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Experimental science is a complicated creature. At the head there is a Gordian knot of ideas and hypotheses; behind is the accumulated mass of decades of research. Only the laboratory methods, the legs which propel science forward, remain firmly in touch with the ground. Growth, however is uneven; dinosaurs develop by solid means to give a vast body of results, but few ideas. Others sprint briefly to success with brilliant, though ill-supported, ideas. The problems which this book addresses is to maintain an organic unity between new ideas and the current profusion of innovative experimental tools. Only then can we have the framework on which our research thoughts may flourish. The contributors are outstanding scientists in their respective fields and they record here in a clear manner the methodology with which they perform their experiments. They also illustrate some of their most exciting findings. In all chapters the emphasis is on the critical analysis of the methodology which is often avoided in refereed Journals. These techniques are explained in this book in adequate detail. Each chapter is extensively referenced and contains the most recent material available from author's laboratory at the time of going to press.

nd The 22 meeting of the International Society on Oxygen Transport to Tissue (LS. O. T. T.) of which this volume is the scientific proceedings, was held in Istanbul, Turkey on August 22-26, 1994. It was a historical occasion in that it was almost 200 years to the day that one of the founding fathers of oxygen research, Antoine Lavoisier, on May 8, 1794 found his early demise at the hands of the guillotine. This spirit of history set the tone of the conference and in the opening lecture the contribution that this part of the world has given to the understanding of oxygen transport to tissue was highlighted. In particular, the contribution of Galen of Pergamon (129-200) was discussed who for the first time demon­ strated that blood flowed through the arteries and whose view on the physiology of the circulation dominated the ancient world for well over a millennium. A forgotten chapter in the history of the circulation of the blood is the contribution made by Ibn al Nafis of Damascus (1210-1280) who for the first time described the importance of the pulmonary circulation by stating that all venous blood entering the right ventricle ofthe heart passes to the left ventricle, not through pores in the septum of the heart as had been postulated by Galen, but through the circulation of the lungs.

DRUG TRANSPORTERS Drug transporter fundamentals and relevant principles and techniques, featuring new and expanded chapters Drug Transporters: Molecular Characterization and Role in Drug Disposition provides in-depth analysis of the conceptual evolution and technical development for studying drug transporters. Contributions by an international panel of leading researchers address advances in transporters as drug targets, transporters in pharmacotherapy, the impact of transporters on drug efficacy and safety, the development of sophisticated model systems and sensitive assay methods, and more. Divided into two parts, the book first provides a thorough overview of relevant drug transporters before detailing the principles of drug transport and associated techniques. The updated and expanded third edition includes new chapters on in vitro-in vivo scale-up of drug transport activities, the ontogeny of drug transporters, the application of physiologically-based pharmacokinetic and pharmacodynamic modeling, and the use of transporters as therapeutic targets for diseases. Reflects the current state of the field and offers perspectives on future directions Covers basic knowledge, clinical outcomes, and emerging discoveries in transporter science Provides up-to-date information on drug transporter families, mechanisms, and clinical implications Includes extensive references and numerous figures and tables throughout Understandable for novices while offering sufficient depth for more experienced researchers, Drug Transporters: Molecular Characterization and Role in Drug Disposition, Third Edition is an excellent textbook for pharmacological or physiological science courses in drug/membrane transport, and an invaluable reference for academic or industrial scientists working in the transporter field and related areas of drug metabolism, pharmacokinetics, and pharmacodynamics.

This new edition overviews drug transporters and presents the principles of drug transport and associated techniques, featuring new chapters on multidrug and toxin extrusion proteins, placental transport, in silico approaches in drug discovery, and regulatory guidance for drug transport studies in drug development. • Describes drug transporter families, mechanisms, and clinical implications along with experimental methods for studying and characterizing drug transporters • Includes new chapters on multidrug and toxin extrusion proteins, placental transport and in silico approaches in drug discovery • Has a new chapter covering regulatory guidance for the evaluation of drug transport in drug development with global criteria used for drug transporters in clinical trials • Arranges material to go from fundamental mechanisms to clinical outcomes, making the book useful for novice and expert readers

This volume contains refereed manuscripts prepared from presentations made at the 2ih annual meeting of the International Society on Oxygen Transport to Tissue (ISOTT). The meeting was held in Hanover, NH, USA, at Dartmouth Medical School, the 3rd oldest medical school in the USA. ISOTT attempts to produce high quality pUblications on cutting edge topics relating to oxygen in living systerns. The goal is to allow contributors to contribute original data, as with a main-stream journal article, but also to voice individual opinions and ideas in a more relaxed scientific forum. The meeting brought together an international group of scientists who share a common interest in the measurement and role of oxygen in living systems. The organizers of ISOTT99 made a special effort to bring together people from industry, medicine, and basic sciences in order to improve the links in the chain of discovery through to application. As a result, this volume contains publications on a range of subjects. There are contributions from companies on modifiers of oxygen carrying capacity (allosteric modifiers of hemoglobin and infusible oxygen carriers or blood substitutes); technical reports on oxygen measurement devices including advances in near-infrared spectroscopy and imaging, oxygen electrodes, magnetic resonance spectroscopy and imaging, and fluorescence based measurements. There are medically related sections on modifying and measuring tumor oxygenation in order to improve therapy, assessment and interpretation of oxygenation in the central nervous system, and general issues relating oxygen to pathological conditions.