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This book goes in depth about the lymphatic system and the functions of the lymphatic organs, lymphatic tissues, and lymphatic vessels. The book addresses various types of diseases in which the lymphatic system can act as a targeting site for drug absorption and suggests strategies to treat these different infections of the lymphatic system. This book is intended for academicians who work in fields related to the lymphatic system, novel drug delivery systems, pharmaceutical science, novel-material sciences, as well as professionals in the medical, nursing, or other health care industries.

The book delves into various aspects of the hair care industry, providing a comprehensive understanding of hair throughout history, its anatomy and physiology, genetics and molecular mechanisms of hair color, and the raw materials used in the industry. It explores the diverse range of hair care products, including oils, dyes, lotions, and serums, and emphasizes the importance of global regulatory approaches to ensure consumer health and safety, particularly in relation to nano-formulations and synthetic hair care products. The book also addresses the safety and efficacy of herbal care products from a global regulatory perspective. Furthermore, it examines the impact of the microbiome on hair care products, highlighting the opportunities and challenges in complying with global regulations. The evaluation of hair care product safety is discussed within a global context, exploring different models and methods. The book also focuses on the journey of hair care products from laboratory testing to market, emphasizing clinical and preclinical assessments in compliance with global regulations. It highlights the role of ex-vivo hair follicle models in ensuring the safety and effectiveness of hair care products while providing a global regulatory framework. Additionally, the book explores the potential of artificial intelligence in predicting hair product toxicity, taking a global perspective. It delves into omics approaches for hair toxicity assessment, discussing current advances and future directions in this field. The next generation of hair products is also explored, with a focus on innovations that prioritize safe and healthy consumer choices. Finally, the book provides an overview of global regulatory frameworks for the hair care industry, including key agencies and guidelines. It serves as a valuable resource for professionals and researchers in the field, offering insights into the historical, scientific, and regulatory aspects of hair care products and their impact on consumer health and safety.

This book is a comprehensive review of the recent research on the lipotoxicity-related mechanisms in obesity and the development of new treatment strategies. In this second edition, the possible molecular treatment methods and their recent clinical approaches are discussed in addition to the basic mechanisms that are available and thoroughly reviewed previously. Moreover, all chapters have been reviewed, according to the current concepts and seven new chapters are added, covering obesity-related epigenetic modifications, senescence, obesity-related cancer development, endocrine disruptors, as well as nanotechnology-based clinical approaches. This book is an essential resource for clinicians and basic science researchers, such as biochemists, toxicologists, immunologists, nutritionists, adult and pediatric endocrinologists, and cardiologists, as well as all researchers or students who want to learn the mysteries of obesity.

This book addressed an in-depth comprehension of the classifications and characterizations of POPs, which have become global issues due to bioaccumulation, persistency, and toxicity. It represents the milestones of the development of pesticide application, industry, and management. Banned SC-POPs have special investigations. It discusses air-sea exchange, ocean currents, phase distribution, speciation, adsorption, desorption, and degradation as the key processes that control POP's fate. The book explores several aspects of POP chemistry that have a direct influence on their biochemical and toxicological consequences. The book illustrates the dynamic equilibriums influencing the proportion of a POP's gaseous, liquid, and solid phases. The book discussed POP migration by referring to the grasshopper effect. It also explores the impacts of climate change on emissions and the fate of POPs through a global-scale multimedia fate model. Additionally, it displays the impact of potential global change scenarios on POP bioaccumulation patterns. The book is directed at giving a deep discussion of the method's QA/QC process for POP determination and has verified the accuracy and precision of the procedures. As a distinctive point, it discusses many aspects concerning the toxicity of POPs. It reports mechanisms describing the toxicity of POPs on immune systems, carcinogenesis, endocrine, neural, and reproductive systems. The book keeps an eye on a model describing the global distribution and toxicity of PAHs. Among the exclusive points in the book is the evaluation of the recent ecological status in Egypt relative to POPs through a time-scale overview and recent case studies. It provides thematic literature related to DDC research in Africa through the WoS and Scopus databases from 1949 to 2021. The book emphasizes models for predicting the annual contribution rate of POPs as a way to raise public awareness about POPs. The greatest challenge for the book is how to motivate the audience to be aware of these hazardous materials in marine ecosystems. Moreover, this book will be of great interest to academics, professionals, practitioners, post-graduate students, and undergraduates because it gives a clear overview of POPs in the marine environment. It also provides decision-makers with a realistic perspective of the environmental file, allowing them to address environmental issues and directing stockholders to safer locations for environmental activity. From a future perspective, the regulation of pervasive POPs, with special reference to recently evaluated harmful substances (PFASs), has faced significant challenges in the wake of pressure from regulators.

This book is a compilation of all the necessary attributes associated with the knowledge of Persistent Organic Pollutants (POPs) that have been meticulously identified and charted down by the Stockholm Convention. Essential details starting from technical characteristics of the POPs to their expanse of nationwide usage, their remedial procedures adopted in India in comparison to available international data, and their consequent effects on biota and future perspectives are summarized with precision. Additionally, in-house scientific works that have been performed on each chemical are presented. Moreover, a unique feature of this book is that each chapter is dedicated to focusing on a single POP so that all the aspects of its usage, effects and fate can be accurately laid out. The book aims to be a go-to guidebook for stakeholders and academicians dealing with these chemicals who wish to be more acquainted with the present scenario of POPs and their status.

Arsenic contamination in drinking water and associated adverse outcomes is one of the major health issues in more than 50 countries worldwide. The scenario is getting even more detrimental with increasing number of affected people and newer sites reported from all over the world. Apart from drinking water, the presence of arsenic has been found in various other dietary sources. Threatening the health of millions of people due to arsenic's toxicity and carcinogenicity, the major routes of arsenic exposure for humans are either through drinking water or crops. This edited volume brings together a diverse group of environmental science, sustainability, and health researchers to address the challenges posed by global mass poisoning caused by arsenic water contamination. The book sheds light on this global environmental issue and proposes solutions to aquatic contamination through multi-disciplinary sustainable approaches and case studies from different parts of world. This book addresses the problem of arsenic by pursuing a holistic approach. It presents the status quo in different parts of the world and provides essential information on food-related arsenic exposure risks for humans and possible preventive and curative measures for tackling arsenic poisoning. The mechanisms of arsenic uptake, translocation, and distribution in plants and grains are also explained. In closing, the book reviews a variety of prospective sustainable solutions to the problem of arsenic accumulation in soil and water.The book comprises three sections. First section describes the routes of exposure to environmental arsenic and its transport in soil and aquatic ecosystems including its source and distribution in specific locations. Second section explains the health risks linked to arsenic exposure in food and the environment. Third section addresses sustainable arsenic contamination mitigation strategies using the potential applications of recent biotechnological techniques, bioremediation, phytoremediation, genetic engineering, nanotechnology, and in silico approaches.The book is intended for a broad audience including researchers, scientists, and readers with diverse backgrounds including agriculture, environmental science, food science, environmental management, and human health. It can also be used as an important reference guide for undergraduate and graduate students, university faculties, and environmentalists. The book may serve as a reference to environment and sustainability researchers, students, and policy makers.

This contributed volume brings out a comprehensive collection of information on environmental toxicology, its impact on living organisms in general and human health in particular. The main focus of this book is to address human health issues and risk assessment. Toxicological studies help in understanding the impact of harmful substances including both natural and synthetic chemicals on organisms and their environment. Contributions in the title include both laboratory and field based studies with a focus on human health. Moreover, day by day, there is an increase in the range of chemicals from pharmaceutical and other industries, agricultural runoffs, medicine, and many other sources which continuously contribute to the earth's chemical load. Almost all the countries are facing great difficulties in responding to the crucial and immediate need for effective management of such contaminants. The title compiles studies in regards to environmental toxicology and itseffect on human health. This book provides critical information and knowledge that can be used by regulatory agencies, decision-makers, policy makers, graduate and post-graduate students, researchers, environmental toxicologists, etc, and others to put programs and policies in place to limit our exposures to these substances thereby preventing or reducing the likelihood that a disease or other negative health outcomes would occur.

Effective drug delivery systems are essential in maximizing the therapeutic effects of the drugs in question. This book thoroughly analyses recent technological advances in new, nanomaterial-based drug delivery systems for the diagnosis and treatment of various diseases. These systems also have diverse applications in pharmaceutical, biomedical, biomaterial, and biotechnological fields. This book explains the different types of nanocarriers currently in development and covers both therapeutic and theranostic applications of drug-loaded nanocarriers and nanomedicine.Clinical research professionals, industrial pharmaceutical scientists, and veteran drug delivery developers benefit from the unique structure of this book, making it essential for the drug delivery researcher. Students, research scholars, and industrial professionals alike benefit from the current technological advancements, regulatory aspects, and the history of discovery and development in the field of nanomedicine presented in this book.

This book provides that knowledge needed to introduce individuals to the most important research and content on nanotoxicology in nanobiomedicine. Nanotechnology is helping to considerably improve, even revolutionize many technology and industry sectors: information technology, homeland security, medicine, transportation, energy, food safety, and environmental science, among many others. There is an urgent need for a general reference textbook that presents the most recent information on the toxicity and its effects in all these sectors, biomedicine in particular. It includes historical information, nanotoxicology by subject area and or disease, sources of nanomaterials, drug delivery systems and more. Scientists, researchers, and students in all fields that use nanotechnology will find this book essential reading.

This book is a collection of machine learning and deep learning algorithms, methods, architectures, and software tools that have been developed and widely applied in predictive toxicology. It compiles a set of recent applications using state-of-the-art machine learning and deep learning techniques in analysis of a variety of toxicological endpoint data. The contents illustrate those machine learning and deep learning algorithms, methods, and software tools and summarise the applications of machine learning and deep learning in predictive toxicology with informative text, figures, and tables that are contributed by the first tier of experts. One of the major features is the case studies of applications of machine learning and deep learning in toxicological research that serve as examples for readers to learn how to apply machine learning and deep learning techniques in predictive toxicology. This book is expected to provide a reference for practical applications of machine learning anddeep learning in toxicological research. It is a useful guide for toxicologists, chemists, drug discovery and development researchers, regulatory scientists, government reviewers, and graduate students. The main benefit for the readers is understanding the widely used machine learning and deep learning techniques and gaining practical procedures for applying machine learning and deep learning in predictive toxicology.

Microplastics and nanoplastics have been recently found in most environmental media and in living organisms, thus representing a serious health concern of yet poorly known adverse consequences. This book summarizes recent findings on the sources, behavior, transformation, toxicity and remediation of microplastics, with focus on soils, water, wastewater, air, soils, plants and corals. Advanced methods for sampling, characterization, removal and degradation of microplastics.

This handbook of the series Biomarkers in Disease informs comprehensively about all aspects of monitoring and detecting toxicity in the human body and model organisms. Biomarkers for assessing toxicity in diverse organs are presented and different assays and methods are explained. Single compounds and drugs and their toxicity for humans are shown and the methods for detection described. Similar to all the volumes of the Biomarkers in Disease series, the chapters are written by experts in their field, each chapter features key facts summarizing the most important aspects of its respective topic and the definitions of words and terms facilitate the reading and understanding. This handbook is a must-have for researchers in toxicology and biomedicine who analyze the effects of drugs and various other substances in the human body and in model organisms. It also serves as a thorough guide for clinicians and pharmacologists.

This book provides an overview of Data Monitoring Committees(DMC) - what was done in the past, what is currently being done, and thoughts on improvements for the future. Previous works focused primarily on large cardiovascular studies (where DMCs originated more than 30 years ago) but updated references are needed that discuss smaller, more flexible studies in areas such as oncology. The authors have attended ~800 DMC meetings from ~200 distinct studies across all areas of clinical studies (oncology, rheumatology, rare diseases, cardiology, immunology, etc.) This wide range of expertise will be used, as well as the expertise that comes from working with virtually every large biotechnology and pharmaceutical company and CRO for DMC work. The reader of the book will know when DMCs are needed or helpful, how to form the DMC, how to work with external CROs and with sponsor teams and the DMC to create needed DMC outputs, how the DMC meetings are conducted, and - especially for DMC members - what are considerations within the Closed Session to review safety/efficacy outputs to assess risk/benefit to make appropriate recommendations that protect the patient safety and trial integrity. This is a practical hands-on book on how to decide if a DMC is necessary, how to form the DMC, how to expertly create the necessary materials for the DMC and have smooth running DMC meetings. There is no specialized training in school about how DMCs work - frequently people may have been in industry for many years without ever needing to work with a DMC. This book is the helpful reference for those new to these DMCs. The DMC work is critical to be correctly implemented as the impact of DMC activity on safeguarding the trial is so important.This book provides the following: Provides thorough instructions on the steps needed to form and implement a Data Monitoring Committee for clinical trial evaluation;Includes practical and hands-on information on DMC implementation;Discusses a wide range of clinical trial – by phase and therapeutic area.

Reservoir construction is the key strategy for water resource management. In recent years, the migration of pollutants and their transformation into the reservoir ecosystem has become a global problem. Intensified anthropogenic activities and unsustainable practices have amplified the pollutant levels in the reservoir. Therefore, this book intends to highlight environmental characteristics of the reservoir, study methods of ecotoxicology, and mechanistic toxicogenetic pathways of pollutants in the reservoir. Adverse outcome pathway (AOPs) model is used to elucidate toxicological effects of reservoir pollutants. Moreover, ecological and human health risks of the Three Gorges Reservoir (TGR), the largest power generation reservoir on earth, and its pollution status are also discussed.

This book highlights the application of microfluidics in cell biology research, chemical biology, and drug discovery. It covers the recent breakthroughs and prospects of organ-on-a-chip, human-on-a-chip, multi-organ-on-a-chip for personalized medicine. The book presents the preclinical studies of organs-on-a-chip, concepts of multiple vascularized organ-on-chips, application of organ-on-a-chip in blood-brain barrier model, culture and co-culture of cells on multi-organ-on-chip and parameter measurements in microfluidic devices. It underscores the advantage of microfluidic devices for developing efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Further, it entails human-on-a-chip for measuring the systemic response as well as immediate effects of an organ reaction on other organs. In summary, this book reviews the development of a microfluidic-based organ-on-a-chip device for the preclinical evaluation,ADME studies of drugs, chemicals, and medical devices. This book is a valuable source for pharma companies, product developers, students, researchers, academicians, and practitioners.

Mycotoxins are the metabolites of fungus and are reported to contaminate nearly 25% of the food produced worldwide. The mycotoxins of most significance are the aflatoxins due to their severe health implications and their prevalence in food commodities on a larger scale. Aflatoxins are produced by certain species of fungi the most prominent among which are Aspergillus flavus, A. parasiticus and A. nominous. Food commodities of African and South Asian countries are especially reported to have aflatoxins well beyond the allowable limits but due to the global trade of food commodities developed countries are also prone towards the perils of aflatoxins. Moreover, climate changes may have a substantial impact on the distribution and global prevalence of aflatoxins in the near future.The International Agency for Research on Cancer (IARC) has classified the aflatoxins as group 1 category carcinogen. Aflatoxins are also reported as teratogenic, mutagenic, growth retardant, immunosuppressant and may also cause nervous system and reproductive system disorders. Preventive approaches involving good manufacturing from “farm to fork” are the major focus of the current food industry.The aim of our book is to provide readers with the most recent data and up-to-date studies from aflatoxins research, with specific focuses on (i) the impact of aflatoxins on human health, (ii) new approaches by the researchers from different parts of the world to degrade aflatoxins and (iii) potential preventive approaches that can significantly lessen the burden of aflatoxins in food products

Volume Two advances the exploration of the fundamental principles of oxidative stress and toxicity on male (and female) reproduction. It includes the advances in research on male reproductive health, the impact of environmental factors, the protective measures using bioactive compounds and traditional medicines, and how to limit toxic exposure. It includes coverage of: Oxidative stress and male infertilityEnvironmental stressors and sexual healthHeavy metals, pesticides, fine particle toxicity and male reproductionProtective measures against oxidative stress in gametes/embryos by using bioactive compounds/phytomedicines in Assisted Reproductive Technology (ART)Role of reactive oxygen species on female reproductionRadiation and mutagenic factors affecting the male reproductive systemBoth volumes provide a comprehensive look at the most basic concepts and advanced research being conducted by world famous scientists and researchers in male infertility and reproduction.

This book gives an overview of therapeutic drug monitoring (TDM) and its clinical application. It also highlights recent advances in toxicological studies, as they relate to therapeutic drug monitoring. This is one of the few books available on the market that covers TDM. Therapeutic drug monitoring (TDM) is a clinical decision-making tool that enables dosage regimen adjustments based on clinical and laboratory measurements. TDM not only involves the measuring of drug concentrations but also interpretation of the results. There is a strong correlation between drug concentrations in body fluids and outcome than between dose and outcome. The chapters include coverage of analytical techniques, pharmacokinetics, therapeutic indices, artificial intelligence and recent advances in toxicological studies.The book fills a gap in published literature and provides reliable information on; Analytical techniques in TDM and clinical toxicology TDM and pharmacokinetic studies TDM of drugs with narrow therapeutic indices Artificial intelligence in TDM and clinical toxicology Future directions and challenges

This book discusses the role of oxidative stress in human reproduction with a focus on men's health. The physiological roles of reactive oxygen species (ROS) in male fertility are the focus in this book. This topic is important because oxidative stress is a result of the imbalance between ROS and antioxidants in the body which may lead to sperm damage (DNA or count), deformity, and eventually, male infertility. Therefore, for a better understanding of the molecular mechanisms related to male genotoxicity and its regulation in infertility, this book provides an up-to-date view on the impact of oxidative stress factors in male reproduction. The main aim of this book is to collect a series of research articles and reviews from a diverse group of scientists to share their research work on the role of ROS or oxidative stress in physiological and pathological states in relation to (in)fertility in the male. This book presents various state-of-the-art chapters of the recent progress in the field of cellular toxicology and clinical manifestations of various issues related to men's health and fertility. Topics include cell signaling, DNA damage and infertility, the pathophysiology of disease instigation and distribution, immune toxicity and prevention.

The main aim of this book is to collect a series of research articles and reviews from a diverse group of scientists to share their research work on the role of free radical research and environmental toxicity. This book presents various state-of-the-art chapters of recent progress in the field of cellular toxicology and clinical manifestations of various disorders. Topics include cell signaling, various risk factors, the pathophysiology of disease instigation and distribution, mechanistic insights into metal and nanoparticle toxicity, neural toxicity, nongenotoxic carcinogenicity, immune and idiosyncratic toxicity, prevention, biomarkers related to disease progression and therapeutic strategies. In particular, this book provides valuable insight for researchers, pathologists, and clinicians with an interest in toxicological research and cellular impairments with special emphasis on therapeutic advancement.

Since its advent, nanotechnologies are considered key enabling technologies that take advantage of a wide array of nanomaterials (NMs) for biomedical and industrial applications generating significant societal and economic benefits. However, such innovation increases human exposure to these substances through inhalation, ingestion or dermal contact raising public health concerns. Furthermore, the NMs'specific physicochemical properties, that confer them unique beneficial characteristics, can also elicit nano-bio interactions leading to toxicity and concerns for public health. In addition, such properties can be affected by the surrounding matrix, particularly when incorporated in complex matrices such as food products, leading to secondary features potentially more relevant than primary characteristics for determining their toxicological outcome. These nano specific issues raise the question of whether the NMs may produce adverse outcomes that are not accounted for when usingconventional toxicological approaches to assess their safety. Such uncertainties about the safety of NMs for human health and the environment may hamper a faster and more widespread exploration of their potentials. In response, the NMs definition has evolved, and nanotoxicology has developed towards new and more integrative approach methods to support regulatory and policy actions. This book provides a perspective on recent developments in the synthesis, application, and characterization of NMs and the related nanotechnologies, focusing on nanotoxicology for their accurate safety assessment early in the product development stage. The use of complex in vitro models, including multicellular systems and organoids, and “omics-based” approaches, such as transcriptomics or epigenomics, have greatly contributed to an in-depth understanding of the cellular and molecular mechanisms behind some NMs toxicity. Such mechanistic knowledge is equally addressed in this book and has set the basis for a predictive nanotoxicology approach building on adverse outcome pathways. In addition, considering the knowledge provided by the above-mentioned approaches, insights into risk assessment, standardization, and regulation of NMs are also included. Incorporating adequate nanosafety assessment early in the life-cycle of NMs will allow the implementation of the safe and sustainable-by-design paradigm enabling safety to keep pace with innovation. Chapters 10 and 15 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

“This book uses Caenorhabditis elegans as model animal to introduce the toxicity induction of toxicants at environmentally relevant concentrations under different conditions. It also discusses the systematic introduction of different molecular signaling pathways, as well as G protein coupled receptors and ion channels, in regulating the toxicity of toxicants at environmentally relevant concentrations. The intestinal, neuronal, and germline molecular networks required for the regulation of toxicity of toxicants at environmentally relevant concentrations is further introduced and discussed. This book aims at providing a systematic understanding of the knowledge system on toxicology at environmentally relevant concentrations in Caenorhabditis elegans. ”

The book covers the area of ‘Nanotoxicology'but primarily from the point of view of nanotoxicology at the interface with other disciplines including human toxicology; environmental toxicology; characterization, dose and transformations; regulation; public and elite group perceptions; and interactions with innovation.Nanotoxicology in Humans and the Environment is written for researchers in nanotoxicology in academia, industry, government, and research students. Given the rapid development, the maturing of the discipline and its importance in current regulation and industry development (eg REACH, TSCA), the book is very timely.

This volume describes the identification of emerging organic pollutants, mainly from industrial sources, their associated toxicological threats, and the latest green methods and biotechnological solutions to abate harmful impacts on people and the environment. The chapters present reviews on current applied toxicology research, occupational health hazards and green remedial solutions for pollution control in terrestrial and aquatic environments, with the aim of raising public awareness of these issues and providing chemists, toxicologists and environmental scientists with the knowledge to combat organic pollutants through sustainable means. Readers will learn about the multi-dimensional applications of materials and processes which harvest energy out of environmental remediation technologies, as well as the roles of biotechnology and nanotechnology in addressing high pollutant load. Specific attention is paid to technologies that draw energy through wastewater remediation, as this covers the primary means by which organic pollutants are introduced into the environment from industry and other sources. The book will be of use to pollution control boards, industry regulators, and students and researchers in the fields of biotechnology, biomedical science, hydrology and water chemistry.

Over the years, India has attained a prominent global position in the manufacture of Generic Drugs. This success can be attributed to its synthetic organic chemistry and chemical engineering strengths, nurtured by the timely policies of the Government of India. However, breakthrough successes in New Drug Discovery have remained elusive, despite the brilliant and sustained efforts of many Indian researchers and Pharma establishments. The Indian National Science Academy thought it appropriate to document India's New Drug Discovery Research (NDDR) journey to date. Gathering contributions from prominent researchers in the Indian Pharma Industry and Academia, this book highlights their efforts, achievements, and the status quo of Indian NDDR.

This book presents recent reviews on the occurrence, analysis, toxicity and remediation of pesticides in biological systems such as fish, chickens, water, soil and food.

This book reviews advanced techniques for the determination of pesticide residues, with focus on extraction, detectors and cleaning protocols. Chapters also discuss pesticide occurrence, toxicity and remediation.

This book illuminates mechanisms of resilience. Threats and defense systems lead to adaptive changes in gene expression. Environmental conditions may dampen adaptive responses at the level of RNA expression. The first seven chapters elaborate threats to human health. Human populations spontaneously invade niche boundaries exposing us to threats that drive the resilience process. Emerging RNA viruses are a significant threat to human health. Antiviral drugs are reviewed and how viral genomes respond to the environment driving genome sequence plasticity. Limitations in predicting the human outcome are described in “nonlinear anomalies.” An example includes medical countermeasures for Ebola and Marburg viruses under the “Animal Rule.” Bacterial infections and a review of antibacterial drugs and bacterial resilience mediated by horizontal gene transfer follow. Chapter 6 shifts focus to cancer and discovery of novel therapeutics for leukemia. The spontaneous resolution of AML in children with Down syndrome highlights human resilience. Chapter 7 explores chemicals in the environment. Examples of chemical carcinogenesis illustrate how chemicals disrupt genomes. Historic research ignored RNA damage from chemically induced nucleic acid damage. The emergence of important forms of RNA and their possible role in resilience is proposed. Chapters 8-10 discuss threat recognition and defense systems responding to improve resilience. Chapter 8 describes the immune response as a threat recognition system and response via diverse RNA expression. Oligonucleotides designed to suppress specific RNA to manipulate the immune response including exon-skipping strategies are described. Threat recognition and response by the cytochrome P450 enzymes parallels immune responses. The author proposes metabolic clearance of small molecules is a companion to the immune system. Chapter 10 highlights RNA diversity expressed from a single gene. Molecular Resilience lists paths to RNA transcriptome plasticity forms the molecular basis for resilience. Chapter 11 is an account of ExonDys 51, an approved drug for the treatment of Duchenne muscular dystrophy. Chapter 12 addresses the question “what informs molecular mechanisms of resilience?” that drives the limits to adaptation and boundaries for molecular resilience. He speculates that radical oxygen, epigenetic modifications, and ligands to nuclear hormone receptors play critical roles in regulating molecular resilience.

​This volume contains a collection of writings from the leaders in the fields of Molecular Biology and Melanoma Research which will begin to tell the ever-expanding story of the most recent findings, discoveries, and potential of BRAF-directed targets in melanoma. Recent research has shown that BRAF inhibitors are effective for a short period of time, but there is little hope that this drugs as single agents will lead to durable benefit in a majority of patients. Among scientists and researchers who work in drug discovery, there is a lot of interest in the development of molecularly targeted cancer agents. Namely, the identification of a molecular target, the selection of molecules which effectively inhibit this target. What is starkly different about the development of this class of compounds, however, is that the mechanism of action of these agents are not as straightforward as was once previously assumed and the mechanisms of resistance that tumor cells employ to evade complete destruction are unlike any that have been described before. These discoveries in addition to utilization of modern molecular biology techniques have led to a series of hypotheses regarding which other types of molecules could be used in combination with BRAF-inhibitors in hopes of revolutionizing the potential of therapeutics in melanoma.

This book provides critical reviews of the role of neurotrophins and their receptors in a wide variety of diseases including neurodegenerative diseases like Huntington's syndrome, cognitive function, psychiatric disorders such as clinical depression, Rett syndrome, motoneurone disease, spinal cord injury, pain, metabolic disease and cardiovascular disease. It also contains contributions from leaders in the field dealing with the basic biology, transcriptional and post-translational regulation of the neurotrophins and their receptors. The present book will review all recent areas of progress in the study of neurotrophins and their biological roles.

A comprehensive overview of the effects of trichloroethylene toxicity caused by real-life exposure levels highlighting how exposure to trichloroethylene may contribute to the etiology of several idiopathic human diseases. Discussion will focus on different kinds of modeling and how they may be used to predict functional consequences and to dissect the contribution of different mechanistic pathways, including potential mechanisms of action for trichloroethylene toxicity in different organ systems. It will explore the role of epigenetic alterations in trichloroethylene toxicity, this provides important mechanistic information and may also provide the basis for intervention therapy. Chapters will also explain how the risks from trichloroethylene exposure may be greater in certain populations based on genetic predisposition, age of exposure and co-exposure to other chemicals With contributions from international experts in the field, Trichloroethylene: Toxicity and Health Risks is an essential resource for researchers and clinicians in toxicology, immunology, medicine and public health as well as industry and government regulatory scientists involved in safety and health protection and epidemiologists, highlighting the need for interdisciplinary cooperation in solving issues of environmental toxicity.

​​​The imbalance between rapidly proliferating tumor cells and inadequate and inefficient tumor vasculature leads to a decrease in oxygen levels (hypoxia and/or anoxia) in tumor tissues. Intra-tumor hypoxia profoundly affects the biological behavior of cancer cells, which become resistant to conventional therapies and acquire a more invasive and metastatic phenotype. Hypoxia is a hallmark of the malignant phenotype and a key feature of the tumor microenvironment. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation. HIF triggers the expression of genes whose products induce angiogenesis, decrease oxygen consumption, switch metabolism to glycolysis, maintain a stem cell phenotype and select for more invasive and metastatic cells. Therapeutic approaches targeting HIF, directly or downstream mediators of its transcriptional activity, are being developed. Intra-tumor hypoxia is a topic has been gaining scientific interest over the last few years for its wide involvement in many physiological and pathological processes. This volume will cover the latest research and translational aspects associated with intra-tumor hypoxia, along with opportunities for drug development offered by this unique feature of the tumor microenvironment. The ongoing efforts to translate our understanding of the biology underlying intra-tumor hypoxia in viable therapeutic options face many challenges, but this book will provide an opportunity for an in-depth analysis of the fundamental mechanisms implicated in the adaption to low oxygen levels and will scrutinize the potential for opportunities that are being pursued in both research and the drug development industry.

This volume focuses on current evidence-based pharmacological treatments of various forms of pulmonary hypertension and provides a comprehensive review of the latest developments in this area. The first part of the book covers the definition, classification, pathophysiology, pathology, biomarkers and animal models of the disease, thus laying the conceptual basis for what follows. The middle section provides an overview of the established therapies, such as calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and inhaled nitric oxide. The last section explores novel pathways and emerging therapeutic approaches including soluble guanylate cyclase stimulators, Rho-kinase inhibitors, inhibitors of serotonin receptors and transporters, peptide growth factors, vasoactive peptides, modulators of redox equilibrium and cyclic nucleotide homeostasis, as well as immunosuppressive and anti-proliferative agents. Particular attention is given to the clinical applications of these experimental therapies, that are on the horizon. The book thus spans the continuum from basic science to clinical applications.

Adverse drug reactions and interactions are still a major headache for healthcare professionals around the world. The US Food and Drug Administration's database recorded almost 300,000 serious adverse events in 2009 alone, of which 45,000 instances proved fatal. This updated new edition of the indispensable guide to drug interactions incorporates fresh research completed since the book's original publication by Humana Press in 2004. Additions include a new section on pharmacogenomics, a rapidly growing field that explores the genetic basis for the variability of responses to drugs. This new material reviews important polymorphisms in drug metabolizing enzymes and applies the findings to forensic interpretation, using case studies involving opiates as exemplars.Existing chapters from the first edition have in most cases been updated and reworked to reflect new data or incorporate better tables and diagrams, as well as to include recent drugs and formulations. Recent references have been inserted too. The handbook features extra material on illicit drug use, with a new chapter tackling the subject that covers cocaine, amphetamines and cannabis, among others. The section on the central nervous system also deals with a number of drugs that are abused illicitly, such as benzodiazepines, opiates flunitrazepam and GHB, while so-called'social'drugs such as alcohol and nicotine are still discussed in the book's section on environmental and social pharmacology. Focusing as before on detailed explanation and incorporating both pharmacokinetic and pharmacodynamic drug interactions, this book will continue to be a lodestar for health and forensic professionals as well as students.

The term “heavy metals” is used as a group name of toxic metals and metalloids (semimetals) causing contaminations and ecotoxicity. In strict chemical sense the density of heavy metals is higher than 5 g/cm3. From biological point of view as microelements they can be divided into two major groups. a. For their physiological function organisms and cells require essential microelements such as iron, chromium (III), cobalt, copper, manganese, molidenium, zinc. b. The other group of heavy metals is toxic to the health or environment. Of highest concern are the emissions of As, Cd, Co, Cu, Hg, Mn, Ni, Pb, Sn, Tl. The toxicity of heavy metals is well known at organizational level, while less attention has been paid to their cellular effects. This book describes the toxicity of heavy metals on microorganisms, yeast, plant and animal cells. Other chapters of the book deal with their genotoxic, mutagenic and carcinogenic effects. The toxicity of several metals touch upon the aspects of environmental hazard, ecosystems and human health. Among the cellular responses of heavy metals irregularities in cellular mechanisms such as gene expression, protein folding, stress signaling pathways are among the most important ones. The final chapters deal with biosensors and removal of heavy metals. As everybody is eating, drinking and exposed to heavy metals on a daily basis, the spirit of the book will attract a wide audience.

Small animal imaging has been recognized as an important tool in preclinical research. Nevertheless, the results of non-invasive imaging are often disappointing owing to choice of a suboptimal imaging modality and/or shortcomings in study design, experimental setup, and data evaluation. This textbook is a practical guide to the use of non-invasive imaging in preclinical research. Each of the available imaging modalities is discussed in detail, with the assistance of numerous informative illustrations. In addition, many useful hints are provided on the installation of a small animal unit, study planning, animal handling, and the cost-effective performance of small animal imaging. Cross-calibration methods, data postprocessing, and special imaging applications are also considered in depth. This is the first book to cover all the practical basics in small animal imaging, and it will prove an invaluable aid for researchers, students, and technicians.

This book attempts to analyze the latest discoveries in sphingolipid biology and how the alteration of their metabolism leads to altered signaling events and to the development of pathobiological disorders, such as cancer, cardiovascular diseases, asthma, diabetes, inflammation and infectious diseases.

In this monograph about gene therapy of autoimmune and inflammatory d- orders we have gathered international experts and leaders from different fields to review the state of the art advances on topics ranging from disease entities to vectors and engineered cells. The different approaches described in each chapter take into consideration the biomedical knowledge of these diseases and address the complexities of delivering long-term genetic interventions. Gene therapy also serves as a testing ground for new therapeutic entities and helps provide proof of principle for their potential therapeutic role in animal models of disease. Scaling up from mice to men still remains an important h- dle not only from the quantitative point of view, but also for currently unknown and unexpected secondary effects of the vector or the transgene. Some of these approaches have already been tested in the clinic, but much more needs to be done to understand the human conditions treated and the n- ural history of their pathology. We are indebted to the secretarial assistance of Ms. Lin Wells (Bone and Joint Research Unit, London, UK) and the help of Hans Detlef Klüber for his help in getting this book published. We hope this book will be of interest to c- nicians and scientists and inspiring to students of the subject who will use their own ingenuity and knowledge to further forward this discipline into clinical use.

A huge effort is put into the science of nanoparticles and their production. In many cases it is unavoidable that nanoparticles are released into the environment, either during the production processes or during the use of a product made from these particles. It is also realized that combustion processes like traffic and power plants release nanoparticles into the atmosphere. However it is not known how nanoparticles interact with the human body, especially upon inhalation. At the same time research activities are devoted to understand how nano-sized medicine particles can be used to administer medicines via inhalation. In any case it is absolutely necessary to know how the nanoparticles interfere with the inhalation system, how they deposit and affect on the human system. Three main themes are discussed: Nanoparticle sources and production Nanoparticle inhalation and deposition Toxicological and medical consequences of nanoparticles Each theme is covered comprehensively, starting at nano-quantum effects up to technical and medical applications such as measuring equipment and inhalation instrumentation. This book brings together all sub-disciplines in the field related to aerosol nanoparticles. Each chapter is written by a world expert, giving the state of the art information and challenging open questions. The last chapter summarizes in an interdisciplinary way what is already known and what still is ahead of us.

Preface Tumor development and progression occur as a result of cumulative acquisition of genetic alterations affecting oncogenes and tumor suppressor genes. As a consequence of these alterations the arising tumor gains some fatal properties such as increased cell proliferation and decreased apoptosis, resulting in a net accumulation of tra- formed cells. Once a critical volume is achieved, lack of oxygen and nutrients limits further growth. To overcome this obstacle, the tumor cells initiate a program focused on the formation of new blood vessels within the host tissue. This process is termed tumor angiogenesis and contributes to the progression of most solid tumors and the formation of metastases. Since its discovery more than 30 years ago by Dr. Judah Folkman, tumor angiog- esis has been proposed as an ideal target for novel tumor therapies. Today the first anti-angiogenic compounds are available for the treatment of patients but their s- cess in the clinic is rather limited when given as monotherapies. This is in contrast to many preclinical results which revealed a much higher efficacy of these therapeutics in appropriate animal models. The reasons for this discrepancy are manifold, one being the existence of more than one angiogenic signaling system capable of driving tumor angiogenesis. Therefore it is no surprise that the inhibition of just one system is not sufficient to block the formation of new blood vessels in patients.

Alzheimer's disease (AD) is a neurodegenerative disease that robs the minds of our elderly population. Approximately one in every eight adults over the age of 65 and nearly half of those over 85 are afflicted with this disease. The aging population in developed societies will impose an ever increasing socioeconomic threat in the future. Current medicines for AD patients are mainly symptomatic treatments and a huge unmet medical need exists to slow the progression of this disease. A great deal of research has been dedicated to understanding the pathogenesis of AD from which comes many ideas for intervening with its progression. Some of these ideas have been fast-tracked to clinical trials due to the availability of medicines with proven clinical efficacies for other diseases (e.g. atorvastatin, simvastatin, rosiglitazone and clioquinol) while others represent novel chemical entities (e.g. glycogen synthase kinase-3 inhibitors). This volume will first review existing cholinesterase inhibitors prescribed for AD patients followed by some target mechanisms with ongoing clinical trials. It offers a glimpse of what our future medicine cabinets may look like for AD patients. It also provides an interesting read on why and how current medicines for other indications could potentially be used to treat AD.

Das Wissen über die molekularen Grundlagen der Medizin und seine Anwendung in der klinischen Medizin nimmt mit ungebrochener Dynamik zu. Die 3. Auflage des Buches reflektiert diese Entwicklung: In 22 Kapiteln werden allgemeine Grundlagen, experimentelle Modelle, Diagnostik und Therapie auf dem neuesten Kenntnisstand von ausgewiesenen Experten dargestellt. Neu hinzugekommen sind Kapitel über die Themen, deren zentrale Bedeutung für die Zukunft der Molekularen Medizin absehbar ist: Pharmakogenetik, Pharmakogenomik, Gentherapie, Bioinformatik und biotechnologische Anwendungen. Die ideale Wissensgrundlage für Interessierte aus allen Fachgebieten, die an den Fortschritten der Molekularen Medizin teilhaben wollen!

Nanomedicine is clinical medicine with the application of nanobiotechnology, which is currently being used to research the pathomechanism of disease, refine molecular diagnostics, and aid in the discovery, development and delivery of drugs. In The Handbook of Nanomedicine, Prof. Kewal K. Jain distills the voluminous literature relevant to the subject into one concise, comprehensive and easy-to-use guide. Beginning with the basics, the subject is developed to potential clinical applications, many of which are still at an experimental stage. Important components of nanomedicine such as nanodiagnostics and nanopharmaceuticals are covered extensively. As this text is aimed at nonmedical scientists, pharmaceutical personnel, as well as physicians, descriptions of the technology involved and other medical terminology are kept as clear and simple as possible. In depth and cutting-edge, The Handbook of Nanomedicine informs its readers of the ever-growing field of nanomedicine, destined to play a significant role in the future of healthcare.

After more than twenty years of use Good Laboratory Practice, or GLP, has attained a secure place in the world of testing chemicals and other'test items'with regard to their safety for humans and the environment. Gone are the days when the GLP regulations were hotly debated amongst scientists in academia and industry and were accused of stifling flexibility in, imaginative approaches to, and science-based conduct of, all kinds of studies concerned with toxic effects and other parameters important for the evaluation and assessment of products submitted for registration and permission to market. The GLP regulations have developed from rules on how to exactly document the planning, conduct and reporting of toxicity studies to a quality system for the management of a multitude of study types, from the simple determination of a physical/chemical parameter to the most complex field tests or ecotoxicology studies. At the same time the term'Good Laboratory Practice'has become somewhat of a slogan with the aim to characterise any reliably conducted laboratory work.