Contents. List of Contributors. Brian Henderson and Gerry Higgs: Targets for modulating cytokine responses in inflammatory and infectious diseases. Mary Lee MacKichan and Anthony L. DeFranco: Cell signalling and cytokine induction by lipopolysaccharide. Rodger A. Allen and Stephen E. Rapecki: Regulation of cytokine production by inhibitors of cell signalling. Stanley T. Crooke: Oligonucleotide-based drugs in the control of cytokine synthesis. Peter I. Croucher, Ingunn Holen and Philip G. Hargreaves: Inhibiting cytokine-processing enzymes. Amanda Suitters and Roly Foulkes: Cytokine-neutralizing therapeutic antibodies. Ravinder N. Maini: The debut of anti-TNF therapy of rheumatoid arthritis in the clinic. Anthony Meager: Blockade of cytokine activity by soluble cytokine receptors. Michael F. Smith Jr.: Interleukin-1 receptor antagonist. Raymond J. Owens and Simon Lumb: Therapeutic regulation of cytokine signalling by inhibitors of p38 mitogen-activated protein kinase. Christian Bogdan, Yoram Vodovotz and John Letterio: TGF-ss and IL-10: inhibitory cytokines regulating immunity and the response to infection. Brian Henderson: Therapeutic control of cytokines: lessons from microorganisms. Index

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

As the number of people aged 65 years and above rises, physicians are increasingly confronted by elderly patients with impaired renal function, altered drug metabolism and multiple comorbidities. This book examines in detail the nature of renal injury in the elderly and its optimal management. A wide range of key topics are covered, including end-stage renal disease, diabetic nephropathy, acute kidney injury, drug metabolism and renal toxicity, dialysis and its complications and the use of renal transplantation. In addition, the assessment of glomerular filtration rate in the elderly and the role of novel renal biomarkers are carefully examined. Quality of life issues, the significance of other age-related medical problems and end of life care are also discussed. This book will be of value not only to nephrologists but also to general practitioners, medical students, intensivists, cardiologists, pharmacologists and those working in related specialties. "

Toxicity Assessment Alternatives: Methods, Issues, Opportunities contains a broad array of critical surveys, contributed by active and respected investigators, describing their research and offering updates on toxicity assessment alternatives, directions determined by current and future grant programs, opportunities for mechanistically based test methods to detect endocrine disruptor activity, the use of alternatives in the Department of Defense hazard assessment initiatives, and the issues and opportunities for validation and regulatory acceptance. Several of these advances make use oftransgenic models that reduce the time and cost of carcinogenicity testing. Others use tissue cultures for the assessment of endocrine disrupting chemicals. Cultures of human epidermal keratinocytes are applicable as models for sulfur mustard lesions, and in vitro protein denaturation is used as a chemical test for assessing the ocular and dermal irritation potential of cosmetic prod ucts. Molecular modeling is applied to explaining chemical toxicity. Commercially developed assay systems have undergone extensive evaluation by their manufacturers. Some of these await external valida tion, and others await acceptance by North American and European regulatory agencies. Toxicity Assessment Alternatives: Methods, Issues, Opportunities provides information from members of the scientific and regulatory communities on what has been achieved and what has been accepted in alternatives to animal testing."

The tetracyclines have an illustrious history as therapeutic agents which dates back over half a century. Initially discovered as an antibiotic in 1947, the four ringed molecule has captured the fancy of chemists and biologists over the ensuing decades. Of further interest, as described in the chapter by George Armelagos, tetracyclines were already part of earlier cultures, 1500-1700 years ago, as revealed in traces of drug found in Sudanese Nubian mummies. The diversity of chapters which this book presents to the reader should illus trate the many disciplines which have examined and seen benefits from these fascinating natural molecules. From antibacterial to anti-inflammatory to anti autoimmunity to gene regulation, tetracyclines have been modified and redesigned for various novel properties. Some have called this molecule a biol ogist's dream because of its versatility, but others have seen it as a chemist's nightmare because of the synthetic chemistry challenges and "chameleon-like" properties (see the chapter by S. Schneider).

This book provides in-depth information on the applications of cannabis products as a legitimate medicine in treating a variety of diseases and disorders in domestic animals. Pharmacology and toxicology of cannabinoids and their effects on the endocannabinoid system, which is involved in the regulation of diverse physiological and cognitive processes, are discussed in detail. Furthermore, the book reviews development and testing of cannabis based medical products and introduces the nutritional components of cannabis plants. Cannabis as a therapeutic in veterinary medicine is gaining interest among owners and practitioners. Numerous studies have been completed or are currently underway that analyze the potential of clinical application of cannabinoid and terpenoid molecules. In this book the authors take a comprehensive look at previous studies in animal and human models and discuss translational applications based on these scientific data. This seminal text serves as a go-to resource for veterinary practitioners on cannabinoid therapy. It will also serve as a foundation for clinicians and researchers interested in this emerging field of veterinary medicine.

This book offers a comprehensive but highly readable compilation of papers on the role of dopamine in sleep and sleep disorders. Leading experts in sleep medicine, psychiatry and neuroendocrinology provide a broad perspective on the field, from established theories to the latest research advances. Accordingly, it represents an interdisciplinary, cutting-edge guide for sleep disorder specialists, sleep researchers, psychiatrists, neurologists, pulmonologists, psychologists, and behavioral sleep medicine specialists.

The mechanisms and physiological functions of urea transporters across biological membranes are subjects of long-standing interests. Although urea represents roughly 40% of all urinary solutes in normal human urine, the handling of urea in the tissues has been largely neglected in the past and few clinical or experimental studies now report data on urea. Most recent physiological text books include chapters on water and electrolyte physiology but no chapter on urea. Our aim in writing this book is to stimulate further research in new directions by providing novel and provocative insights into the further mechanisms and physiological significance of urea metabolism and transport in mammals. This book offers a state-of-the-art report on recent discoveries concerning urea transport and where the field is going. It mainly focuses on advances made over the past 20 years on the biophysics, genetics, protein structure, molecular biology, physiology, pathophysiology and pharmacology of urea transport in mammalian cell membranes. It will help graduate students and researchers to get an overall picture of mammalian urea transporters and may also yield benefits for pharmaceutical companies with regard to drug discovery based on the urea transporter. Baoxue Yang is a professor and vice chairman of the Department of Pharmacology, Peking University. He is also an adjunct professor of Jilin University and a visiting professor of Northeast Normal University. Prof. Yang has been researching urea transporters for nearly 20 years and has published more than 70 original research articles in this field.

Mycotoxins, from the Greek "mukes" referring to fungi or slime molds and toxin from the Latin "toxicum" referencing a poison for arrows, have earned their reputation for being potentially deleterious to the health and well being of a consuming organism, whether it be animal or human. Unfortunately, mycotoxins are a ubiquitous factor in the natural life cycle of food producing plants. As such, control of the potential impact of mycotoxins on food safety relies heavily upon accurate analysis and surveys followed by commodity segregation and restricted use or decontamination through processing. The purpose of this book is to provide the most comprehensive and current information on the topic of mycotoxins and assuring food safety. Chapters represented in the book reflect such diverse topics ranging from occurrence and impact, analysis, reduction through processing and plant breeding, toxicology and safety assessments to regulatory perspectives. Authors represent a range of international perspectives.

Rapid advances in computer science, biology, chemistry, and other disciplines are enabling powerful new computational tools and models for toxicology and pharmacology. These computational tools hold tremendous promise for advancing science, from streamlining drug efficacy and safety testing, to increasing the efficiency and effectiveness of risk assessment for environmental chemicals. Computational Toxicology provides biomedical and quantitative scientists with essential background, context, examples, useful tips, and an overview of current developments in the field. Divided into four sections, Volume I covers a wide array of methodologies and topics. Opening with an introduction to the field of computational toxicology and its current and potential applications, the volume continues with 'best practices' in mathematical and computational modeling, followed by chemoinformatics and the use of computational techniques and databases to predict chemical properties and toxicity, as well as an overview of molecular dynamics. The final section is a compilation of the key elements and main approaches used in pharmacokinetic and pharmacodynamic modeling, including the modeling of absorption, compartment and non-compartmental modeling, physiologically based pharmacokinetic modeling, interspecies extrapolation, and population effects. Written in the successful Methods in Molecular Biology (TM) series format where possible, chapters include introductions to their respective topics, lists of the materials and software tools used, methods, and notes on troubleshooting. Authoritative and easily accessible, Computational Toxicology will allow motivated readers to participate in this exciting field and undertake a diversity of realistic problems of interest.

''A wealth of information...these two volumes will be immensely valuable to anyone having to deal with this difficult group of compounds.'' ---Biochemical Systematics and Ecology, from a review of Saponins Used in Traditional and Modern Medicine and Saponins Used in Food and Agriculture

Annual Reports in Medicinal Chemistry, Volume 57 in this long-running series, highlights new advances in the field with this new volume presenting interesting chapters on the Mechanism of action of the broadly acting antiviral drug remdesivir, Improving properties of the nucleobase analogue T-706 as a potential anti-SARS-CoV-2 and anti-influenza compound, Antivirals for RNA virus infections Anno 2020-2021, Broad spectrum antiviral fleximer nucleosides, SARS-CoV-2 main protease inhibitors, The search for antivirals to treat alphavirus infections, Inhibitors of Ebola Virus targeting Innate immune evasion, Uracil derivatives as non-nucleoside inhibitors of viral infections, and more.

Conceptually unsavoury, airway mucus is vital to homeostasis in the respiratory tract. In contrast, when abnormal, mucus contributes significantly to the pathophysiology of a number of severe bronchial diseases, including asthma, chronic bronchitis and cystic fibrosis. This volume provides wide ranging and in-depth coverage of the scientific and clinical aspects of airway mucus. It commences with introductory chapters which address the biochemical and molecular biological basis of airway mucus and continues with comprehensive coverage of the various physiological and rheological aspects of respiratory secretions. The clinical aspects of the topic are then considered, with chapters discussing the involvement of mucus secretions in bacterial infection and in hypersecretory diseases of the airway. The volume concludes with a discussion of the therapeutic aspects of the topic, both in terms of the possible approaches to the treatment of mucus hypersecretion and the interaction of these drugs with airway mucus. Written by leading experts in the field, each contribution provides a comprehensive review of its particular subject. Reflecting the latest advances in this important area of respiratory research, this volume will be of great interest to scientists and clinicians working in the field of airway secretions and related areas.

A comprehensive, state-of-the-art review of our current understanding of the molecular and structural biology of 5-HT receptors and their potential use for drug discovery. The authors describe the anatomical, cellular, and subcellular distribution of 5-HT receptors and demonstrate a powerful approach to elucidating their physiological role using knockout mice in which the 5-HT receptors were deleted. They also review our understanding of the physiological role(s) of 5-HT receptors based mainly on studies performed in genetically engineered mice. Highlights include discussions of the behavioral phenotypes of 5-HT receptor knockout animals, the molecular biology and pharmacology of 5-HT receptors, and insights into the complexity of 5-HT receptor signal transduction.

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

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

As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. 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 notes on troubleshooting and avoiding known pitfalls.

Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field."

380 years ago, in the year 1614, Ubbo Emmius transplanted the gene ofscience from Ostfriesland into the education genome ofthe city ofGroningen as devel oped by Regnerus Praedinius. He thereby founded the University ofGroningen. It is with great pleasure that the Faculty of Medicine as one of the founding faculties ofour University, welcomes you to this 19th International Symposium ofBloodTransfusion, whichwill coverthe themeofHereditaryDiseasesandtheir relation to Transfusion Medicine, where cell expansion, gene transfer and gene therapy are the read thread. Since the earlydays there has beena specificand sincere interest in inborn errors ofmetabolism and hereditarydisorders. This interest has resulted in a structured research, diagnostic and counselling facilities, and therapeuticapproaches where various disciplines within our faculty work closely together with groups from related faculties of the University of Groningen, as well as other national and international scientific institutions. The field of inborn errors, genetic abnormalities and mutations, and hereditary diseases covers a broad gamma of extremely interesting and exciting scientific aspects, whichrangefrom clearphysicalaberrationstomolecularanalysisofgenes and genomes, coding areas and amino acid sequences. It is intriguing to realise that the balance of life seemingly depends on the position or presence of one single molecule as a part ofthe total complex ofgenetic information in the cell."

Covering ocular pharmacokinetics, pharmacodynamics, and toxicology, Ocular Pharmacology and Toxicology provides ophthalmologists, toxicologists, and pharmacologists with both an introduction to the proper methods for ocular pharmacology and toxicology as well as providing practical methodologies for conducting ocular studies. Expert authors have contributed detailed chapters on study design, analysis, and routes to regulatory approval for various types and routes of ophthalmic drugs. As a volume in the Methods in Pharmacology and Toxicology series, chapters feature the kind of in-depth specifics and implementation advice to ensure successful results. Practical and authoritative, Ocular Pharmacology and Toxicology serves as an ideal basis of training in the proper design and conduct of essential studies to accurately determine pharmacokinetics and ocular toxicity from the systemic, topical, periocular, or intraocular administration of drugs or compounds, from the use of ocular medical devices and from ocular surgical procedures.

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics. While these products have certainly established recombinant biologics as a major pharmaceutical growth sector, the continued interest in this class of drugs arises from the fact that today we have a far better understanding of the human immune response, both at a cellular and molecular level. This has resulted in a more methodical characterisation of these factors which has given clinical researchers an opportunity to plan Phase 1 clinical trials that can provide substantial information on the activity of the cytokine in humans. Currently, a great deal of effort is also being channelled into identifying cytokines from the various DNA databases. Our major objective for this book is to profile cytokines that have been recently identified. The therapeutic potential of these cytokines based on their known properties will be discussed by the authors. The main aim of this book is to provide...

Role of Inflammation in Environmental Neurotoxicity, Volume Three, in this comprehensive serial, addresses contemporary advances in neurotoxicology by providing authoritative review articles on key issues in the field. Edited by leading subject experts, topics of note in this new release include Neuroinflammation (Introduction), Organophosphates, Lead, Manganese, Drugs of abuse, Peripheral vs central inflammation, Air pollution, Developmental neurotoxicity, Ethanol, and the Blood brain barrier, amongst other topics.