Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.

For this second edition of their much praised Cytochrome P450, the editors have collected accounts of the essential core techniques that use the latest methodologies for the investigation of P450s. Highlights include protocols for spectral analysis and purification of P450s, enzymatic assays of P450s and flavin-containing monooxygenases (FMOs), expression of P450s and FMOs in heterologous systems, and the production and use of antipeptide antibodies. Additional chapters contain readily reproducible techniques for the transfection of hepatocytes for gene regulation studies, P450 reporter gene assays, in situ hybridization, and analysis of genetic polymorphisms. Although the emphasis is on P450s of mammalian origin, many of the readily reproducible methods described are suitable for P450s from any source.

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABAA receptors underlie classical "phasic" GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.

Transfusion medicine is an excellent way for the healthy community to help the sick. However, service providers and patients have much to gain from the establishment of guidelines concerning when and how it is used. An important first step would be to introduce informed consent for transfusion recipients. Discussions with blood banks and assessment of clinical demand would also be necessary, taking into account the needs of patients and physicians, and the availability of products. Unfortunately, the efficacy and safety of transfusion products can be difficult to ascertain. Furthermore, although major advances have been made in safety, the risks of giving and receiving blood are still seen as high. It is vital to learn what underlies that perception and how to counter it. The policies and protocols used to establish surgical criteria for blood transfusions should be explored. Finally, clinical audits can help evaluate the risk: benefit ratio of transfusion; they may be carried out by hospital transfusion committees but are likely to be more successful with the support of national and international legislative and regulatory bodies. The implementation of appropriate initiatives now will improve the outlook for the future of transfusion medicine, perhaps with ex-vivo expanded haemopoietic cell therapy as the next milestone. All these key points and controversies are explored in this book, which paints a broad picture of the current status and future trends in transfusion medicine.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Artemisinin, a sesquiterpene lactone originally extracted from the medicinal plant Artemisia annua L., is an effective antimalarial agent, particularly for multi-drug resistant and cerebral malaria. However, the concentration of artemisinin in the plant is very low. Because the chemical synthesis of artemisinin is complicated and not economically feasible in view of the poor yield of the drug, the intact plant remains the only viable source of artemisinin production. Therefore, it is necessary to increase the concentration of artemisinin in A. annua to reduce the cost of artemisinin based antimalarial drugs. Plant scientists have focused their efforts on A. annua for a higher artemisinin crop yield. With the present volume, we are bringing together the research which is being done on this plant throughout the world and future possibilities for scientists and researchers who want to work on it.

Focused on the discovery of precise molecular targets for the development of the cancer preventive agents, "Cancer Prevention: Dietary Factors and Pharmacology" provides researchers and non-researchers with practical methodologies for developing and validating small molecule and phytochemical-derived drug discovery and mechanisms by which these compounds can modulate distinct target proteins involved in oncogenic signaling. While this volume is primarily focused toward cancer prevention research, the range of techniques demonstrated in the book also provides an introduction of cancer prevention research methods to researchers outside the field. Chapters deal with a critical discussion of both laboratory and clinical topics, with each chapter containing both a discursive section along with a detailed methods section. As part of the "Methods in Pharmacology and Toxicology" series, this meticulous volume includes the kind of key implementation advice that seeks to ensure successful results in the lab.

Practical and authoritative, "Cancer Prevention: Dietary Factors and Pharmacology" aims to guide research toward identifying molecular targets and conducting human studies with phytochemicals which would, ideally, provide an enhanced approach to the goal of personalized cancer prevention.

This volume explores the latest techniques used to investigate nanotoxicity. The protocols covered in this book range from routine nanotoxicity assays to genomic and proteomic approaches in vivo and in vitro. The chapters discuss specific topics such as preparation and utilization of 3D human liver microtissue models; assessment of ovarian granulosa cells with exposure to nanoparticles; DNA methylation analysis; evaluation of genotoxicity of nanoparticles in mouse models; and studying nanotoxicity using embryonic zebrafish. 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. Cutting-edge and practical, Nanotoxicity: Methods and Protocols is a valuable resource for researchers and postgraduate students in the fields of toxicology, environmental science, pharmacological sciences, and clinical medicine. This volume also serves as a starting point for researchers interested in learning more about this developing field.

This text offers state of the art contributions written by world renown experts which provide an extensive background on specific classes of antibiotics and summarize our understanding as to how these antibiotics might be optimally used in a clinical situation. The book explores pharmacodynamics methods for anti-infective agents, pharmacodynamics of antibacterial agents and non-antibacterial agents, as well as pharmacodynamic considerations and special populations. As part of the Methods in Pharmacology and Toxicology series, chapters include detailed insight and practical information for the lab. Comprehensive and cutting-edge, Antibiotic Pharmacodynamics serves as an ideal reference for scientists investigating advances in antibiotic pharmacodynamics now finding their way into the antibiotic development process used for licensing new antibiotics.

Radiophannaceutical research has recently undergone a major change in direction. In past years it has been concerned mainly with the development of perfusion tracers, the biodistribution of which reflect the regional blood flow to areas of major organs such as the heart and brain. However, a major new direction of interest now lies in the development of receptor-binding radio-tracers which can be used to perform in-vivo characterisation of diseased tissues and it is likely that much of the future research in this field will follow this direction. The difficulties in developing such tracers are considerable. The researcher must first identify a promising target for radiopharmaceutical development. High specific activity radioactive molecules must be designed and synthesised which will both bind to the target receptor with high affinity, and also have the physicochemical characteristics which will allow them to reach the target site in sufficient quantity while at the same time showing minimal uptake in non-target tissues. Thus the knowledge base required for radiophannaceutical development has now expanded beyond the limits of radiopharmaceutical chemistry to include aspects of biochemistry, molecular biology and conventional drug design. The portfolio of basic knowledge required to support current radiopharmaceutical development is changing and scientists working in this arena need to be trained in this regard. At the same time, the very latest developments in the field need to be communicated to the scientific community in order to stimulate the advancement of this exciting new direction of research.

A great deal of experimental, clinical and epidemiological data have been gathered to confirm the strict and causal correlation between plasma lipoproteins and coronary heart disease. However, as usually happens in research, many more interesting issues are being studied, opening new fields of research for the future. These new advances, together with the combined efforts of cell biologists and lipoprotein chemists, have set the pace for an exciting period of research and clinical applications of diets and drugs affecting plasma and cell lipids. This volume, which includes the work of many of the leading world labortories, represents an authoritative and up-to-date appraisal of the status of the art and a stimulus to future research at the laboratory and clinical level in a fascinating area of clinical and preventive medicine.

This volume is the proceedings of the William Harvey Research Conference held in Cannes, France, on the 20th and 21st March, 1997. It describes the present knowledge of the structures of the cyclooxygenase isoforms and the experimental and clinical effects of selective inhibitors of cyclooxygenase-2. The pathophysiological significance of the cyclooxygenase enzymes in tumorigenesis, programmed cell death, vascular disease and asthma is also covered.

This book continues as volume 6 of a multi-compendium on Edible Medicinal and Non-Medicinal Plants. It covers edible fruits/seeds used fresh, cooked or processed into other by-products, or as vegetables, cereals, spices, stimulant, edible oils and beverages. It covers selected species from the following families: Sapindaceae, Sapotaceae, Schisandraceae, Solanaceae, Thymelaeaceae, Urticaceae, Vitaceae and Winteraceae. This work will be of significant interest to scientists, researchers, medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, agriculturists, botanists, conservationists, lecturers, students and the general public. Topics covered include: taxonomy; common/English and vernacular names; origin and distribution; agroecology; edible plant parts and uses; botany; nutritive and pharmacological properties, medicinal uses and research findings; nonedible uses; and selected references.

This book is intended to serve as a resource for analysts in developing and troubleshooting sample preparation methods. These are critical activities in providing accurate and reliable data throughout the lifecycle of a drug product. This book is divided into four parts: * Part One covers dosage form and diluent properties that impact sample preparation of pharmaceutical dosage forms and the importance of sampling considerations in generating data representative of the drug product batch. * Part Two reviews specific sample preparation techniques typically used with pharmaceutical dosage forms. * Part Three discusses sample preparation method development for different types of dosage forms including addressing drug excipient interactions and post extraction considerations, as well as method validation and applying Quality by Design (QbD) principles to sample preparation methods. * Part Four examines additional topics in sample preparation including automation, investigating aberrant potency results, green chemistry considerations for sample preparation and the ideal case where no sample preparation is required for sample analysis.

A powerful collection of readily reproducible cutting-edge techniques for characterizing the ligand or substrate binding of neurotransmitter receptors and transporters. The procedures cover interdisciplinary interactions for monoamine transporters, amino acid transporters, ionotropic receptors, metabotropic glutamate receptors, GABA receptors, and other G protein-coupled receptors. By illuminating how neurons in the central nervous communicate with other, these techniques can lead to the development of novel therapeutic strategies for neurological diseases.

In this era of biotechnology there have been many books covering the fundamentals of recombinant DNA technology and protein chemistry. However, not many sources are available for the pharmaceutical develop ment scientist and other personnel responsible for the commercialization of the finished dosage forms of these new biopharmaceuticals and other products from biotechnology. This text will help to fill this gap. Once active biopharmaceutical molecules are candidates for clinical trial investigation and subsequent commercialization, a number of other activities must take place while research and development on these molecules continues. The active ingredient itself must be formulated into a finished dosage form that can be conveniently used by health care professionals and patients. Properties of the biopharmaceutical molecule must be clearly understood so that the appropriate finished product formulation can be developed. Finished product formulation development includes not only the chemical formulation, but also the packaging system, the manufacturing process, and appropriate control strategies to assure such good manufacturing practice attributes as safety, identity, strength, purity, and quality."

Expert researchers and physician/clinicians describe in detail the newest and most commonly used technologies today in this rapidly advancing field. The authors provide readily reproducible methods for assessing the functional consequences of a certain polymorphism, evaluate the variety of genotyping platforms currently available, and discuss the management of pharmacogenomic information. Highlights include techniques for making a snapshot of the allele-specific variation in human gene expression, genome wide analysis of allele-specific expression using oligo microarrays, in vivo assays with HaploChIP, SNP genotyping in DNA pools, and PharmGKB, the pharmacogenetics and pharmacogenomics knowledge base. The methodologies for genotyping include denaturing high-performance liquid chromarography, pyrosequencing, kinetic-fluorescence detection, mass spectrometry, and TaqMan assay for insertion/deletions.

U-50,488 and the K receptor. Part II: 1991-1998.- Quantitative structure-activity relationships of antihypertensive agents.- Combinatorial chemistry: Polymer supported synthesis of peptide and nonpeptide libraries.- From genome to drug - optimising the drug discovery process.- Phosphodiesterase 4 (PDE4) inhibitors in asthma and chronic obstructive pulmonary disease (COPD.- Index Vol. 53.- Index of titles, Vol. 1-53.- Author and paper index, Vol. 1-53.

'Bad Science' hilariously exposed the tricks that quacks and journalists use to distort science, becoming a 400,000 copy bestseller. Now Ben Goldacre puts the $600bn global pharmaceutical industry under the microscope. What he reveals is a fascinating, terrifying mess. Doctors and patients need good scientific evidence to make informed decisions. But instead, companies run bad trials on their own drugs, which distort and exaggerate the benefits by design. When these trials produce unflattering results, the data is simply buried. All of this is perfectly legal. In fact, even government regulators withhold vitally important data from the people who need it most. Doctors and patient groups have stood by too, and failed to protect us. Instead, they take money and favours, in a world so fractured that medics and nurses are now educated by the drugs industry. The result: patients are harmed in huge numbers. Ben Goldacre is Britain's finest writer on the science behind medicine, and 'Bad Pharma' is the book that finally prompted Parliament to ask why all trial results aren't made publicly available - this edition has been updated with the latest news from the select committee hearings. Let the witty and indefatigable Goldacre show you how medicine went wrong, and what you can do to mend it.

This book is written for researchers, undergraduate students and postgraduate students, physicians and traditional medicine practitioners who develop research in the field of neurosciences, phytochemistry and ethnopharmacology or can be useful for their practice. Topics discussed include the description of depression, its biochemical causes, the targets of antidepressant drugs, animal and cell models commonly used in the research of this pathology, medicinal plants and bioactive compounds with antidepressant activity used in traditional medicine, advances in nanotechnology for drug delivery to the brain and finally the future challenges for researchers studying this pathology.

Information flow as nerve impulses in neuronal circuits is regulated at synapses. The synapse is therefore a key element for information processing in the brain. Much attention has been given to fast synaptic transmission, which predominantly regulates impulse-to-impulse transmission. Slow synaptic transmission and modu lation, however, sometimes have been neglected in considering and attempting to understand brain function. Slow synaptic potentials and modulation occur with a considerable delay in response to the accumulation of synaptic and modulatory inputs. In these contexts, they are plastic in nature and play important roles in information processing in the brain. A symposium titled "Slow Synaptic Responses and Modulation" was held as the satellite symposium to the 75th Annual Meeting of the Physiological Society of Japan on March 30-31, 1998, in Kanazawa. The theme was selected not only for the reason mentioned above, but also because of the considerable involvement of many Japanese scholars in establishing the basic issues. Following the dawn of synaptic physiological research, as Sir John Eccles, Sir Bernard Katz, and Professor Stephen Kuffler carried out pioneer work, Professor Kyozou Koketsu and Professor Benjamin Libet, the students of Sir John Eccles, and their colleagues established the concept of slow synaptic responses and modulation by studying vertebrate sympathetic ganglia. Since then, the concept has been ex panded with detailed investigations of both peripheral and central synapses at the levels of single ion channels, intracellular Ca"+ dynamics, intracellular transduc tion mechanisms, and genes.

This volume serves as a valuable handbook for the development of nanomedicines made of polymer nanoparticles because it provides researchers, students, and entrepreneurs with all the material necessary to begin their own projects in this field. Readers will find protocols to prepare polymer nanoparticles using different methods, since these are based on the variety of experiences that experts encounter in the field. In addition, complex topics such as, the optimal characterization of polymer nanoparticles is discussed, as well as practical guidelines on how to formulate polymer nanoparticles into nanomedicines, and how to modify the properties of nanoparticles to give them the different functionalities required to become an efficient nanomedicine for different clinical applications. The book also discusses the translation of technology from research to practice, considering aspects related to industrialization of preparation and aspects of regulatory and clinical development.