Following the success of the first edition, this pioneering study of pharmaceuticals in the environment has been updated and greatly extended. It includes the status of research on pharmaceuticals in soil, with attention to terrestrial and aquatic environments as well as new substance categories such as tetracylines and chinolones and the latest results concerning contamination of the environment and risk reduction.

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

Efforts to describe and model the molecular structure of biological membranes go back to the beginning of the last century. In 1917, Langmuir described membranes as a layer of lipids one molecule thick [1]. Eight years later, Gorter and Grendel concluded from their studies that "the phospholipid molecules that formed the cell membrane were arranged in two layers to form a lipid bilayer" [2]. Danielli and Robertson proposed, in 1935, a model in which the bilayer of lipids is sequestered between two monolayers of unfolded proteins [3], and the currently still accepted fuid mosaic model was proposed by Singer and Nicolson in 1972 [4]. Among those landmarks of biomembrane history, a serendipitous observation made by Alex Bangham during the early 1960s deserves undoubtedly a special place. His fnding that exposure of dry phospholipids to an excess of water gives rise to lamellar structures [5] has opened versatile experimental access to studying the biophysics and biochemistry of biological phospholipid membranes. Although during the following 4 decades biological membrane models have grown in complexity and functionality [6], liposomes are, besides supported bilayers, membrane nanodiscs, and hybrid membranes, still an indisputably important tool for membrane b- physicists and biochemists. In vol. II of this book, the reader will fnd detailed methods for the use of liposomes in studying a variety of biochemical and biophysical membrane phenomena concomitant with chapters describing a great palette of state-of-the-art analytical technologies.

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.

This series ofbooks on the biotechnology of Medicinal and Aromatic Plants provides a survey of the literature focusing on recent information and the state of the art in tissue culture and the in vitro production of secondary metabolites. This book, Medicinal and Aromatic Plants VIII, like the previous seven volumes published in 1988, 1989, 1991, 1993, and 1994, is unique in its approach. It comprises 26 chapters dealing with the distribution, importance, conventional propagation, micropropagation, tissue culture studies and the in vitro production of important medicinal and pharmaceutical compounds in various species of Achillea, Anethum, Aquilaria, Arnica, Aspergillus, Astragalus, Catalpa, Chelidonium, Eremo phila, Eucalyptus, Eucommia, Geranium, Heterocentron, Hypericum, Maclura, Morinda, Mortierella, Nicotiana, Phaseolus, Pinellia, Piqueria, Psorales, Rhodiola, Sanguisorba, Valeriana, and Vancouveria. This book is tailored to the needs of advanced students, teachers, and research scientists in the field of pharmacy, plant tissue culture, phytochemistry, biochemical engineering, and plant biotechnology in general. New Delhi, July 1995 Professor Y. P. S. BAJAJ Series Editor Contents I Achillea millefolium L. ssp. millefolium (Yarrow): In Vitro Culture and Production of Essential Oils A. C. FIGUEIREDO, M. S. S. PAIS, and J. J. c. SCHEFFER (With 9 Figures) 1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 In Vitro Culture Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3 Ultrastructural Study of the Glandular Trichomes and Cell Suspension Cultures . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 4 Composition of the Essential Oils of A. millefolium In Vivo and In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 5 Summary and Conc1usion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 6 Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 II Anethum graveolens L."

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. "

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.

The only comprehensive work to cover all aspects of diuretic agents, the book discusses the pharmacology and toxicology of diuretic agents as well as the physiological effects. Experts in the field present the principles and experimental approaches for the study of interactions between pharmacologic compounds in relation to specific target organs. Diuretic Agents contains information on the mechanisms of action and application of diuretics, and details FDA regulations and pharmaceutical industry guidelines.
Key Features
* Written by experts in the field
* Covers all aspects of diuretic agents
* Includes information on the mechanisms of action and application of diuretics

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.

The layout of the book is simple, attractive and reader-friendly - it is a unique blend of basic and fundamental aspects of pharmacovigilance. Contains a dedicated chapter of 100 Case Studies with answers for hand-on training and experience in Pharmacovigilance practices. Key points are given in the initial page of every chapter for chapter overview. Sample Model Papers comprising of MCQs, Case Study, Long and Short Answer questions have been given at the end of the book to prepare students for exams. Enriched with lots of flowcharts, tables and line diagrams for making learning easy and interesting. Includes a glossary of terminologies used in the text in the beginning of the book with useful abbreviations. References for further reading are provided at the end of each chapter. Exhaustive appendices on different reporting forms of various countries. Good guide for medical, clinical research and pharmacovigilance students and other healthcare professionals.

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 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.

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 is a short and simple pedagogical guide to the diagnosis and management of epilepsy. After the headache, epilepsy is the second most common neurological disorder, and this book clarifies the many courses of action to take in treating patients with epilepsy. The book simplifies the classification, testing, and treatment of epilepsy, addresses important psychosocial issues and the efficacy of pharmaceutical and other interventions, and also includes an account of modern concepts of the aetiology of the disease. The Comprehensive Evaluation and Treatment of Epilepsy: A Practical Guide is an important reference work for all medical schools, hospitals, clinics and primary care centers. Features: * CONTAINS ESSENTIALS ON: * Initial management of patients with seizures * Psychosocial aspects of epilepsy * Neuropsychologic problems associated with epilepsy * Psychiatric disorders * Diagnosis and treatment of status epilepticus * Nonepileptic seizures * Ambulatory EEG monitoring * Epilepsy surgery * Endocrine aspects of partial seizures * Epilepsy in the elderly

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."

Drug-Drug Interactions is a comprehensive review of the scientific and regulatory perspectives of drug-drug interactions from the point-of-view of academia, industry, and government regulatory agencies. This book is intended for professionals in the pharmaceutical industry, health care, and governmental regulatory agencies. Topics of interest include the mechanistic understanding of drug-drug interactions, the prediction of drug-drug interaction potential of new drugs, and the avoidance of clinically significant drug-drug interaction in patients.
Key Features
* Provides useful references on the science of drug-drug interactions
* Describes in a basic and comprehensive manner drug-drug interactions from the mechanistic viewpoint
* Contains original data from academic and industrial laboratories
* Presents an overview of regulatory agency positions

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.

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.

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.

Specially designed computer software is revolutionizing procedures for structured or rational drug design and discovery. The Guidebook on Molecular Modeling in Drug Design serves as a manual for the analysis ofmolecular structure and the correlation of these structures with pharmacological reactions. Intended as an introductory guide for advanced students and professionals with an interest in computer-assisted modeling for drug design and discovery, this bookwill also be of interest to medicinal and organic chemists, pharmaceutical researchers, pharmacologists, and biochemists who want to gain further insight into this rapidly advancing field.
Molecular modeling is assuming an important role in the understanding of three-dimensional aspects in the specificity of drug-receptor interactions at the molecular level. This research area has become a well-established discipline in pharmaceutical research. It has created unprecedented opportunities in assisting medicinal chemists in the design of new therapeutic agents. Advances made in computer hardware and in theoretical medicinal chemistry have brought high-performance computing and graphics tools within reach of most academic and industrial laboratories, facilitating the development of useful approaches to rational drug design.
The Guidebook on Molecular Modeling in Drug Design serves as a manual for the analysis of the molecular structure of biological molecules and drugs and the correlation of these structures with pharmacological actions. Intended as a guide for advanced students and professionals with an interest in computer-assisted modeling for drug design and discovery, this book will also be of interest to medicinal and organic chemists, pharmaceutical researchers, pharmacologists, and biochemists who want to gain further insight into this rapidly advancing field.

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 90 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.

''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

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.

Neuropeptide Y (NPY) is a ubiquitous and important messenger in the nervous system, with a wide range of physiological roles. It is involved in the body energy balance and is one of the most potent stimuli of food intake known. NPY also acts to regulate central and peripheral autonomic functions.
This book, written by academic and industrial experts in the field, links the most recent basic experimental knowledge about NPY and its receptors with areas of clinical importance.
This book will be of interest to those working in all areas of research affected by NPY, such as food intake and energy homeostasis, cardiovascular regulation and G-protein-coupled receptors, as well as those interested in the development of drugs as NPY targets.
Key Features
* The hypothalamic role of NPY and its relationship with eating disorders and diabetes
* The sympathetic nervous system role of NPY and its involvement in cardiovascular disorders
* Characterization of NPY receptor types and their brain distribution, molecular biology and pharmacology
* Development of peptide and non-peptide receptor antagonists