This book reviews recent breakthroughs in anti-cancer drug discovery. Building on the previous volume in the series, it outlines some of the most significant developments that have occurred in the field in the subsequent period that have led to new drug approvals or promising clinical candidates. The volume is divided into chapters that each relate to a specific protein or protein class. Each chapter provides an overview of the underlying biology and then emphasises the medicinal chemistry strategies and tactics that led to the most significant drugs and drug candidates. A summary of clinical data and the future outlook for the field is also provided. Each chapter is authored by experts in the topic and who have themselves made significant contributions to their respective fields.

This title is a comprehensive text that addresses key aspects of nanomedicine such as properties occurring at the nanoscale that have unique medical effects, great molecular knowledge of the human body and disease processes, and apparent clinical translation as opposed to narrow insufficient texts that address only a few topics and attempt to "rebrand" established drug delivery. It will clearly define the field which is needed due to the immaturity and broad nature of the field. The book is aligned with both the USA and European roadmaps for nanomedicine and will address initiatives taken in Asia that ensures timely and relevant content. In-depth chapters ensure each section is adequately covered. The nanopharmaceutical section focuses on novel drug delivery systems relevant to nanomedicine and the book has an extensive section on immune recognition at the nanoscale which has implications for in vivo applications of nanomedicines.

"Molecular Pharmacognosy" discusses the application of molecular biology in resource science and authentication of traditional Chinese medicine (TCM). This book reviews the latest developments in pharmacognosy, introduces a series of new views and insights, presents the hotspots and focus of the field of study on molecular pharmacognosy, and predicts a new direction of study on the resource science of TCM. Furthermore, the book also provides an open communications platform for the development of molecular pharmacognosy. This book is intended for biomedical scientists and researchers in the fields of molecular biology, traditional medicine and natural pharmaceutics.

Professor Lu-qi Huang is Director of the Collaborating Centre of the World Health Organization for Traditional Medicine (Chinese Materia Medica) and Vice-Chairman of the Australia Chinese Association for Biomedical Sciences Inc.

This volume provides state-of-the-art and novel methods on antibiotic isolation and purification, identification of antimicrobial killing mechanisms, and methods for the analysis and detection of microbial adaptation strategies. Antibiotics: Methods and Protocols guides readers through chapters on production and design, mode of action, and response and susceptibility. Written in the highly successful Methods in Molecular Biology series 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 cutting-edge, Antibiotics: Methods and Protocols aims to inspire scientific work in the exciting field of antibiotic research.

'It is indeed the merit of Dr. Alan F. Casy to bring in these pages a clear and comprehensive view of medicinal stereochemistry, a discipline in which he has been active and successful for many years both as a teacher and a researcher. Written for graduate students and research workers in medicinal chemistry and pharmacology, this book will contribute significantly towards a better education of scientists by removing the fear of stereochemistry caused by ignorance, moderating the overconfidence of possible zealots, and outlining a broader context.'-from the foreword by Bernard Testa

This comprehensive volume focuses on anti-inflammatory nutraceuticals and their role in various chronic diseases. Food and Drug Administration (FDA) approved drugs such as steroids, non-steroidal anti-inflammatory drugs (NSAIDS), statins and metformin have been shown to modulate inflammatory pathways, but their long-term intake has been associated with numerous side effects. This means that there is enormous potential for dietary agents that can modulate inflammatory pathways in humans. Leading experts describe the latest research on the role of anti-inflammatory nutraceuticals in preventing and treating chronic diseases.

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

Ready to master the medication process? Tap into the go-to resource for nursing pharmacology basics, with the fully updated new fifth edition of Pharmacology Made Incredibly Easy! (R). Offering clear, concise descriptions of crucial nursing pharmacology concepts and procedures, this easy-to-follow, colorfully illustrated guide offers step-by-step guidance so to can grasp the fundamentals in enjoyable Incredibly Easy style. From initial assessment to safe medication administration and patient care plans, this is the perfect supplement to class materials, offering solid preparation for NCLEX (R), as well as a handy refresher for experienced nurses. Learn the ins and outs of nursing pharmacology care, with the latest data and protocols: NEW chapters on patient education, sensory drugs, and dermatologic drugs NEW chapter on medication safety, including abbreviations to avoid and a review of dosage calculations NEW content on current approved medications and dosages, and expected versus adverse effects NEW content on emergency drugs, herbs/supplements, immunization schedule, and more Hundreds of colorful diagrams, drawings, and charts that illustrate core concepts, with easy-to-retain definitions and clear direction on administering drugs; drug distribution, absorption, and metabolism; drug classes and their uses; and potential drug interactions Quick-scan outline format offers up-to-date guidance on areas including: Nursing pharmacology fundamentals Concepts of pharmacokinetics, pharmacodynamics, and pharmacotherapeutics Pain drugs, autonomic nervous system drugs, neurologic and neuromuscular drugs Psychotherapeutic, anti-infective, anti-inflammatory, anti-allergy, and immunosuppressant drugs Antineoplastic drugs, drugs for fluid and electrolyte balance Ways a drug may affect patients of different ages and other warnings Content reflects the NCSBN Clinical Judgment Measurement Model - guidance from initial assessment to evaluating outcomes "Practice Makes Perfect" end-of-book practice exam - approximately 100 new NCLEX (R)-style questions, to increase your exam confidence Chapter features include: Prototype pro - Actions, indications, and nursing considerations for common prototype drugs A three-step process is provided throughout the chapters to help you care for individuals taking commonly prescribed medications Pharm function - Explains and illustrates how drugs act in the body, and addresses how to recognize and treat adverse reactions Before you give that drug - Warnings to consider before you administer a drug Education edge - Information to share with your patient Black Box Warnings boxes draw attention to life-threatening concerns Lifespan Lightbulb boxes highlight information about how a drug or drug class may affect patients of different ages Quick quiz - End-of-chapter questions with answers/explanations, to help you remember the essentials Nurse Joy and Jake illustrated characters offer tips and insights throughout About the Clinical Editors Cherie R. Rebar, PhD, MBA, RN, CNE, CNECI, COI, FAADN, is a Professor of Nursing at Wittenberg University in Springfield, Ohio Nicole Heimgartner, DNP, MSN, RN, CNE, CNECI, COI, is a Nursing Faculty member at Galen College of Nursing in Louisville, Kentucky Carolyn Gersch, PhD, MSN, RN, CNE, is a Professor of Practice in the Nursing Program at Wittenberg University in Springfield, Ohio

t Heinz Red! and Gunther Sch!ag Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria The word "sepsis" derives from the Greek meaning decay or rottenness. Tradition ally this term has been used to describe the process of infection accompanied by the host's systemic inflammatory response. Based on that understanding, previous clin ical studies have been designed to include only patients with positive blood cultures [1, 2]. However, the frequent occurrence of a septic response without the demon stration of microorganisms in the circulation has led to a new definition and under standing of sepsis, mainly as the systemic response of the host to an often unde tectable microbiological or non-microbiological process [3]. The general consensus is that cytokines are central to the inflammatory response, particularly in sepsis. It is now known that not only Gram-negative but also Gram positive, viral, and fungal infections initiate the complex cascades of cytokine release. Probably the most important aspect of bacterial action is the release of toxic bacterial products. In particular endotoxin from Gram-negative bacteria (see chap ter by Schade) and super antigens (see chapter by Neumann and Holzmann), as well as pore-forming toxins [4] from Gram-positive bacteria, induce cytokine formation. The importance of this cytokine release is evident from both diagnostic and thera peutic (mostly experimental) studies, and the action of cytokines may be the key to our understanding of the pathophysiology of the sepsis syndrome.

Thoroughly revised and updated, "Optimization in Drug Discovery: In Vitro Methods, Second Edition" presents a wide spectrum of in vitro assays including formulation, plasma binding, absorption and permeability, cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) metabolism, CYP inhibition and induction, drug transporters, drug-drug interactions via assessment of reactive metabolites, genotoxicity, and chemical and photo-mutagenicity assays. Written for the "Methods in Pharmacology and Toxicology" series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Expert authors have developed and utilized these in vitro assays to achieve drug-like characteristics in addition to efficacy properties and good safety profiles of drug candidates.

Comprehensive and up-to-date, "Optimization in Drug Discovery: In Vitro Methods, Second Edition" aims to guide researchers down the difficult path to successful drug discovery and development."

Each chapter of this volume is a contribution from an expert in the field, chosen by the editors to contribute to the 1997 "Current Issues in Blood Substitute Research and Development" course given in San Diego, March 17-19. The contributors were selected because of their expertise in areas which the editors believe to be critical to the advancement of the field, and which reflect activity in "hot" areas of relevant research. While there is a continuity in style for the annual course, each year brings changes in emphasis and content. In previous years, we were often not able to provide time for participants to present their views and opinions. Consequently, this year we encouraged discussion after each presentation. These sessions were recorded, transcribed, and are printed with the chapters herein. We believe that the product is very close to the capturing this year's course in print, and trust readers will enjoy reading the always candid and often provocative remarks from the audience. The price paid for inclusion of the discussion transcriptions was a delay in publication. Each author was allowed to edit his/her discussion section as well as the final version of the chapters prior to publication. The changes are mainly for grammar, and we tried, when possible, not to alter the conversational style of these interchanges.

Infectious diseases caused by viruses, parasites, bacteria, and fungi are the number one cause of death worldwide. Although new technologies have improved diagnosis of infectious diseases, the efficacy of all known current anti-infective agents is threatened by the spread of drug-resistant forms of the pathogens. Hence, there remains an urgent need to develop anti-infective agents that target drug-resistant pathogens. In Silico Models for Drug Discovery presents a comprehensive look at the role in silico models play in understanding infectious diseases and in developing novel therapeutics to treat them. Written by leading experts in the field, chapters cover topics such as techniques to derive novel antimicrobial targets, methods of interpreting polypharmacology-based drug target networks, and molecular dynamics techniques used to compute binding energies of drugs to their target proteins, to name a few. Written in the successful Methods in Molecular Biology (TM) series or in review article format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, In Silico Models for Drug Discovery seeks to serve both professionals and novices involved in the study and treatment of infectious diseases.

Sodium channels confer excitability on neurons in nociceptive pathways and exhibit neuronal tissue specific and injury regulated expression. This volume provides recent insights into the control of expression, functioning and membrane trafficking of nervous system sodium channels and reviews why sodium channel sub-types are potentially important drug targets in the treatment of pain. The roles of sodium channels in dental and visceral pain are also addressed. The emerging role of sodium channel Nav1.3 in neuropathic states is another important theme.

Authors from the pharmaceutical industry discuss pharmacological approaches to the drug targeting of sodium channels, and in particular Nav1.8, exclusively expressed in nociceptive neurons. The final chapter highlights the functional diversity of sodium channels in part provided by post-transcriptional processing and the insights into sodium channel function that are being provided by tissue specific and inducible gene knock-out technology.

The last decade has seen a renaissance of the concept of individualized chemotherapy in oncology, markedly stimulated by the development of new in vitro chemosensitivity assays. The clinical utility of drug response assays has been evaluated in clinical trials and the results suggest that assay-assisted therapy selection may improve survival as well as economic outcomes. This volume comprises the proceedings of the first Symposium of the International Society for Chemosensitivity Testing in Oncology, ISCO-1, held in Homburg/Saar, Germany, in September 2001. The topics include: new in vitro drug-testing methods, tumor chemosensitivity assays, and the clinical relevance of assay-directed therapy.

This work stems from the activities carried out under the European Science Foundation's Environmental Toxicology Programme and its daughter programme, Environmental Damage and its Assessment. The work served also as a pilot study for the ESF Scientific programme on Environment, Science and Society (ESS), thus demonstrating the interdependence of the natural and social sciences with respect to environmental issues. The book is unique in the sense that it records the results of a four year collaboration between environmental toxicologists, economists and institutionalists. Its objective was to achieve better characterized or even novel insights into the theory and practice of water resource management, quality assurance and chemical safety regulation.

The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.

An in-depth exploration of the applications of plant bioactive metabolites in drug research and development

Highlighting the complexity and applications of plant bioactive metabolites in organic and medicinal chemistry, "Plant Bioactives and Drug Discovery: Principles, Practice, and Perspectives" provides an in-depth overview of the ways in which plants can inform drug research and development. An edited volume featuring multidisciplinary international contributions from acclaimed scientists researching bioactive natural products, the book provides an incisive overview of one of the most important topics in pharmaceutical studies today.

With coverage of strategic methods of natural compound isolation, structural manipulation, natural products in clinical trials, quality control, and more, and featuring case studies on medicinal plants, the book serves as a definitive guide to the field of plant biodiversity as it relates to medicine. In addition, chapters on using natural products as drugs that target specific disease areas, including neurological disorders, inflammation, infectious diseases, and cancer, illustrate the myriad possibilities for therapeutic applications.

Wide ranging and comprehensive, "Plant Bioactives and Drug Discovery" also includes important information on marketing, regulations, intellectual property rights, and academic-industry collaboration as they relate to plant-based drug research, making it an essential resource for advanced students and academic and industry professionals working in biochemical, pharmaceutical, and related fields.

After the successful introduction of acupuncture to the West, recent advances in analytical methods in chemistry, molecular biology and systems biology especially the development of the omic technologies have again brought Chinese drugs into the focus of research on Traditional Chinese Medicine (TCM). With more than 1000 publications on the chemistry, molecular biology and pharmacology of TCM drugs in international journals over the last 10 years, Chinese drugs are gaining increasingly reputation and impact. These data offer great opportunities for the development of new pharmaceuticals for various clinical applications. International scientists have compiled relevant and trend setting research results in this book. Topics range from the latest methods of quality and safety assurance by chemical and genetic fingerprints to the development of new pharmaceuticals for a future evidence-based therapy e.g. for cancer, cardiovascular, inflammatory or infectious diseases as well as to recent experimental results on multitarget and synergy research for the preparation of multi-extract-pharmaceuticals from TCM.

Medicine has entered a golden age in which therapeutic agents are becoming widely available due to advances in basic science and technology. As such, many drugs have been developed that target inflammatory processes and/or the immune system. This book is intended for health professionals examining the modulation of inflammation by immunotherapeutic drugs. The immune system fills the primordial role of host defense and resistance to infections with pathogenic microorganisms. Several hematopoietic-derived cells constituting the innate and adaptive immune systems cooperate to provide barriers for microbial colonization and/or promote pathogen destruction within the host. Conversely, many immune cells are also involved in the pathogenesis and propagation of chronic inflammatory diseases. The beginning of this book details various components of the immune system including the cell types, lymphoid tissues, soluble cytokines and surface molecules that are essential for host defense. Breakdowns in immune tolerance, or dysregulated immune responses to antigens derived from self tissues or innocuous sources, can lead to the development of autoimmunity or chronic inflammatory diseases. Pathophysiologic roles for the immune system are detailed in corresponding chapters on autoimmunity, epithelial surfaces (lungs, skin, intestine), and transplantation, with special emphasis placed on immunotherapeutic drug targets. The last section of the book focuses on treatments that stimulate our immune system to specifically target and fight infectious diseases and cancer. In each chapter, the medications used to treat various diseases/conditions in terms of their mechanism of action and other pharmacologic properties are detailed. Chapters begin with a table showing drug names and classifications. The importance of basic science and clinical trials cannot be understated in the context of drug development. As such, the discovery of certain medications that had a lasting impact in medicine and pharmacy are highlighted in chapter subsections named "Bench to Bedside." Several clinical applications of immunotherapeutic drugs are described within end-of -chapter case studies including practice questions. The Pharmacology of Immunotherapeutic Drugs is a reference for immunologists and clinicians (medical doctors, pharmacists, nurses) examining the modulation of inflammatory processes by a variety of medications targeting the cells and mediators of our immune system.

This volume explores the considerable efforts that have been directed towards the development of G Protein-Coupled Receptors (GPCR) screening assays in order to disclose GPCR acting compounds, elucidate signaling mechanisms or evaluate compound's efficacy. New discoveries in the field, along with the widely recognized need for better and safer pharmaceutical drugs constitute the main motivation for this book. Readers, both beginners and experienced researchers, will receive an updated overview of not only the established, but also the innovative technologies that promise to advance GPCR drug research. This book is organized into two major parts: the introductory part discusses the necessary foundations for the understanding of GPCR action and the rationale behind the design of the available screening assays; and part two provides detailed protocols for different screening approaches. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Practical and innovative, G Protein-Coupled Receptor Screening Assays: Methods and Protocols reaches out to everyone involved in the discovery of GPCR-active drugs, and provides a transversal overview of the different levels of GPCR signaling addressable in the different screening strategies and presents practical examples of how current assay technologies are contributing to new paradigms in GPCR drug research.

Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. In Antibody-Drug Conjugates, expert researchers provide detailed protocols for many of the key ADC techniques necessary for working in the field. These chapters and methodologies are aimed at the key tasks necessary to identify a suitable target, properly design the mAb, the linker and the payload, as well as to conjugate them in a reproducible and scalable fashion. Written in the highly successful Methods in Molecular Biology (TM) format, these detailed chapters include the kind of practical implementation advice that guarantees quality results. Authoritative and timely, Antibody-Drug Conjugates aims to further drive ADC development and thus help toward improving cancer treatments of the future.

The purpose of Applications Therapeutic of Ribozymes is to provide an overview of the utility of ribozymes to selectively inhibit the expression of RNA. The ribozyme applications appearing in this book should benefit not only those experienced in ribozymes, but also those applying this ribozyme technology for the first time. It is hoped that a better understanding of the therapeutic application ofribozymes will have a significant impact on human disease in the near future. The field ofribozyme biochemistry has come a long way since the initial observation that RNA is capable of catalysis, initially in cis during processing of larger molecules and ultimately the use of ribozymes in trans to achieve cleavage of target sequence. The fundamental observation that hammerhead (and subsequently hairpin) ribozymes could be designed to cleave a target messenger RNA, and the clarification of sequence restrictions in both the ribozyme and the target RNA, have paved the ways for the use of ribozymes as a tool to manipulate gene expression at the molecular level. This had pre- ously been a domain of antisense oligonucleotides and triplex DNA. Sub- quent studies have explored the myriad biological systems in which ribozyme-mediated inhibition of genes involved in various cellular processes may be used to uncouple important signaling pathways or to reverse the p- notypic expression of a pathologic process.