In the last decade and a half, great progress has been made in the development of concepts and models for mixture toxicity, both in human and environmental toxicology. However, due to their different protection goals, developments have often progressed in parallel but with little integration. Arguably the first book to clearly link ecotoxicology and classic human toxicology, Mixture Toxicity: Linking Approaches from Ecological and Human Toxicology incorporates extensive reviews of exposure to toxicants, toxicokinetics and toxicodynamics, toxicity of mixtures, and risk assessment. The book examines developments in both fields, compares and contrasts their current state of the art, and identifies where one field can learn from the other. Each chapter provides an essential overview of the state of the art in both human and ecotoxicological mixture risk assessment, focusing on the work published in the last fifteen years. The coverage progresses from exposure to risk assessment, at each step identifying the special complications typically raised by mixtures. Based on in-depth discussions among specialists representing different disciplines and approaches, the chapters each address: Exposure - how to quantify the amounts of chemicals that may enter the living organism Kinetics, dynamics, and metabolism - how the chemicals enter an organism, travel within the organism, how they are metabolized and reach the target site, and explain development of toxicity with time Toxicity - what are the chemicals' detrimental effects on the organism Test design and complex mixture characterization - how chemicals interact, how to measure effects of mixtures, and how to identify responsible chemicals Risk assessment - how to assess for risks in humans and the environment An unusual combination of different points of view on exposure to and risk assessment of chemical mixtures, this book summarizes current knowledge on combined effects of toxicant mixtures, information that is generally only available in a very fragmented form as individual journal papers. It identifies possible crosslinks and includes recommendations for mutual developments that can improve the state of knowledge on mixture toxicity and ultimately lead to better and more integrated risk assessment.

This book will provide the latest advances in molecular and cellular biology for establishing the foundation of a complete understanding of the mechanisms of breast differentiation leading to cancer prevention. The authors are based on the epidemiological evidence indicating that early first full term pregnancy is a protective factor in human against breast cancer and they have used this paradigm and developed experimental systems in both in vivo and in vitro that have demonstrated mechanistically how the differentiation at the organ and cellular level takes place. This knowledge has provided the blueprint for developing better understanding of the basis of cancer prevention. The transcriptoma analysis of the breast of pre and post-menopausal women has established a genomic signature imprinted in the breast that differs according to the reproductive history of the woman showing that early first full term pregnancy reprogram the organ. This reprogramming takes place at the chromatin level by changing the transcriptional process. The modification of the transcriptional control is due to the expression of non coding RNA sequences and posttranscriptional control driven by the splicesome. The plasticity of the genome of the human breast make possible this reprogramming that is not only induced by the physiological process of pregnancy but by the use of hormones that mimic pregnancy without pregnancy. The author have established the basis of clinical trials for prevention and the discovery that short 15aa peptides of the chorionic gonadotropin hormone can be used in human breast cancer prevention based on preclinical and clinical data.

Quantitative structure-activity relationships (QSARs) represent predictive models derived from the application of statistical tools correlating biological activity or other properties of chemicals with descriptors representative of molecular structure and/or property. Quantitative Structure-Activity Relationships in Drug Design, Predictive Toxicology, and Risk Assessment discusses recent advancements in the field of QSARs with special reference to their application in drug development, predictive toxicology, and chemical risk analysis. Focusing on emerging research in the field, this book is an ideal reference source for industry professionals, students, and academicians in the fields of medicinal chemistry and toxicology.

This book is meant to provide a complete overview of the research of HPV and its connection to cervical cancer.

The brain is protected by the blood-brain barrier and this barrier prevents many drugs from entering the brain. This volume discusses various drug delivery and targeting strategies that are being developed to enhance the transport and distribution of drugs into the brain.

* Discusses new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

This second edition book explores breakthrough technologies in the field of drug target identification and validation. The volume emphasizes particularly revolutionary technologies, such as CRISPR-related screening, "big data," and in silico approaches, as well as in vivo applications of CRISPR and best uses of animal models in drug development. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Fully updated and authoritative, Target Identification and Validation in Drug Discovery: Methods and Protocols, Second Edition is an ideal guide for molecular and cellular biologists, pharmacologists, pathologists, bioinformaticians, clinical researchers, or investigators, as well as experts in other fields that need a quick overview of these state-of-the-art technologies.

Exposure to ambient air pollutants, both indoors and outdoors has been associated with the exacerbation and also in the etiology of diverse human diseases. This book offers an overview of our current understanding of air pollution health risks and how this knowledge is being used in the regulatory, therapeutic intervention measures to protect the public health and reduce the disease burden caused by acute and long-term exposure to air pollutants. Air Pollution and Health Effects provides readers with a comprehensive understanding of air pollution health risks, morbidity and the global disease burden, whilst also delivering critical review on state of the art research so as to gain a fundamental understanding of the biological mechanisms involved in the etiology of air pollution-induced diseases. Chapters range from pregnancy outcomes and pre-term birth, carcinogens in the ambient aerosol and the health consequences of indoor biomass burning. Special emphasis is placed on regional and local air pollution and its impact on global health along with suitable preventive and interventional measures. With contributions from international experts in the field this volume is a valuable guide for researchers and clinicians in toxicology, medicine and public health as well as industry and government regulatory scientists involved in health protection.

In this book, leading international experts analyze state-of-the-art advances in gene transfer vectors for applications in inherited disorders and also examine the toxicity profiles of these methods. The authors discuss the strengths and weaknesses of available vectors in the clinical setting, and specifically focus on the challenges and possible solutions that researchers are testing in order to improve the safety of gene therapy for genetic diseases. This comprehensive and authoritative overview of vector development is a necessary text for researchers, toxicologists, pharmacologists, molecular biologists, physicians, and students in these fields.

Cardiovascular disease remains a major cause of death and disability in developed countries and, increasingly so, in the developing world.Presented in this volume of Advances in Pharmacology are some of the most promising possibilities for treating large numbers of individuals afflicted with these conditions

This volume contains up-to-date reviews of the most important emerging cardiovascular therapies written by world leaders in the field."

This is the ideal book for anyone contemplating starting a career in, or shifting their career to, studying the dynamics that drive cancer progression and its response to therapy. Topics include the theory and population genetics of cancers, genetic diversity within tumors (intra-tumor heterogeneity), understanding how mutant clones expand in tissues, the role of cancer stem cells in the dynamics of tumors, the evolution of metastasis, and how to improve cancer therapy by addressing the evolution of cancers in response to our interventions. There are also chapters on the patterns of cancer susceptibility in humans due to a mismatch between our modern environment and the environment in which our ancestors evolved, as well as a chapter on the evolution of cancer suppression mechanisms that have evolved in different species, particularly the large long-lived animals like elephants and whales that are better at suppressing cancers than humans. This book serves as a primer on the evolutionary and ecological theory of cancer- the framework upon which all the details of cancer may be hung. It is ideal for oncologists and cancer researchers interested in evolutionary theory, and evolutionary biologists and ecologists interested in gaining insights into cancer development and prevention.

"Annual Reports in Medicinal Chemistry "provides timely and critical reviews of important topics in medicinal chemistry together with an emphasis on emerging topics in the biological sciences, which are expected to provide the basis for entirely new future therapies.
* Covers findings related to cardiovascular, inflammation, and pulmonary diseases
* Examines issues in oncology, from mTor inhibitors to drug targets
* Incorporates up-to-date information on drug design and discovery, including delivery to market

Cardiovascular disease remains a major cause of death and disability in developed countries and, increasingly so, in the developing world. Presented in this volume of Advances in Pharmacology are some of the most promising possibilities for treating large numbers of individuals afflicted with these conditions

This volume contains up-to-date reviews of the most important emerging cardiovascular therapies written by world leaders in the field.

Following 50 years of glucocorticoid use in a clinical setting, an international body of expert scientists and physicians presents the most expansive survey of glucocorticoid pharmacology to date. This work traces the history of glucocorticoid biology from the seminal description of glucocorticoid insufficiency by Thomas Addison in the mid-19th century, up to current advances in elucidating the molecular basis of glucocorticoid action. Important discoveries are presented, as well as milestones in drug development, a survey of current clinical practice, and prospects for novel glucocorticoid-based therapeutics. Scientists and clinicians will appreciate the scope of this work, which is of special interest to workers in the fields of endocrinology, inflammation and autoimmune disease.

The chemistry of phenols tends to be ignored in organic chemical textbooks and to be lost amongst the many classes of functional derivatives. This volume is not intended to provide a textbook approach but rather to give an account of developments in phenol chemistry in the last two decades.

Features of this book:

- Numerous phenolic systems have been covered in detail, e.g. phenolic propanoids.

- The emphasis throughout has been on synthesis, on what can be achieved by the use of phenolic intermediates and in the construction of phenolic end products.

- Many chapters enable the reader to refer to the original literature wherever possible.

- Various chapters provide a fund of tutorial material and problems for undergraduate studies and further, which will encourage perusal of the literature. Some 2000 references to applied and academic papers are given.

Phenols are ubiquitous substances and now it is more widely accepted that there are pros and cons connected with their usage. The pros for compounds are well-known and are illustrated by perennial panaceas such as aspirin, paracetamol, codeine, etc. The cons are less obvious because they are also materials deeply entrenched in our standard of living and in most cases inherent hazards have only recently come to light. The book will be of interest to postgraduate students in academic and industrial work.

In response to the tremendous increase in the number of protein and peptide drugs, this treatise critically reviews transport and metabolism mechanisms relating to the delivery of endogenous and recombinant proteins to mammalian organs, tissues, and cells. It will promote fruitful collaboration among academic and industrial scientists in the fields of pharmacology, cell biology, biochemistry, physiology, and immunology.

The book deals with various clinical aspects of cytochrome P450 2E1 (CYP2E1), which is a potent source for oxidative stress. Oxidative stress is critical for pathogenesis of diseases and CYP2E1 is a major contributor for oxidative stress. Several clinical disorders are associated with changes in regulation of CYP2E1 and the consequent abnormalities, which include alcoholic liver disease, alcoholic pancreatitis, carcinogenesis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, obesity, hepatitis C virus infection, reproductive organ toxicity, hepatocellular and cholestatic liver cirrhosis, inhibition of bone repair, cross- tolerance in smokers and people treated with nicotine, disorders of the central nervous system, changes in metabolism of protoxicants in the circulatory system and susceptibility to human papillomavirus infection. Hence, CYP2E1 emerges as a new and potent player in aggravating injury and furthering disease complications.

This book provides a comprehensive review of both traditional and cutting-edge methodologies that are currently used in computational toxicology and specifically features its application in regulatory decision making. The authors from various government agencies such as FDA, NCATS and NIEHS industry, and academic institutes share their real-world experience and discuss most current practices in computational toxicology and potential applications in regulatory science. Among the topics covered are molecular modeling and molecular dynamics simulations, machine learning methods for toxicity analysis, network-based approaches for the assessment of drug toxicity and toxicogenomic analyses. Offering a valuable reference guide to computational toxicology and potential applications in regulatory science, this book will appeal to chemists, toxicologists, drug discovery and development researchers as well as to regulatory scientists, government reviewers and graduate students interested in this field.

This fully updated volume utilizes the expertise of scientists currently engaged in immunotoxicity testing to provide the reader with lab-ready procedures and the background information needed to identify effective testing approaches. Dedicated to identifying and describing exogenous agents that can modify immune function, uncovering modes and mechanisms of action for such agents, and translating data from the laboratory and from the clinic to better predict health risks as well as benefits to those who are exposed to immunomodulatory agents, immunotoxicity testing continues to be a vital field of study, and this collection highlights both the "tried and true" methods as well as alternative protocols that have been more recently developed. Written in the highly successful Methods in Molecular Biology format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Immunotoxicity Testing: Methods and Protocols, Second Edition serves as a valuable contribution to the continued evolution and the application of immunotoxicity testing.

This volume gathers the latest exciting findings on ADP-ribosylation from renowned experts in the field. It includes ten chapters, organized into the following three thematic sections: * Evolution and detection of endogenous ADP-ribosylation * ADP-ribosylation by the ARTC family of ADP-ribosyltransferases (R-S-E ARTs) * ADP-ribosylation by the ARTD family of ADP-ribosyltransferases (H-Y-E ARTs) The book will provide readers a better understanding of ADP-ribosylating toxins and their endogenous relatives. This provides a basis for developing novel toxin-neutralizing drugs and drugs targeting endogenous ADP-ribosyltransferase relatives.

This monograph was assembled to honor Professor Norman Bowery and his work on the 30th anniversary of his discovery of the GABAB receptor. In the present volume, leading neuroscientists from academia and industry provide a perspective of current research, both basic and translational, in the discovery of drugs acting at the GABAB receptor. The topics covered provide a comprehensive review of the field and the current state of research in this area. Included are chapters on the chemistry of GABAB agonists and antagonists, on the genetics and molecular composition of the site, its regulation and trafficking, and its role in controlling cellular, autonomic, and behavioral function. There are also chapters describing the potential clinical utility of drugs regulating GABAB activity receptorin the areas of hypertension, gastroesophageal reflux disease, Down syndrome, depression, and substance abuse.

The information contained in this text will be of particular interest to neuroscientists in general and to neuropharmacologists in particular.
Articles written by leading investigators in the fieldInforms and updates on all the latest developments"

This book provides multidisciplinary reviews of the mechanism of action and uses of methotrexate in the treatment of cancer, psoriasis, gynecologic and inflammatory diseases. The intended audience is composed of clinicians involved in the care of patients suffering from oncologic, gynecologic, rheumatic diseases as well as scientists involved in research into the pathogenesis and treatment of these diseases. This book is unique in that it provides a single, state-of-the-art source for information regarding the mechanism and use of methotrexate in many different areas of medicine.

Get the most from your study time, and experience a realistic USMLE simulation with Rapid Review Pharmacology, 3rd Edition, by Drs. Thomas Pazdernik and Laszlo Kerecsen. This new edition in the highly rated Rapid Review Series is formatted as a bulleted outline with photographs, tables, and figures that address all the pharmacology information you need to know for the USMLE. And with Student Consult functionality, you can become familiar with the look and feel of the actual exam by taking a timed online test that includes more than 450 USMLE-style practice questions. Review all the information you need to know quickly and easily with a user-friendly, two-color outline format that includes High-Yield Margin Notes. Take a timed online test at www.studentconsult.com with more than 450 USMLE-style questions and full rationales for why every possible answer is right or wrong. Access the most current information with completely updated chapters, images, and questions. Profit from the guidance of series editor, Dr. Edward Goljan, a well-known author of medical study references, who is personally involved in content review. Easily review all essential information with new drug tables that detail mechanism of action, clinical uses, and adverse reactions. Study and take notes more easily with the new, larger page size. Practice with a new testing platform on USMLE Consult that gives you a realistic review experience and fully prepares you for the exam. Learn the "must know" pharmacology information needed to succeed on the USMLE

This book addresses the highly relevant and complex subject of research on drugs from natural products, discussing the current hot topics in the field. It also provides a detailed overview of the strategies used to research and develop these drugs. Respected experts explore issues involved in the production chain and when looking for new medicinal agents, including aspects such as therapeutic potential, functional foods, ethnopharmacology, metabolomics, virtual screening and regulatory scenarios. Further, the book describes strategic methods of isolation and characterization of active principles, biological assays, biotechnology of plants, synthesis, clinical trials and the use of tools to identity active principles.