Germination of the thought of "Enzymatic- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges" Proceedings came about as part of the annual meeting of The American Association of Pharmaceutical Scientists (AAPS) that was held in San Diego in November of 2007. The attendance of workshop by more than 250 pharmaceutical scientists reflected the increased interest in the area of drug-drug interactions (DDIs), the greater focus of PhRMA, academia, and regulatory agencies, and the rapid pace of growth in knowledge. One of the aims of the workshop was to address the progress made in quantitatively predicting enzyme- and transporter-based DDIs as well as highlighted areas where such predictions are poor or areas that remain challenging for the future. Because of the serious clinical implications, initiatives have arisen from the FDA (http://www.fda.gov/cber/gdlns/interactstud.htm) to highlight the importance of enzyme- and transporter-based DDIs. During the past ten to fifteen years, we have come to realize that transporters, in addition to enzymes, play a vital role in drug elimination. Such insight has been possible because of the continued growth in PK-ADME (pharmacokinetics-absorption-distribution-metabolism-excretion) knowledge, fueled by further advances in molecular biology, greater availability of human tissues, and the development of additional and sophisticated model systems and sensitive assay methods for studying drug metabolism and transport in vitro and in vivo. This has sparked an in-depth probing into mechanisms surrounding DDIs, resulting from ligand-induced changes in nuclear receptors, as well as alterations in transporter and enzyme expression and function. Despite such advances, the in vitro and in vivo study of drug interactions and the integration of various data sets remain challenging. Therefore, it has become apparent that a proceeding that serves to encapsulate current strategies, approaches, methods and applications is necessary. As Editors, we have assembled a number of opinion leaders and asked them to contribute chapters surrounding these issues. Many of these are the original Workshop speakers whereas others had been selected specially to contribute on topics related to basic and applied information that had not been covered in other reference texts on DDI. The resulting tome, entitled Enzyme- and Transporter-Based Drug Interactions: Progress and Future Challenges, comprises of four sections. Twenty-eight chapters covering various topics and perspectives related to the subject of metabolic and transporter-based drug-drug interactions are presented.

The medical profession requires extensive training and preparation in order to ensure the success and competency of future doctors and healthcare professionals. With an emphasis on professional development and medical education, current professionals in this field acknowledge the importance of residency programs and training in the professional development of future doctors. Optimizing Medicine Residency Training Programs presents a comprehensive overview of chapters ranging from the history of medicine to opportunities and research for further exploration geared toward the professional development and medical training for the next generation of doctors and healthcare professionals. This publication is an essential reference source for academicians, practitioners, and professionals interested in the education and training of modern medical professionals.

Leading practitioners detail revolutionary new spectrometric techniques for the identification and covalent structural characterization of macromolecules, proteins, glycoconjugates, and nucleic acids. Based on the Fourth International Symposium on Mass Spectrometry in the Health and Life Sciences held in San Francisco in 1998, this invaluable book contains tested strategies for solving many significant biomedical research problems. The techniques use mass spectrometry, automated computer processing of spectral information, and gene, protein, and EST databases for genomic and proteomic correlations. Mass Spectrometry in Biology and Medicine offers a unique opportunity to explore and apply these new techniques of mass spectrometry that are revolutionizing the identification and structural characterization of proteins, carbohydrates, and nucleic acids.

The increased attendance required concurrent sessions for the 48 oral presentations and 190 submitted posters (for more details see Website: www.ct.ornl.gov/symposium). Attendees came from Australia, Austria, Belgium, Brazil, Canada, China, Denmark, Finland, Germany, Hungary, India, Japan, Korea, Mexico, The Netherlands, Russia, South Korea, Spain, Sweden, Turkey, and Ven ezuela, as well as from the United States. This international perspective was continued in a Special Topic Ses sion sponsored by the International Energy Agency (lEA) Bioenergy Pro gram on Biofuels and chaired by Jack Saddler and David Gregg from the University of British Columbia. Several of the 10 member countries in this network are approaching Demonstrations of the Biomass-to-Ethanol pro cess and have a range of more fundamental projects that look at various aspects of pretreatment, enzymatic hydrolysis, fermentation, and lignin utilization. Presenters from several of the participating countries described their country's biomass-to-ethanol projects, and differential factors such as the type of biomass available, the maturity of the wood or agricultural processing industry, and the willingness of government to bear the risk/ cost of development and demonstration."

Fatty acids play an important role in the barrier function of skin and represent a major source of proinflammatory mediators such as prostaglandins, leukotrienes and other lipids in inflammatory skin disorders. This book combines the two major functions of fatty acids in skin biology. In the first part the biosynthesis of fatty acids in skin with its role in barrier function as well as the role of dietary fatty acids on skin cell function and in the treatment of inflammatory skin diseases is presented. The second part deals with skin as a source of proinflammatory eicosanoids, especially with the keratinocyte as a major cellular source. Metabolism of eicosanoids in skin, its role in psoriasis and atopic dermatitis as well as pharmacological inhibition of eicosanoid biosynthesis is reviewed. The book finishes with a chapter describing the methods used for quantification of fatty acids and derivatives in skin inflammation. Anyone interested in skin physiology would benefit from the overviews about the two sites of fatty acids' function in skin integrity and in skin inflammation.

The polymerase chain reaction (PCR) is one of the most important molecular biological methods ever devised, with numerous applications to cli- cal molecular medicine. Since its description in 1985, PCR has undergone tremendous improvements, and many variations on the basic PCR theme have been published. With such a large volume of PCR-related literature, a clinical scientist wishing to use the technique will have a difficult task loc- ing the relevant information to implement it effectively. There is thus clearly a need for an up-to-date volume with detailed protocols to facilitate the setting up of those techniques most relevant to clinical applications. Unlike some other books on this topic, Clinical Applications of PCR includes only methods that are of direct relevance in clinical settings. The book is organized in three parts: an introductory section, a section on general methodology, and a final section with specific clinical applications. The first section covers the basic principles of PCR and is most useful to those new to molecular diagnosis. The next chapter includes useful tips for setting up a PCR laboratory. Section 2 then outlines some of the most commonly used PCR-based techniques in molecular diagnosis. Section 3 includes carefully chosen examples that represent typical applications of PCR in diverse clinical fields, encompassing hematology, oncology, genetics, and microbiology.

Superantigen Protocols assembles experimental protocols that have proved useful for the study of superantigens. These techniques will allow researchers from various areas of cell biology, microbiology, immunology, biochemistry, and molecular biology to assess the physical characteristics and biological effects of well-known superantigens as well as of putative substances that might have superantigenic activities, and to explore therapies for superantig- induced effects. Microbial exotoxins have been studied for decades as virulence factors because of their pathogenic effects. The term "superantigen" was coined by Marrack and Kappler a decade ago for some of these molecules because of their potent T-cell stimulatory activities. In recent years, advances in mole- lar biology provide recombinant as well as natural superantigens in highly purified form for physical characterization. Superantigens are now used extensively as tools to study interactions between receptors on cells of the immune system as they bind to major histocompatibility complex class II m- ecules on antigen-presenting cells and V regions of T-cell receptors. The b- ? logical effects that result from these interactions are studied both in vitro and in vivo. The intent of this book is, therefore, to bring together up-to-date te- niques developed by experts in the field of biochemistry, immunology, and molecular biology for the study of superantigens. Superantigen Protocols begins with an overview of the field to provide background information on the various classes of superantigens and their str- ture.

The present volume is the first in the advances in oncobiology series. It is meant to be useful not only to clinical and non-clinical oncologists but also to graduate students and medical students. The individual chapters are presented as self-contained summaries of current knowledge rather than as reviews. The last chapter deals with the subject of chemotherapy.

This 8-volume set provides a systematic description on 8,350 active marine natural products from 3,025 various kinds of marine organisms. The diversity of structures, biological resources and pharmacological activities are discussed in detail. Molecular structural classification system with 264 structural types are developed as well. The 3rd volume mainly illustrates the molecular formula and structures of alkaloids. .

A readily reproducible collection of established and emerging techniques for studying the interaction between proteins and ligands, including biochemical/bulk techniques, structure analysis, spectroscopy, single-molecule studies, and theoretical/computational tools. Among the highlights are surface plasmon resonance (SPR) and reflectometric biosensor approaches, high-throughput screening with confocal optics microscopy, single molecule fluorescence and fluorescence correlation spectroscopy (FCS), atomic force microscopy (AFM), crystallography of reaction intermediates, and time-resolved x-ray crystallography. The protocols follow the successful Methods in Molecular Biologya"[ series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

The tools of molecular biology have revolutionised our understanding of gene structure and function and changed the teaching of genetics in a fundamental way. The transition from classical genetics to molecular genetics was initiated by two discoveries. One was the discovery that DNA has a complementary double helix structure and the other that a universal genetic code does exist. Both led to the acceptance of the central dogma that RNA molecules are made on DNA templates.
The last twenty years have seen remarkable growth in our knowledge of molecular genetics, most of which is the outcome of recombinant DNA technology. This technology which is not limited to cloning, sequencing, and expression has created a biotechnology industry of its own, the purpose of which is to develop new diagnostic and therapeutic approaches in medicine. Both industries in collaboration with the biomedical community are now engaged in laying down the foundation of molecular medicine.
The present volume seeks to provide a coherent account of the new science of molecular genetics. Its content however is by no means exhaustive, partly because of the publication explosion but more because of space restrictions. A rudimentary knowledge of genetics on the reader's part is assumed. Quite understandably, considerable emphasis is placed on major technical advances but not without expounding numerous new ideas and phenomena including alternative splicing, POR, DNA methylation, genomic imprinting, and so on.

This 8-volume set provides a systematic description on 8,350 active marine natural products from 3,025 various kinds of marine organisms. The diversity of structures, biological resources and pharmacological activities are discussed in detail. Molecular structural classification system with 264 structural types are developed in the book as well. The 2nd volume continuously illustrates the molecular formula and structures of terpenoids.

The first section of this volume consists of five chapters to the nature of membrane transport systems. A chapter on secondary active glucose transport has been omitted because this topic is slated to appear in the Nephrobiology module. Chapter 6 deals with oxidase control of plasma membrane proton transport, while chapter 7 addresses the question of how cell volume is regulated. Although we chose not to have a separate chapter covering additional co-transport systems namely, Na+ -K+ -2CI-, KCI, -HCO-3, as well as CI- -HCO-3 exchange and K+ and CI- movements through channels, the role of each in cell volume regulation is emphasized in Chapter 7.
Instead of devoting an entire section to the thermodynamics of metabolism, we thought it desirable to have the subjects of medical imaging and NMR of cell metabolism discussed in some detail in two chapters. These are followed by a chapter on the thermodynamic instrument - the calorimeter. Calrimetry allows the measurement of net changes of heat in cells, tissues, organs and whole body. As will be recognized, heat dissipation does not arise only from chemical reactions but also from interactions between macromolecules and conformational changes in protein complexes and mass Ca2+ movement such as that occurring in contracting skeletal muscle. The last chapter provides an account of equilibrium and non-equilibrium thermodynamics and the enthalpy balance method. It reveals that calometric measurements are useful in studies of clinical and toxicological problems.

Many new antileukotriene drugs are now marketed as antiasthma drugs and represent the first new drugs in this field since the 1970s. This book covers the steps that have led to the discovery and development of these new drugs and offers detailed descriptions of their clinical applications. The review chapters on the main aspects of basic and applied leukotriene research are written by leading specialists in the field, and the volume takes a new approach in presenting information of particular interest to both scientists and clinicians in the fields of asthma, inflammation and allergic diseases.

An integrated survey of best practices for the management of patients with implanted prosthetic devices and an insightful examination of the epidemiological, societal, and policy issues associated with their use. The devices covered range from breast, penile, vascular, and joint prostheses to cochlear, ossicular, and dental implants, and include cerebrospinal fluid shunts, cardiac valves, stents, and pacemakers. For each device, the authors consider its pros and cons, detail the best current strategies to keep implanted patients healthy, and evaluate the latest and most promising new diagnostic tests, Clinical counterpoints from distinguished authorities at major centers in the United States and Europe are offered throughout. Follow-up recommendations are summarized in a standardized format that allows comparative analysis and lays the foundation for controlled clinical trials and the eventual establishment of evidence-based guidelines.

We are currently experiencing a fundamental shift in the way in which we approach the characterization of cancer. Never before has the make up of cancer tissues and individual cells been so exhaustively researched and char- terized. We are now capable of producing molecular "fingerprints" that ch- acterize the expression of all known and unknown genes within tumors and their surrounding tissues. More than 30,000 different genes may be measured in each patient's tumor in a single experiment. Simultaneously, novel therapies that exploit the molecular roadmap have been developed and are now being offered to patients. These novel agents, such as Glivec, Herceptin, Iressa, and others, specifically target individual genes within tumors and can produce d- matic responses in some patients. These drugs are only the forerunners of a coming tidal wave of novel therapeutics that individually target specific m- ecules within cancer cells-more than 300 such agents are currently in phase I or II clinical trials. This is an exciting time for cancer specialists and patients alike. However, if we have learned anything from the past 50 or more years of research into cancer, it is that Lord Beaverbrook, in founding the British national health service in the 1950s, was frighteningly prescient when he defined the primary goal of health care to be "Diagnosis, Diagnosis, Diag- sis. " Now, more than ever, it is essential that appropriate diagnostic methods and approaches are applied to the selection of patients for treatment.

The idea of editing this book was born in the winter of 1988/1989. Christian Endler was organizing the workshop 'Wasser und Information' (water and information) in Austria [1], and Jurgen Schulte was working on a publication of his results on atomic cluster stabilities and long-range electromagnetic interaction in atomic clusters. It was Franz Moser from the Technical University of Graz who brought these two together. After a talk that Moser had given in Bremen, Schulte explained to hirn his ideas about clusters and long range interaction, and his concern about reliable theories and experiments in research on ultra high dilutions (UHD) and homoeopathy. He was suggested to be a speaker at the Austrian workshop. Reviewing the contributions of this workshop and the current literature on UHD and homoeopathy, especially the PhD thesis by Giesela King [2] and the excellent survey by Marco Righetti [3], we decided to work on a book in order to critically encou rage more scientists to work and publish in this field with a high scientific standard. What we had in mind was a useful contribution to the goal to lift research on UHD and homoeo pathy to an internationally acceptable scientific standard, to encourage international scien tists to work in this area and to establish UHD and homoeopathy in academic science. Delayed by our individual academic careers in our specific fields, and delayed by lack of funds it took us about four years to finish this book.

This book, with its 16 chapters, documents the present state of knowledge of the adenosine A receptor. It covers a wide range of information, including data from 3 studies of theoretical, molecular and cellular pharmacology, signal transduction, integrative physiology, new drug discoveries and clinical applications. It fills an important gap in the literature since no alternative source of such information is currently available. Although the A receptor is increasingly being recognized for 3 its increasing number of biological roles throughout the body and many A receptor 3 ligands have proven useful in elucidating peripheral and central pathologies, many issues remain unresolved. Moreover, research activity in this field continues to grow exponentially, resulting in a constant flow of new information. The chapters in this book cover both basic science and the relevant applications and provide an authoritative account of the current status of the field. They have enabled my goal as editor to make "A Adenosine Receptors from Cell Biology to Pharmacology and 3 Therapeutics" an up to date, scientifically excellent, reference source, attractive to basic and clinical scientists alike, a reality. Detailed understanding of the physico-chemical aspects and molecular biology of the A receptor provides a solid basis for its future development as a target for 3 adenosine-based pharmacotherapies (Chapters 2 and 3).

In Human Cloning a panel of distinguished philosophers, medical ethicists, religious thinkers, and social critics tackle the thorny problems raised by the now real possibility of human cloning. In their wide ranging reviews, the distinguished contributors critically examine the major arguments for and against human cloning, probe the implications of such a procedure for society, and critically evaluate the "Report and Recommendations of the National Bioethics Advisory Commission." The debate includes both religious and secular arguments, as well as an outline of the history of the cloning debate and a discussion of human cloning's impact on our sense of self and our beliefs about the meaning of life.

A collection of cutting-edge techniques for studying ubiquitin-dependent protein degradation via the proteasome. The topics covered range broadly from basic biochemistry to cellular assays to discovery techniques using mass spectrometric analysis. These biochemical and cellular methods are necessary to explore the ubiquitin-proteasome system and ubiquitin-proteasome-dependent functions. State-of-the-art and user-friendly, Ubiquitin-Proteasome Protocols offers novice and experienced bench scientists alike a thorough compendium of readily reproducible techniques that will accelerate discovery, enhance productivity, and permit manipulation of the system for varied research purposes.

This two volume set introduces the up-to-date high-tech applications of Aggregation-Induced Emission (AIE) luminogens mainly in the areas of biosensing, bioimaging, and biomedicine. The 1st volume covers the applications of AIE materials in biosensing and bioimaging, including the technological utilizations in ionic/biomolecular sensing, bacterial imaging, cell imaging, intracellular microenvironment analysis, advanced optical imaging and multimodality, etc. It is an essential reference for materials scientists, chemists, physicists and biological chemists.

Cell Cycle Control and Dysregulation Protocols focuses on emerging methodologies for studying the cell cycle, kinases, and kinase inhibitors. It addresses the issue of gene expression in vivo and in vitro, the analysis of cyclin-dependent kinase inhibitors, protein degradation mediated by the proteosome, the analysis of the transformed cell phenotype, and innovative techniques to detect apoptosis. Because there are already many manuals and protocols available, along with commercial kits and reagents, a variety of the more common techniques have not been included in our book. The protocols described, based on rather sophisticated techniques for in vivo and in vitro studies, consist of molecular biology, biochemistry, and various types of immunoassays. Indeed, the authors have successfully accomplished an arduous task by presenting several topics in the simplest possible manner. We are confident that Cell Cycle Control and Dysregulation Protocols will facilitate and optimize the work of practical scientists involved in researching the cell cycle. We greatly acknowledge the extraordinary contribution of the authors in writing this book.

During the last decade, an increased interest in somatic stem cells has led to a flurry of research on one of the most accessible tissues of the body: skin. Much effort has focused on such topics as understanding the heterogeneity of stem cell pools within the epidermis and dermis, and their comparative utility in regenerative medicine applications. In Skin Stem Cells: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study skin stem cells. These include methods and techniques for the isolation, maintenance and characterization of stem cell populations from skin. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Skin Stem Cells: Methods and Protocols seeks to aid scientists in the further understanding of these diverse cell types and the translation of their biological potential to the in vivo setting.