Thin layer chromatography (TLC) is well suited for performing enantioseparations for research as well as larger-scale applications. A fast, inexpensive, and versatile separation technique, there are many practical considerations that contribute to its effectiveness. Thin Layer Chromatography in Chiral Separations and Analysis is the first book to focus solely on the theory, capabilities, and applications of TLC for direct and indirect enantioseparations. The first part of the book examines the fundamental principles of chirality and TLC. It describes the necessary materials, laboratory equipment, procedures, and strategies for the separation, quantification, isolation, and analysis of chiral compounds. The second part evaluates the real-world enantioseparations and densitometric analyses. Emphasizing pharmaceutical applications, the book discusses chiral separation mechanisms and methods for analyzing the chiral purity of diastereoisomers, amino acids, beta-blockers, and NSAIDS. Topics also include commercial stationary phases and chiral modifiers of mobile phases. Thin Layer Chromatography in Chiral Separations and Analysis presents a unified perspective of theory and experimental details underlying the collective developments in the field. The book offers scientists in a variety of disciplines and levels of expertise a complete guide to understanding the current and potential applications of chiral TLC.

Since the last major compendium dedicated to cyclic nucleotide phosphodiesterases (PDEs) was published over 15 years ago, an enormous amount of progress has occurred in the field. There is great need for a centralized source for key information in this burgeoning and therapeutically important area of medical research. Cyclic Nucleotide Phosphodiesterases in Health and Disease provides an integrated volume covering PDE biology from genes to organisms. It examines phosphodiesterases as pharmacological targets as well as the development of specific PDE inhibitors as therapeutic agents. With contributions from pioneers in the field, individual chapters describe one of the 11 known mammalian PDE families including the molecular characteristics, structure, function, and traits unique to each. Characteristics of PDEs from lower organisms are also the subject of other chapters since they provide key insights into PDE functions and are also pharmacological targets for treatment of a variety of diseases in humans and domestic animals. Chapters on the current biomedical and therapeutic research on PDEs include studies on gene-targeted knockout strategies and compartmentation in cyclic nucleotide signaling. By unraveling the unique cellular roles for different PDEs, scientists are beginning to open the door to the therapeutic use of PDE inhibitors for the treatment of a number of pathological conditions including asthma and inflammation, pulmonary hypertension, erectile dysfunction, and stroke. By collating current information into a coherent and coordinated perspective, Cyclic Nucleotide Phosphodiesterases in Health and Disease provides an invaluable reference for industry and clinical scientists and points toward future directions of research and therapeutic advancements in developing selective inhibitors for these various enzymes.

Since the discovery of actin by Straub in the 1950's and the pioneering work of Oosawa on actin self-assembly in helical laments in the 1960's, many books and conference proceedings have been published. As one of the most essential p- teins in life, essential for movement in organisms rangingfrom bacteria to higher eukaryotes, it is no surprise that actin has fascinated generations of scientists from many different elds. Actin can be considered as a "living treasure" of biology; the kinetics and thermodynamics of self-assembly, the dissipative nature of actin po- merization, the molecular interactions of monomeric and polymerized actin with regulators, the mechanical properties of actin gels, and more recently the force p- ducing motile and morphogenetic processes organized by the actin nanomachine in response to signaling, are all milestones in actin research. Discoveries that directly derive from and provide deeper insight into the fundamental properties of actin are constantly being made, making actin an ever appealing research molecule. At the same time, the explosion in new technologies and techniques in biological sciences has served to attract researchers from an expanding number of disciplines, to study actin. This book presents the latest developments of these new multiscale approaches of force and movement powered by self-assembly processes, with the hope to opening our perspectives on the many areas of actin-based motility research.

A comprehensive guide for physicians conducting clinical research, this second edition addresses a broader research perspective. It includes information on the implications of the ICH Guidelines, current FDA regulations, and an Internet address directory. Everything the clinical trial manager, planner, monitor, and investigator need to know about the design, establishment, monitoring, and close-out of a trial is in this book. The chapters address the elements of clinical research, professional interactions, FDA regulations and good clinical practices guidelines, investigational agent management, designing a study and protocol development, conducting the study, and more.

NMR spectroscopy has undergone a revolution in recent years with the advent of several new methods overcoming the problems of sensitivity and resolution. Recent developments in biotechnology have made it easier and economical to introduce 13C, 15N and 2H into proteins and nucleic acids. At the same time, there has been an explosion in the number of NMR experiments that utilize such isotope labeled samples. Thus, a combination of isotopic labeling and multidimensional, multinuclear NMR has opened up new avenues for structural studies of proteins, nucleic acids and their complexes.

This book will focus on recent developments in isotope labeling methods for structural studies of small molecules, peptides, proteins and nucleic acids. The aim of the book is to serve as a compendium of isotope labeling for the biomolecular NMR community providing comprehensive coverage of the existing methods and latest developments along with protocols and practical hints on the various experimental aspects. The book will cover a wide range of topics in isotope labeling under one title including emerging areas of metabolonomics and solid state NMR.

Emphasizing the role of good statistical practices (GSP) in drug research and formulation, this book outlines important statistics applications for each stage of pharmaceutical development to ensure the valid design, analysis, and assessment of drug products under investigation and establish the safety and efficacy of pharmaceutical compounds. Coverage include statistical techniques for assay validation and evaluation of drug performance characteristics, testing population/individual bioequivalence and in vitro bioequivalence according to the most recent FDA guidelines, basic considerations for the design and analysis of therapeutic equivalence and noninferiority trials.

It is estimated that 80 to 90% of drugs under development never make it to the marketplace due to insufficient clinical activity, unacceptable toxicity, rapid appearance of drug resistance, or other factors that should be, at least partially, predictable from preclinical testing. This new text asks the question, "How can we use computational methods to improve the success rate in drug development?" Computer Techniques in Preclinical and Clinical Drug Development shows how modeling makes it possible to extract the maximum amount of information and predictive value from preclinical data. Computer modeling methods from the areas of pharmacokinetics, pharmacodynamics, cytokinetics, and inhibition kinetics of multi-enzyme pathways are all discussed in this unique reference source.

This open access book is the first published guide about how to analyse data produced by the EQ-5D, one of the most widely used Patient Reported Outcomes questionnaires world wide. The authors provide practical, clear and comprehensive guidance in five concise chapters. Following an overview of the EQ-5D and its analysis, we describe how the questionnaire data - the EQ-5D profile and EQ VAS - can be analysed in different ways to generate important insights into peoples' health. We then show how the value sets which accompany the EQ-5D can be applied to summarise patients' data. The final chapter deals with advanced topics, including the use of Minimally Important Differences, case-mix adjustment, mapping, and more. This book is essential for those new to analyzing EQ-5D data and will be also be valuable for those with more experience. The methods can be applied to any EQ-5D instrument (for example, the three- and five-level and Youth versions) and many of the methods described will be equally relevant to other Patient Reported Outcomes instruments.

Neuroprotection in Autism, Schizophrenia and Alzheimer's Disease provides an up-to-date overview on recent clinical studies and the similarities discovered in the most prevalent brain disorders. The book's content will help shed light on basic mechanisms and provide new avenues for early diagnosis toward disease prevention and disease modification. It is written for researchers, clinicians and medical physicians in neuroscience, neurology and psychiatry. Sections discuss the shared pathophysiological mechanisms that underlie autism, schizophrenia/mood disorders and Alzheimer's disease, i.e. neurodevelopmental disorders, neuropsychiatric diseases and neurodegenerative disorders.

Taking readers from the research laboratory to the bedside, this Second Edition compiles essential information on the pharmacodynamics of all major classes of the antimicrobial armamentarium including penicillins, cephalosposorins, cephamycins, carbapenems, monobactams, aminoglycosides, quinolones, macrolides, antifungals, antivirals, and emerging agents currently in development. Written by experienced professionals in the field, this guide uses an abundance of examples to depict methods to apply pharmacodynamic concepts to everyday clinical practice.

This book reviews the history, regulatory status, pharmacopeial specifications, and harmonization of pharmaceutical excipients in the United States and Europe, and provides a comprehensive understanding of the current scientific basis for safety evaluation and risk assessment. Examines excipients as a unique class of products and explores new procedures for determining toxicity! A timely and unique addition to the pharmaceutical literature, containing over 570 citations that support and enhance the text, Excipient Toxicity and Safety identifies the differences between excipients (inactive ingredients), food ingredients, and drug products evaluates issues of dose administration, species selection, and study design for various routes of exposure provides detailed information on the historical uses of excipients in drug formulations clarifies the Safety Committee of the International Pharmaceutical Excipients Council's (IPEC) guidelines and technical specifications for conducting tests for each route of exposure explains how data generated in toxicity models are applied to identify hazards in drug formulations details exposure assessment to link hazard identification with risk considers the requirements and importance of purity specifications and much more! Excipient Toxicity and Safety is a blue-ribbon reference ideal for pharmacists; toxicologists; pharmacologists; analytical chemists; quality control, quality assurance, and regulatory compliance managers; and upper-level undergraduate and graduate students in these disciplines.

Volume 63 of "Progress in Drug Research" is devoted to recent developments in targeted cancer therapy. Significant advances in the fields of molecular and tumor biology over the past decade have led to this exciting new era in c- cer therapeutics with an intensive effort in rationally-designed cancer the- peutic strategies directed against selective molecular targets. These selective approaches may ultimately lead to tailoring treatments to individual patients where molecular biomarkers of sensitivity to therapy are identified, prod- ing better tolerated therapies with less side effects than past experiences with cytotoxic cancer chemotherapy, and reducing cancer to a controlled, chronic state. This volume contains eleven chapters, including updated reviews on a range of targets, such as tumor angiogenesis, apoptosis/cell survival pa- ways, and various inhibitors of cyclin-dependent kinases, cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and histone deacetylases (HDAC). Additional topics, including target validation, polypharmacology and potential synergy of involving multiple targets, antisense approaches, animal models for preclinical development of targeted agents, and obstacles, including development of resistance are also presented. In addition, the p- ticular challenges involved in translating preclinical data to clinical appli- tion are discussed. It gives me great pleasure to present this new volume. I would like to express my gratitude to the chapter authors, to Birkhauser Verlag and, in particular, to Dr. Beatrice Menz and Ms. Gabriele Poppen for their assistance in compiling and editing this volume. April 2005 Richard M. Schultz vii Progress in Drug Research, Vol. 63 (R. M. Schultz, Ed.

The overall aim of this work is to provide a reference book which describes the general framework for conducting GCP-compliant clinical research, particularly pharmaceutical industry clinical research. Wendy Bohaychuk and Graham Ball run a consultancy, GCRP Ltd., which has conducted over 820 GCP audits involving more than 200 companies in the last 10 years. More than 5,000 individuals have been involved in their training courses to help people perform GCP-compliant clinical research. They have authored several books and articles including:

• Standard operating procedures for investigators
• Standard operating procedures for sponsors and CROs
• GCP — an indexed reference

Drawing on their wealth of experience, they have produced this enlightening and practical reference work which fills an educational gap in the understanding of GCP at all levels. Written in concise language simple enough to be accessible to those new in the field, the dozens of real-life stories and detailed case studies at the end of each chapter make the book an invaluable resource for the more experienced, highlighting what can go wrong in a clinical study: A study of prostate cancer in the UK - An investigator brochure was not provided. The company argued that a brochure was unnecessary because the drug was already marketed. Indeed it was — for hypertension! A study of cardiovascular surgery in the UK - The consent dates were changed (by overwriting) to indicate that the patients had provided consent before the study started. The original dates post-dated the start of the study. A study of hypertension in Germany - The investigator brochure predated the study by nine years! Checklists are provided throughout the book to help monitors, auditors and investigators ensure that nothing important is overlooked. The authors present the topic of GCP with remarkable clarity, insight and enthusiasm emphasizing that this code of practice was not designed to make studies more difficult for investigators or more expensive for sponsors and CROs but, in the final analysis, to ensure the safety and well-being of study participants and future patients who will benefit from well-conducted, GCP-compliant studies.

Sponsor companies and CROs alike will appreciate the industry-wide analysis, practical, how-to advice, and helpful charts and checklists provided by Outsourcing in Clinical Drug Development. A panel of experts discuss supplier identification and selection, financial considerations, and the ethical issues. They cover contracting out laboratory analysis, data management, and statistical services, and the effects of outsourcing on quality assurance. Whether readers are beginning to explore the possibility of outsourcing or already involved in long-term strategic outsourcing partnerships, this invaluable resource is a complete guide to the drug development outsourcing relationship.

Increase in antibiotic resistance has forced researchers to develop new drugs against microorganisms. Lipopeptides are produced as secondary metabolites by some microorganisms. Computer-aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates provides the identification of novel ligands for different antimicrobial lipopeptides. Along with identification, it also provides some of the in silico drug design processes, namely homology modelling, molecular docking, QSAR studies, drug ADMET studies and pharmacophore studies to check the ligand-lipopeptide interaction. Some lipopeptides have shown anti-cancerous properties too, and this book discusses the required templates to design new drugs using computational techniques. Key Features: Focuses on the use lipopeptides as new antimicrobial compounds Presents the basics of in silico modelling for design and development of new drug molecules, and is therefore of interest to beginners in the field Provides a step-by-step process for identification of drug molecules and testing its efficacy in silico Couples with courses on patents and intellectual property rights

Legal in 23 states as of June 2014, medicinal Cannabis sativa is widely used, with mainstream news and scientific sources reporting success stories of people suffering from such diverse medical conditions as epilepsy, cancer and chronic pain. In states where it remains illegal, however, providers of medicinal cannabis risk arrest. While the United States government restricts medicinal cannabis research, advances have been made in Israel, Spain and Italy. One such breakthrough was the discovery of cannabinoids (compounds found in cannabis) that mimic endogenous neurotransmitters in the brain and in the immune system, and are thus likely to be able to directly affect a host of degenerative diseases. Focusing on the biochemical properties, medical benefits and psychological effects of cannabinoids, this book provides an overview of current research and clinical trials, examines the rationales behind cannabis' status as a Schedule I narcotic and discusses the uses of industrial hemp.

Once the existence of free radicals was proven, an avalanche of studies on free radical-mediated biological processes ensued. The study of reactive oxygen and nitrogen species (ROS and RNS) is center stage in biological free radical investigations. Written by a biochemist, Signaling Mechanisms of Oxygen and Nitrogen Free Radicals discusses the regulatory functions of ROS and RNS in physiological and pathophysiological states. An exploration of the main questions of signaling mechanisms of reactive oxygen and nitrogen species in enzymatic processes, this book draws attention to the chemical mechanisms of these reactions. It elucidates the differences between signaling functions and damaging effects of ROS and RNS in biological systems. The text also covers free radical signaling processes catalyzed by enzymes, producers of superoxide and nitric oxide that are able to use produced ROS and RNS as signaling species in their own catalytic processes. It then examines ROS and RNS signaling produced by mitochondrial enzymes. The author explores signaling functions of ROS and RNS in enzymatic heterolytic reactions, supplying important data on ROS and RNS signaling in the catalysis by the enzymes which do not produce free radicals by themselves. He provides information on signaling by reactive oxygen and nitrogen species in apoptosis and aging/senescence and concludes with coverage of mechanisms of free radical signaling in enzymatic processes. The book provides new understanding of signaling functions in living organisms related to cardiovascular processes, cancer, inflammation, hereditary diseases, and their regulation of physiological functions such as development, aging, and senescence. This information can support the development of new drugs and novel treatment methods.

Lectins have in the past been regarded by many scientists as curious proteins of uncertain structure and specificity that bind to carbohydrates of dubious significance themselves. All this is rapidly changing. The functional importance of glycosylation in cell-cell and cell-pathogen interactions, as well as intracellular events, has been recognized by the explosion of the science of glycobiology. This has been paralleled by the realization that lectins, once they have been well characterized, can be extremely useful tools for exam- ing structural changes in glycosylation and their functional consequences for human pathophysiology. Different lectins vary considerably in their degree of specificity. Some, such as wheatgerm agglutinin, have fairly broad specificity (for glucosamine or sialic acid), whereas others, such as Maackia amurensis, are specific not only for a single carbohydrate, but also for its linkage (2-3 linked sialic acid). Lectins with relatively broad specificity may be very useful as an adjunct to isolation or quantification of soluble glycoproteins, whereas lectins of known, and precise, specificity will be more useful for characterization of carbo- drate structure. We have included an appendix in Lectin Methods and Pro- cols that provides the known specificities of all lectins cited in the text.

Presents the latest developments on the interaction of metal complexes with nucleic acids, the building blocks of life. Bioinorganic chemistry is a highly interdisciplinary area of research and is of great interest to scientists working in the fields of coordination chemistry, biochemistry, supramolecular chemistry, nanotechnology, computational chemistry, and inorganic chemistry in general. Includes the latest research in DNA recognition by supramolecular metal complexes. Describes the applications of this exciting area of research in metal-nucleic acid chemistry.

This book features multi-omics big-data integration and data-mining techniques. In the omics age, paramount of multi-omics data from various sources is the new challenge we are facing, but it also provides clues for several biomedical or clinical applications. This book focuses on data integration and data mining methods for multi-omics research, which explains in detail and with supportive examples the “What�, “Why� and “How� of the topic. The contents are organized into eight chapters, out of which one is for the introduction, followed by four chapters dedicated for omics integration techniques focusing on several omics data resources and data-mining methods, and three chapters dedicated for applications of multi-omics analyses with application being demonstrated by several data mining methods. This book is an attempt to bridge the gap between the biomedical multi-omics big data and the data-mining techniques for the best practice of contemporary bioinformatics and the in-depth insights for the biomedical questions. It would be of interests for the researchers and practitioners who want to conduct the multi-omics studies in cancer, inflammation disease, and microbiome researches.

Contains papers from the October 1995 symposium, in sections on general aspects, transgenics, and immunology and infectious diseases. Topics include ultrastructure of the liver in piglets fed dietary oils, artificial surfactant as a vehicle for endotracheal epinephrine in pediatric porcine cardiopul

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes."

The purpose of this book is to provide information which supports the fact that rat hybridomas are no more difficult to develop than mouse hybridomas. This is the first book devoted to the development of rat hybridomas. It includes theories, step-by-step techniques, ingredients and apparatus. The focus of this work is on the antibody repertoire, the unique biological properties of rat immunoglobulins, the one-step purification procedure by immunoaffinity chromatography, the absence of C-type particles, and the easy production of large amounts of ascitic fluid containing rat MAb. This rare publication is an absolute must for all scientists using MAbs and those interested in the fields of immunology, biotechnology, and biochemistry.

Gives a convenient summary of trials in Gynecologic Oncology Supplies an invaluable revision primer for those undertaking certification Provides a uniquely up-to-date resource

The volume aim to be a comprehensive overview of the drug and biologic development process that is often called "the valley of death" (pre-IND through approval) where high costs of studies and high rates of product failure are part of the drug development landscape. Imaging tools can serve in this period by adding high value data, the images and the kinetic information they can provide, and cost-effective development alternative tools which potentially improve pivotal study designs. Imaging may identify safety issues early such as unwanted organ or tissue distributions, and then can serve advanced development with added certainty of a drug or biologic's success to senior corporate management and investors. There are numerous textbooks, reference texts and treatises on medical imaging technologies, teaching tools on medical cases and physics books on the science of detector and computer interface systems. Rarely, in each of these are examples of medical imaging protocols and animal models of disease i.e. a text on methodology in drug development is currently unavailable.