinical success, especially for diseases such as pancreatic cancer, brain tumors where the success of IO so far has been limited. This volume of Delivery Strategies and Engineering Technologies in Cancer Immunotherapy discusses methods of targeting tumors, CRISPR technology, and vaccine delivery among many other delivery strategies. Systemic Drug Delivery Strategies: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy, Volume 2 creates a comprehensive treaty that engages the scientific and medical community who are involved in the challenges of immunology, cancer biology, and therapeutics with possible solutions from the nanotechnology and drug delivery side. - Comprehensive treaty covering all aspects of immuno-oncology (IO) - Novel strategies for delivery of IO therapeutics and vaccines - Forecasting on the future of nanotechnology and drug delivery for IO

Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.

The aim of this book is not only to introduce readers with a broad spectrum of biological actions of the NOP receptor, but also to feature a detailed look at the N/OFQ-NOP receptor system, medicinal chemistry, pharmacology, and clinical data of NOP-targeted ligands. This special volume book - for the first time focusing on the NOP receptor - is designed to serve as a useful reference, stimulate more research on the N/OFQ-NOP receptor system, and lead to more development of NOP-related ligands for several therapeutic applications.

This timely book reveals an integrated approach to myocardial preservation focusing on translational research and clinical applications. Chapters cover both the mechanisms of heart failure in addition to therapeutic considerations, including forms of cardiac cell death, cardiac remodelling and cardiac regeneration. Potential future research directions are also proposed, enabling the reader to gain a broad in-depth understanding of the topic.Myocardial Preservation: Translational Research and Clinical Application presents a thorough review of myocardial preservation. Its comprehensive approach provides a valuable reference for cardiology researchers and practising and trainee cardiologists seeking new insight to the topic.

In this book, a summary and update of the most important areas of cell-penetrating peptides (CPP) research are presented, while raising relevant questions for further development. The CPP sequences are presented and discussed throughout the book. The methods for testing CPP mechanisms are discussed in detail. Various approaches for the testing of endocytotic pathways of CPP uptake are also described. Different CPP uptake experiments are compared since it is becoming clear that it is often best to apply several methods in a complementary manner in order to most comprehensively evaluate CPP uptake mechanisms due to the complexity of these processes. A brief summary of functionality issues of CPPs, both in vitro and in vivo, is discussed. Therapeutic potential of CPPs and commercial developments are discussed. The present, second edition of this book is the updated and expanded version of the first edition, published in 2019. The development of the field of cell-penetrating peptides in these five years has been obvious and exciting. This second edition of the book has been partly reorganized and comprehensively expanded with the exciting research in 2019-2023. Around 2500 novel scientific articles have become available, most of them are reviewed in the second edition. Additional rapidly growing areas of high impact presented in this second edition are therapeutic developments (Chapter 16) and delivery of oligonucleotides and proteins/peptides (Chapters 5 and 6) including novel reports on genome editing with CPP assistance. Also, several additional examples are available now on clinical trials using CPPs (Chapter 15). The book is written for researchers and students in the field.

Glutathione (GSH) is a ubiquitous tripeptide (γ-L-glutamyl-L-cysteinyl-glycin) playing an important role in cellular redox homeostasis, defense against electrophilic reactive species, and control of several cellular events, among others. Most of these cellular functions are related to its thiol (SH) function of the cysteine moiety. With increasing knowledge on the molecular basis of its cellular functions, use of GSH as a nutritional supplement is receiving increasing interest. The present book summarizes the recent literature and new developments on three distinct, but closely related topics: Production, biochemical functions, implications and applications of glutathione. The topics cover comprehensive reviews on physico-chemical characterization, pharmacopoeial qualification, biotechnological production, surveys on different analytical methods for its quantitation, and the role of several physiological abnormalities (e.g., cardiac diysfunctions, neurological disorders, kidney injuries and different types of cancer) related to non-appropriate biosynthesis and/or metabolism of endogenous GSH. The information presented represents a valuable source for advanced students, scholars, teachers and scientists (academic and industrial) interested or already engaged in research that involves glutathione.

Frontiers in Cardiovascular Drug Discovery is an eBook series devoted to publishing the latest advances in cardiovascular drug design and discovery. Each volume brings reviews on the biochemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships of molecules used in cardiovascular therapy. The eBook series should prove to be of great interest to all medicinal chemists and pharmaceutical scientists involved in preclinical and clinical research in cardiology. The fourth volume of the series covers the following topics: -Aspirin administration -Adenosine receptor targeting for cardiovascular therapy -Drug treatment of patients with coronary stenting -Immunosuppressive drugs in heart transplantation -PCSK9 inhibition for lowering LDL-C levels.

This extensive volume began as a short course primarily geared toward toxicologists who want to expand their understanding of toxicologic pathology in order to be better study directors while also proving to be of great interest to other drug development scientists and regulatory reviewers. The overall goal is to help non-pathologists understand, contextualize, and communicate the pathology data and interpretations from the study pathologist in a practical and usable format. Within the book, readers will find an overview of general pathology concepts that include fundamental vocabulary and the basics of pathophysiological processes, along with numerous chapters devoted to pathology in specific organ systems as well as topics such as biomarkers, correlation of clinical pathology endpoints (chemistry and hematology) with microscopic changes, and well-known pathology findings for classes of toxic substances. Authoritative, practical, and comprehensive, Toxicologic Pathology for Non-Pathologists aims to help non-pathologists understand, converse in, and apply a basic understanding of pathology in their day-to-day careers.

Leading researchers are specially invited to provide a complete understanding of a key topic within the multidisciplinary fields of physiology, biochemistry and pharmacology. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

This book addresses the therapeutic strategies to target mitochondrial metabolism in diseases where the function of that organelle is compromised, and it discusses the effective strategies used to create mitochondrial-targeted agents that can become commercially available drug delivery platforms. The consistent growth of research focused in understanding the multifaceted role of mitochondria in cellular metabolism, controlling pathways related with cell death, and ionic/redox regulation has extended the research of mitochondrial chemical-biological interactions to include various pharmacological and toxicological applications. Not only does the book extensively cover basic mitochondrial physiology, but it also links the molecular interactions within these pathways to a variety of diseases. It is one of the first books to combine state-of-the-art reviews regarding basic mitochondrial biology, the role of mitochondrial alterations in different diseases, and the importance of that organelle as a target for pharmacological and non-pharmacological interventions to improve human health. The different chapters highlight the chemical-biological linkages of the mitochondria in context with drug development and clinical applications.

This volume describes our current understanding of the biological role of the delta-opioid receptor (DOR) system, focusing on its unique mechanisms of receptor trafficking and signaling in disease states. Part 1 covers the endogenous ligands that regulate the DOR system as well as novel compounds and therapies used to modulate the DOR system. Part 2 describes new insights into the localization and trafficking of the DOR and how ligand-directed signaling alters the fate of the receptor. Part 3 concentrates on the potential role of the DOR system in disease states, such as pain, mood, addiction, and Parkinson's disease. Throughout the book, the DOR system as a target for drug development will be discussed.

Following the success of the first edition, this book is designed to provide practical and timely information for toxicologic pathologists working in pharmaceutical drug discovery and development. The majority of the book (Organ Systems) will provide detailed descriptions of histopathological lesions observed in drug development. In addition, it will provide information to assist the pathologist in making determinations of the origin of lesions as well as its relevance to human risk.Toxicologic Pathology: Nonclinical Safety Assessment, Second Edition includes 2 new concept chapters. The first of the new chapters address approaches for the evaluation of unique therapeutic modalities such as cell therapies, gene therapies, and gene expression knockdown therapies. While these still represent new developing therapeutic approaches, there has been significant experience with the therapeutic modalities in the last 5 years. The second new chapter addresses the nonclinical safety assessment of medical devices, a topic of increasing importance that was not addressed in a unique chapter in the first edition. The other concept chapters have been updated and cover important topics including the overview of drug development; principles of nonclinical safety assessment; an introduction to toxicologic pathology; techniques used in toxicologic pathology, clinical pathology, toxicokinetics, and drug development toxicogenomics; and spontaneous lesions. The 13 organ system chapters provide the specifics related to pathologic characteristics, differential diagnosis, and interpretation of toxic responses in each organ system. These chapters are specifically important for the bench pathologist but also for the toxicologist who interacts with pathologists and function as study toxicologists and project team representatives in the drug development arena.

Continuing a long tradition, Lu‘s Basic Toxicology, Seventh Edition, provides guidance on principles of toxicology and testing procedures for toxicities as well as a concise yet detailed mechanism of both target organ and non-target organ toxicities. The book also addresses the toxic effects of chemicals and risk assessment, giving students and practicing toxicologists, the tools to enhance their practice. This edition includes new chapters on Systems Toxicology, Chemicals and Children, Toxicology of Reproductive Systems, providing the essentials of these topics in the same style as other chapters in the book. Separate subject and chemical indexes make this a useful, quick shelf reference.

Nitric Oxide Donors: Biomedical Applications and Perspectives presents the current state of art, challenges and innovations in the design of therapeutics nitric oxide donors with great impact in several aspects of human physiology and pathophysiology. Although considerable innovative progress has been achieved using Nitric Oxide donors in biomedical applications, certain drawbacks still need to be overcome to successfully translate these research innovations into clinical applications. This book encompasses several topics on nitric oxide such as its sources and biological properties; its performance in the cardiovascular and neurologic systems, in the human skin and its application in the treatment of neglected diseases, neurodegenerative disorders, and cancer. Additionally, it covers its role in inflammation and immunity, penile erection function, photodynamic therapy, antimicrobial activities. It also discusses the future of nitric oxide donors in combination with other therapeutic drugs, in implantable sensors, and nitric oxide releasing hydrogels and medical devices for topical applications. The book is a valuable source for researchers on different areas of biomedical field who are interested in the improvements that these molecules can make in the treatment of several conditions. - Provides background information about biology and chemistry of nitric oxide - Discusses the state-of-the-art in the design of nitric oxide releasing nanomaterials for biomedical applications - Covers the usage of nitric oxide donors in the treatment of several conditions, such as cancer, human skin, cardiovascular system, and immunity - Discusses the future of nitric oxide donors and their FDA approval

At a time when the field of cardiac safety is going through important changes, this unique book provides the rationale for, and cutting-edge explanations of, new regulatory landscapes that will likely govern cardiac safety assessments globally for the foreseeable future. Exposure-response modeling is already being accepted by regulatory agencies in lieu of the traditional Thorough QT/QTc Study, and the Comprehensive in vitro Proarrhythmia Assay initiative is well under way. Developments in the field of cardiovascular safety are also described and discussed in the book. These include the search for more efficient ways to exonerate new drugs for type 2 diabetes from an unacceptable cardiovascular liability, how best to address off-target blood pressure increases induced by noncardiovascular drugs, and the continued evolution of the discipline of Cardio-oncology.“a resource that will likely serve as a standard for years to come” - Dr Jonathan SeltzerTherapeutic Innovation & Regulatory Science, 2017;51(2):180“I have no hesitation in recommending this book as a valuable reference source” - Dr Rashmi ShahJournal for Clinical Studies, 2017;9(1):62-63

The present book covers the basic principles of cardiovascular physiology, pathophysiology and advanced pharmacology with particular emphasis on cellular mechanisms of drug action. It provides an update on the progress made in several aspects of cardiovascular diseases so that it might kindle scientists and clinicians alike in furthering basic and translational research. In addition, the book is expected to fill imperative gaps in understanding and optimally treating cardiovascular disease.

In this second edition of Post-Genomic Cardiology, developing and new technologies such as translational genomics, next generation sequencing (NGS), bioinformatics, and systems biology in molecular cardiology are assessed in light of their therapeutic potential. As new methods of mutation screening emerge, both for the genome and for the'epigenome, comprehensive understanding of the many mutations that underlie cardiovascular diseases and adverse drug reactions is within our reach. This book, written by respected cardiologist José Marín-García, features discussion on the Hap-Map: the largest international effort to date aiming to define the differences between our individual genomes. This unique reference further reviews and investigates genome sequences from our evolutionary relatives that could help us decipher the signals of genes, and offers a comprehensive and critical evaluation of regulatory elements from the complicated network of the background DNA. - Offers updated discussion of cutting-edge molecular techniques including new genomic sequencing / NGS / Hap-Map / bioinformatics / systems biology approaches - Analyzes mitochondria dynamics and their role in cardiac dysfunction, up-to-date analysis of cardio-protection, and cardio-metabolic syndrome - Presents recent translational studies, gene therapy, transplantation of stem cells, and pharmacological treatments in CVDs

Cellular and Molecular Pathobiology of Cardiovascular Disease focuses on the pathophysiology of common cardiovascular disease in the context of its underlying mechanisms and molecular biology. This book has been developed from the editors'experiences teaching an advanced cardiovascular pathology course for PhD trainees in the biomedical sciences, and trainees in cardiology, pathology, public health, and veterinary medicine. No other single text-reference combines clinical cardiology and cardiovascular pathology with enough molecular content for graduate students in both biomedical research and clinical departments. The text is complemented and supported by a rich variety of photomicrographs, diagrams of molecular relationships, and tables. It is uniquely useful to a wide audience of graduate students and post-doctoral fellows in areas from pathology to physiology, genetics, pharmacology, and more, as well as medical residents in pathology, laboratory medicine, internal medicine, cardiovascular surgery, and cardiology. - Explains how to identify cardiovascular pathologies and compare with normal physiology to aid research - Gives concise explanations of key issues and background reading suggestions - Covers molecular bases of diseases for better understanding of molecular events that precede or accompany the development of pathology

​In this fast moving field the main goal of this volume is to provide up-to-date information on the molecular and functional properties and pharmacology of mammalian TRP channels. Leading experts in the field describe properties of a single TRP protein/channel or portray more general principles of TRP function and important pathological situations linked to mutations of TRP genes or their altered expression. Thereby this volume on Transient Receptor Potential (TRP) Channels provides valuable information for readers with different expectations and backgrounds, for those who are approaching this field of research as well as for those wanting to make a trip to TRPs.

As drug development shifts over time to address unmet medical needs and more targeted therapies are developed, previously unseen pharmacological or off-target effects may occur in treatment. Designed to provide practical information for the bench toxicologic pathologist working in pharmaceutical drug research, Toxicologic Pathology: Nonclinical Saf

This work is concerned with a group of proteins which were originally consid­ ered to be an esoteric phenomenon but which have now been shown to play critical roles both in normal and stressed cells as well as being involved in a variety of human diseases. It is the purpose of this work to give a comprehen­ sive view of these proteins and their various aspects. After an introductory chapter providing an overview of these proteins, the work is divided into four main sections each of which deals with one important aspect of these proteins. Thus, the first section contains a series of chapters which describe individual stress proteins and their roles in particular biological phenomena. Evidently, the induction of these proteins by elevated tempera­ ture or other stresses is their defining feature and the second section of this book therefore considers the regulation of stress protein gene expression both by stressful stimuli such as elevated temperature or ischaemia and by non­ stressful stimuli such as cytokines.

A decade ago, for most scientists investigating various issues in life sciences the word'NO'was used in a negative context. It is astounding to observe how recently researchers are addressing the issue of NO, namely, nitric oxide, in over fifty publications weekly. Science journal, while naming nitric oxide:'Molecule of the Year'(December 1992), said it all:'NO news is good news.'For a long period of time NO was considered as a pollutant and every ecology­ minded person tried to eliminate it. It was the discovery of NO involvement in the process of host killing by macrophages and several years later the finding that EDRF is none else but NO, that promoted this field. Nitric oxide's major role in the control of blood pressure is merely one factor of an extensive list of effects and functions attributed to it. NO is implicated in long-term potentiation (LPT), a principal process involved in memory consolidation and it is considered as the main biochemical substance responsible for penile erection. It should be noted that additional roles for NO are discovered continuously as many laboratories join the quest for the mystery of this small molecule. The observation that NO is involved in various biological processes is not unique, as other second messengers (i. e., cyclic AMP), participate in a diverse set of functions.

Chronic exposure to environmental toxigenic molds mycotoxins, especially in water-damaged buildings is an indoor environmental health problem to which escalating health and property insurance costs are raising concerns in recent times. Hence, controversies exist, some of which are based on misunderstanding and economic motives. Nevertheless, it must be stated that molds and fungi in general have both pharmaceutical desired and toxicological undesired effects on human and animal environmental health. However, a lack of sufficient scientific interest and recognition shroud the status of molds and fungi as the most important and oldest known component of human adaptive flora to which nature provides human survival with all the basic ingredients to defend them against undesired microbial pathogenic attacks. However, because these adaptive provisions are common, they are casually neglected from serious interests in terms of vigorous research values and exploitation for human benefits. Consequently, the unraveling of the myth surrounding the complex functional ambivalence of toxigenic molds and mycotoxins may after all hold the key to human infectious disease control. This book is unique in the sense that it assumes a pioneering position based mainly on published work in peer-reviewed literature and it integrates all the facets of evidence based clinical environmental mycopathology with basic analytic laboratory scientific findings. It highlights the importance of the environmental health effects of toxigenic molds and mycotoxins and the need for further development of knowledge in this area through transnational clinical an basic science research. The overall organization of this book reflects the author's many years of research, teaching and published work in clinical neurophysiology and environmental mycotoxicology.

“Frontiers in Medicinal Chemistry” is an Ebook series devoted to the review of areas of important topical interest to medicinal chemists and others in allied disciplines. “Frontiers in Medicinal Chemistry” covers all the areas of medicinal chemistry, including developments in rational drug design, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, chemoinformatics, and structure-activity relationships. Medicinal chemistry as a discipline is rapidly maturing. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. “Frontiers in Medicinal Chemistry” aims to contribute in a major way to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. This Ebook series is essential for any medicinal chemist who wishes to be kept informed and up-to-date with the latest and the most important advances.

Considerable progress has been made in our healthcare system, in particular with respect to sensitive diagnostic tools, reagents and very effective and precise drugs. On the other hand, high-throughput screening technology can screen vast numbers of compounds against an array of targets in a very short time, and leads thus - tained can be further explored. In developing countries, the exploding population exerts pressure not only on natural resources but also on the human population - self, whose members strive to become successful and advance in society. This leads to increased blood pressure, anxiety, obesity-associated lipid disorders, cardiov- cular diseases and diabetes. Most of these diseases result in disturbed family life, including sexual behaviour. Despite technological developments, herbal drugs still occupy a preferential place in a majority of the population in the Third World and terminal patients in the West. Herbal drugs, in addition to being cost effective and easily accessible, have been used since time immemorial and have passed the test of time without having any side effects. The multitarget effects of herbs (holistic approaches) are the fun- mental basis of their utilization. This approach is already used in traditional systems of medicine like Ayurveda, which has become more popular in the West in recent years. However, the integration of modern science with traditional uses of herbal drugs is of the utmost importance if ones wishes to use ancient knowledge for the betterment of humanity.

Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular basis of drug action, both applied and experimental. - Articles written by leading investigators in the field - Informs and updates on all the latest developments

After the discovery of endogenous NO formation in the late'80s and the 1998 Nobel Prize in Physiology or Medicine, many researchers and physicians again became interested in the NO/sGC interaction and cGMP-dependent signaling. This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. Particular attention will also be given to clinical applications of the novel cGMP-elevating drugs which are on the horizon, thus spanning the continuum from basic science to clinic.

Oxidants, like other aspects of life, involves tradeoffs. Oxidants, whether intentionally produced or by-products of normal metabolism can either mediate a variety of critical biological processes but when present inappropriately cause extensive damage to biological molecules (DNA, proteins, and lipids). These effects can lead to either damage that is a major contributor to aging and degenerative diseases (or to other diseases such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts) or normal physiological function- tissue repair, defense against pathogens and cellular proliferation. On the other hand the body is equipped with a complex antioxidant/oxidant handling system which includes both enzymatic and nonenzymatic (i.e. small molecules such as flavonoids, ascorbate, tocopherol, and carotenoids) produced endogenously or derived from the diet. This book focuses on how the same molecules can have favorable or noxious effects depending on location, level and timing. Each chapter focuses on one particular molecule or oxidant/antioxidant system and provides a state of the art review of the current understanding regarding both positive and negative actions of the system under review.

With the prevalence of neurodegenerative diseases on the rise as average life expectancy increases, the hunt for effective treatments and preventive measures for these disorders is a pressing challenge. Neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis have been termed ‘protein misfolding disorders'that are char- terized by the neural accumulation of protein aggregates. Manipulation of the cellular stress response involving the induction of heat shock proteins offers a the- peutic strategy to counter conformational changes in neural proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Heat shock proteins are protein repair agents that provide a line of defense against misfolded, aggregati- prone proteins. Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection reviews current progress on neural heat shock proteins (HSP) in relation to neurodegenerative diseases (Part I), neuroprotection (Part II), ext- cellular HSP (Part III) and aging and control of life span (Part IV). Key basic and clinical research laboratories from major universities and hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for researchers, postdoctoral fellows and graduate students in the fields of Neuroscience, Neurodegenerative Diseases, Molecular Medicine, Aging, Physiology, Pharmacology and Pathology.

Covers the major drug categories that are relevant to rehabilitation specialists, focusing on drug indications, mechanism of action, and impact on rehabilitation.

The perceived lack of drug discovery productivity in recent times has led to much debate in the pharmaceutical/biotechnology industry as escalating R&D costs are not being matched by increased output. Few observers doubt that selecting the right targets, ie those which are critical to disease pathology and are'druggable', is the best starting point for improved productivity.The seven chapters of this volume describe recent progress towards drugs acting at a range of'druggable'targets. One chapter addresses kinases, one covers an ion channel, two proteases are featured and three of the chapters cover G-protein coupled receptors, which has historically perhaps been the most fruitful area for medicinal chemists.•Presents the latest research in the field of drug discovery •Publishes on an annual basis to bring you the most innovative updates in medicinal chemistry •Available as an online resource via ScienceDirect

As a result of domestication - considered to be the most important cultural development of the past 13,000 years of human history - we depend today on a tiny number of domesticated plant and animal species for our food supply. Nevertheless, people continue to gather food which grows around their homes or they cultivate local varieties of food plants (as well as keep land races of domestic animals). Generally, wild varieties tend to be richer in micronutrients and bioactive secondary metabolites, which are produced in adaptation to local environmental conditions. These metabolites trigger further adaptive responses by producing ‘protective', bioactive compounds which, when ingested, result in the transfer of protective effects to our organism. The preservation of local knowledge for future generations as well as the identification of new nutraceuticals by means of characterizing plant extracts with potential health beneficial effects are the main objectives of this book. The first part therefore focuses on the ethnobotanical study of local food plants in selected regions of the Mediterranean, i.e. their use as well as beliefs and cultural practices associated with it. The biological-pharmacological effects of these plants on selected (mostly in vitro) targets of the central nervous system and the cardiovascular system make up the second part, highlighting the potential of these plants for developing novel health foods, herbal medicines or local products with beneficial effects on health. Those interested in an integrated approach to the identification of new and health beneficial foods will undoubtedly find this book a valuable source of information and an inspiration for new scientific approaches to this age-old topic.

The revolution in molecular medicine makes it imperative to integrate the classical and molecular approaches to drug development for the treatment of heart disease, the number one killer in North America and Europe. In the Cardiac Drug Development Guide, basic medical researchers, clinicians, and pharmacologists join forces to comprehensively survey the most recent breakthroughs in molecular cardiology and review the latest drug discoveries in cardiac and cardiovascular medicine. Topics range from novel molecular targets for cardiac drug development, to functional endpoints for evaluating cardiac drug activity, to clinical aspects of cardiovascular therapeutics. The authors describe the most advanced procedures in cardiovascular pharmacology, including in vivo and in vitro whole animal studies, the electrophysiological methods used to study pacemaker cells, and the application of biochemical principles and technologies to novel therapeutic agents. Also discussed are the methods used to express the ion channels involved in cardiovascular pharmacology, adenoviral vector delivery for cardiovascular gene therapy, pharmacometrics in cardiovascular drug development, gender differences in heart failure, and angiogenesis therapies for coronary heart disease. Each chapter concisely illustrates the concepts described and includes comprehensive background information, detailed figures and tables, and an up-to-date list of the most important references. Comprehensive and easy-to-understand, the Cardiac Drug Development Guide offers pharmacologists, cardiologists, and physiologists not only a gold-standard survey of the many different methods being used to develop new heart drugs, but also details powerful new ways in which cardiovascular disease is targeted, from the whole organ to the genetic level.

Knowledge of the basic mechanisms of human disease is essential for any student or professional engaged in drug research and development. Functional gene analysis (genomics), protein analysis (proteomics), and other molecular biological techniques have made it possible to understand these cellular processes, opening up exciting opportunities for no

Poly (ADP-ribose) polymerase (PARP), also termed poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme with a wide range of functions, including regulation of DNA repair, cell differentiation, and gene expression. More than a decade after the identification of PARP-like enzymatic activities in mammalian cells, a novel role was proposed for this e