The pace of new research and level of innovation repeatedly introduced into the field of drug delivery to the lung is surprising given its state of maturity since the introduction of the pressurized metered dose inhaler over a half a century ago. It is clear that our understanding of pulmonary drug delivery has now evolved to the point that inhalation aerosols can be controlled both spatially and temporally to optimize their biological effects. These abilities include controlling lung deposition, by adopting formulation strategies or device technologies, and controlling drug uptake and release through sophisticated particle technologies. The large number of contributions to the scientific literature and variety of excellent texts published in recent years is evidence for the continued interest in pulmonary drug delivery research. This reference text endeavors to bring together the fundamental theory and practice of controlled drug delivery to the airways that is unavailable elsewhere. Collating and synthesizing the material in this rapidly evolving field presented a challenge and ultimately a sense of achievement that is hopefully reflected in the content of the volume.

In the literature, several terms are used synonymously to name the topic of this book: chem-, chemi-, or chemo-informatics. A widely recognized de- nition of this discipline is the one by Frank Brown from 1998 (1) who defined chemoinformatics as the combination of "all the information resources that a scientist needs to optimize the properties of a ligand to become a drug. " In Brown's definition, two aspects play a fundamentally important role: de- sion support by computational means and drug discovery, which distinguishes it from the term "chemical informatics" that was introduced at least ten years earlier and described as the application of information technology to ch- istry (not with a specific focus on drug discovery). In addition, there is of course "chemometrics," which is generally understood as the application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors (2). The pharmaceutical focus of many developments and efforts in this area-and the current popularity of gene-to-drug or si- lar paradigms-is further reflected by the recent introduction of such terms as "discovery informatics" (3), which takes into account that gaining kno- edge from chemical data alone is not sufficient to be ultimately successful in drug discovery. Such insights are well in accord with other views that the boundaries between bio- and chemoinformatics are fluid and that these d- ciplines should be closely combined or merged to significantly impact b- technology or pharmaceutical research (4).

Psychopharmacology may be defined as the study of the effects of drugs on behavior. As an established scientific discipline, this is a relatively new area of research. Despite its short history, however, psychopharmacology has achieved a considerable degree of sophistication in the variety of experi mental approaches that are currently employed. Consequently, the interpretation of data accumulated through the use of various experimental laboratory techniques has become increasingly difficult and complex. Numerous excelIent texts and review articles are available that serve to outline recent progress in psychopharmacology (particularly the Handbook of Psychopharmacology series, edited by L. L. Iversen, S. D. Iversen, and S. H. Synder). Volumes such as these serve to usefully review the available litera ture without attempting a critical appraisal of the utility and limitations of methods and the difficulties of interpreting empirical data. Such conceptual and methodological problems are now an issue of paramount importance in studying the behavioral effects of drugs. The present volume can be regarded as a "conceptual cookbook" that examines the utility and limitations of various experimental approaches commonly taken in psychopharmacology. This practically oriented text should prove particularly useful for pharmacologists and neurochemists who have no formal training in behavioral research and require an intro duction to the actuallaboratory practice of the field. In addition, the useful and informative treatment of current issues in psychopharmacology will undoubtedly appeal to the majority of active researchers."

This compelling volume provides a broad and accessible overview on the rapidly developing field of social neuroscience. A major goal of the volume is to integrate research findings on the neural basis of social behavior across different levels of analysis from rodent studies on molecular neurobiology to behavioral neuroscience to fMRI imaging data on human social behavior.

This book begins the discourse on post-trial access to drugs in developing countries. Underlying ethical issues in global health inequalities and global health research serve as the context of the debate. Due to rampant allegations of violations of rights of research participants, especially in developing countries, it discusses the regulatory infrastructure and ethical oversight of international clinical research, thus emphasizing the priority of safeguarding the rights of research participants and host populations as desiderata in conducting clinical trials in developing countries. This is the first book that analyzes the major obstacles of affordable access to drugs in developing countries - patent and non-patent factors and how they can be overcome through a middle ground approach and a new paradigm to establish global health justice which includes national and global health responsibilities. The book also deals extensively with all complex aspects of the discourse on affordable access to drugs in developing countries, including intellectual property law, international regulations, political and cultural systems, international trade agreements. Furthermore it contains a robust ethical debate and in-depth analysis. The book crafts a paradigm of global health justice involving a sliding scale of national and global responsibilities for the realization of the right to health in general and access to drugs in particular.

This authored book presents basic immunological tenets and mechanisms at the cellular and molecular level while employing the toxicology focus on hazard identification, appropriate assays, dose response, and risk assesment by mathematical models and safety factors. It will be a useful reference to toxicologists because it will incorporate new guidelines that the EPA is bringing out later this year for all chemicals regulated under the Federal Insecticide, Fungicide, and Rodenticide Act and the Toxic Substances Control Act. Regulatory sections in each chapter focus on data from both the US Food and Drug Administration, as well as data applicable to western European Nations.

A collection of challenging and unusual cases from the author's extensive experience as a Medical Toxicologist, these cases demonstrate medical problem solving and differential diagnosis in action from the perspective of an experienced clinician. Written in an engaging style and giving a fascinating account of some complex cases from real practice, this book will provide a good supplementary learning text for graduate students or those at an early stage in their professional career.

Immunopotentiators in Modern Vaccines, Second Edition, provides in-depth insights and overviews of the most successful adjuvants, those that have been included in licensed products, also covering the most promising technologies that have emerged in recent years. In contrast to existing books on the subject, the chapters here provide summaries of key data on the mechanisms of action of the individual vaccine adjuvants. In addition, the book covers key aspects of how the technologies might be further developed and what might be their limitations, while also giving an overview of what made the most advanced adjuvant technologies successful.

The many drawbacks of conventional dosage forms and delivery systems are overcome by designing and developing controlled release drug delivery systems, and pharmaceutical and other scientists have carried out extensive and intensive investigations in the field to explore their applications. A controlled-release drug formulation can improve product efficacy and extend patent protection. As controlled drug delivery systems continue to play a vital role in delivering various types of therapeutic agents in a controlled manner, researchers are only just scratching the surface of their full potential. Advancements in Controlled Drug Delivery Systems supplies information on translating the physicochemical properties of drugs into drug delivery systems, explores how drugs are administered via various routes, and discusses recent advancements in the fabrication and development of controlled drug delivery systems. It also underlines the methodology of controlled drug delivery system preparation and the significance, disadvantages, detailed classifications, and relevant examples. Covering topics such as machine learning and oral-controlled drug delivery, this book is ideal for pharmacists, healthcare professionals, researchers, academicians, research centers, health units, students, and pharmaceutical and scientific laboratories.

This detailed volume assembles comprehensive protocols to assist with the study of structural, molecular, cell biological, and in vivo facets of GPCRs, and to enable the development of experimental tools for screening novel GPCR drugs. Sections explore the tweaking of ligands, bioluminescence and FRET approaches, specific GPCR signaling properties, as well as visualization of subcellular compartmentalization. Written for the highly successful Methods in Molecular Biology series, 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. Authoritative and practical, G Protein-Coupled Receptor Signaling: Methods and Protocols serves as an ideal reference for life scientists working in a variety of research fields including molecular pharmacology, cell and developmental biology, brain behavior and physiology, drug development and screening. Chapter 4 is available open access under a CC BY 4.0 license via link.springer.com.

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.

In transfusion medicine the scientific fundamentals of immunology have had a considerable clinical impact. Transfusion may suppress the immunity but some patients could suffer disadvantages including GvHD, alloimmunisation and possible cancer, where white cells (WBC) play pivotal roles in this phenomenon, presenting antigens and producing cytokines. A clinical application of this practice is LAK-cells targeted against cancer. MHC on the WBC may provide additional immunological modulations through series of secondary messengers. Thus reduction of WBC in the blood and bone marrow may be advantageous for patients. On the other hand, sharing a part of MHC or making the transplanted white cells anergic by storage may be even more advantageous for patients. CMV infection could mimic part of this MHC. UV radiation is effective in the inactivation of the WBC although filters are easy means for such removal. However, their accurate quantification requires flow cytometry that has considerable potential application in blood transfusions. Idiotypic antibody could play an important role in platelet theory. However, the potential infection risks in transfusion like HIV and HCV remain, but application of molecular biological methods like PCR or RT/PCR has great potentials in detection of infectious diseases, transplantation and genetic disorders. Immuno affinity purified concentrates, like factor IX and protein C, could reduce patients' immune functions, where in the future protein C could be derived from transgenic animals. Advances are sure to emerge through adoptive immunotherapy and gene therapies are exciting prospects when genes transferred into lymphocytes could be used to correct cell mediated immune deficiency, as in ADA.

This book serves as a reference volume for anyone interested in nicotine and tobacco. An international team of authors contribute to this comprehensive review of current knowledge on the pharmacokinetics and metabolism of nicotine. A broad range of material on the action and uptake of nicotine and the consequences of exposure to it has been drawn together for the first time in this volume. This book should be of interest to research scientists and health professionals in pharmacology, toxicology and neurosciences.

The specific topic, "Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants - New Perspectives In Parkinson`S Disease Therapy," was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinson`s disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): ss-carbolines (BCs) and tetrahydroisoquinolines (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances. In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties. Additionally, the recent results of experimental studies in vivo have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility of their therapeutic applications in neurodegenerative diseases such as Parkinson's disease.

Valproic acid was first synthesized in 1882 by Burton, but there was no known clinical use until its anticonvulsant activity was fortuitously discovered by H. Meunier in 1963 in the laboratory of G. Carraz. The first clinical trials of the sodium salt of valproate were reported in 1964 by Carraz. It was marketed in France in 1967 and was released in the United States in 1978 for the treatment of epilepsy. Since then, valproate has established itself worldwide as a major antiepileptic drug against several types of seizures. Clinical experience with valproate has continued to grow in recent years, including use of valproate for diseases other than epilepsy, for example in bipolar disorders and migraine. In this book, emphasis is placed on the scientific background leading to the discovery of valproate and its clinical development into one of the most widely and successfully used antiepileptic drugs, a real milestone in drug therapy. The current state of knowledge of valproate is reviewed by experts in the field, including new hypotheses on its mechanisms of action, its metabolism into pharmacologically active metabolites, its unique distribution characteristics, its undesirable hepatotoxic and teratogenic adverse effects, and its various clinical uses. The monograph is aimed at a broad readership, particularly neurologists, psychiatrists and basic scientists working in the field of epilepsy research. Furthermore, the book also deals with structure-activity relationships of valproate as well as of its metabolites and analogs and should therefore attract researchers working in medicinal chemistry.

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

What drives a scientist to edit a book on a speci c scienti c subject such as chiral mechanisms in separation methods? Until December 2005, the journal Analytical Chemistry of the American Chemical Society (Washington, DC) had an A-page section that was dedicated to simple and clear presentations of the most recent te- niques or the state of the art in a particular eld or topic. The "A-page" section was prepared for a broad audience of chemists including industrial professionals, s- dents as well as academics looking for information outside their eld of expertise. 1 Daniel W. Armstrong, one of the editors of this journal and a twenty-year+ long friend, invited me to present my view on chiral recognition mechanisms in a simple and clear way in an "A-page" article. In 2006, the "A-page" section was maintained as the rst articles at the beginning of each rst bi-monthly issue but the pagination was no longer page distinguished from the regular research articles published by the journal. During the time between the invitation and the submission, the A-page section was integrated into the rest of the journal and the article appeared as (2006) Anal Chem (78):2093-2099.

With the increasing interest in the experimental and clinical application of molecular imaging many institutions create research groups or interdisciplinary centers focussing on the complex development process of this new methodology. The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is beeing addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation.

This volume presents a broad compendium of techniques used in biodegradation and toxicological research. Through both legacy and up-to-date approaches to practical methodologies with proven results, the book examines the role and applications of analytical biodegradation quantification as it applies to the environmental sciences, particularly in the range of byproducts that are usually linked to toxicology, and the test organisms most often used in toxicity testing. Topics include scientific and technical feasibility studies, contaminant impacts evaluation, study design and analytical techniques, key methodologies required to prepare the biodegradation and toxicology protocols, as well as the handling of microbial communities related to such processes. Written for the Methods in Pharmacology and Toxicology series, chapters deal with a critical discussion of laboratory scale experiments, as well as full scale in situ and ex situ apparatus, with each chapter containing both a discursive section along with a detailed methods section. Detailed and authoritative, Toxicity and Biodegradation Testing is primarily focused toward the environmental sciences researcher, while the range of techniques also provides an introduction to biodegradation and toxicology methods for researchers outside of the field.

The contents of this book will be organized into three sections. The first section defines the scope, impact and behaviour of cancer regimen-related toxicities and frames the issue of balancing treatment success and physiological cost. In the second segment of the book, the most current thinking around the pathobiology of specific, common, and representative toxicities is presented by leading researchers and translational scientists. The final portion of the book discusses the common biological relationships between toxicities, bioinformatical approaches to analysing key and common pathways, and strategies for the development of effective interventions.

This innovative volume introduces Trajectory Analysis, a new systems-based approach to measuring nonlinear dynamics in continuous change, to public health and epidemiology. It synthesizes influential strands of statistical and probability science (including chaos theory and catastrophe theory) to complement existing methods and models used in the health fields. The computational framework featured here pinpoints complex cause-and-effect processes in behavioral change as individuals and populations adjust to health interventions, with examples from neuroscience and cardiology. But this is no mere academic exercise, as the author illustrates how these methods can be harnessed toward finding real-world answers to longstanding public health problems, starting with treatment recidivism. Included in the coverage: * The universality of physical principles in the analysis of health and disease * The problem of recidivism in healthcare intervention studies * Stability and reversibility/irreversibility of health conditions * Chaos theory and sensitive dependence on initial conditions * Applications in health monitoring and geographic systems * Simulations, applications, and the challenge for public health A stimulating new take on statistics with powerful implications for future study, practice, and policy, Trajectory Analysis in Health Care should interest public health epidemiologists, researchers, clinicians, and policymakers.

The aim of this book is to present a range of analytical methods that can be used in formulation design and development and focus on how these systems can be applied to understand formulation components and the dosage form these build. To effectively design and exploit drug delivery systems, the underlying characteristic of a dosage form must be understood--from the characteristics of the individual formulation components, to how they act and interact within the formulation, and finally, to how this formulation responds in different biological environments. To achieve this, there is a wide range of analytical techniques that can be adopted to understand and elucidate the mechanics of drug delivery and drug formulation. Such methods include e.g. spectroscopic analysis, diffractometric analysis, thermal investigations, surface analytical techniques, particle size analysis, rheological techniques, methods to characterize drug stability and release, and biological analysis in appropriate cell and animal models. Whilst each of these methods can encompass a full research area in their own right, formulation scientists must be able to effectively apply these methods to the delivery system they are considering. The information in this book is designed to support researchers in their ability to fully characterize and analyze a range of delivery systems, using an appropriate selection of analytical techniques. Due to its consideration of regulatory approval, this book will also be suitable for industrial researchers both at early stage up to pre-clinical research.

In her thesis, Sara Bobone outlines spectroscopic studies of antimicrobial peptides (AMPs) which are promising lead compounds for drugs used to fight multidrug resistant bacteria. Bobone shows that AMPs interact with liposomes and she clarifies the structure of pores formed by one of these molecules. These results help us to understand how AMPs are selective for bacterial membranes and how their activity can be finely tuned by modifying their sequence. Findings which solve several conundrums debated in the literature for years. In addition, Bobone uses liposomes as nanotemplates for the photopolymerization of hydrogels - exploiting the self- assembly properties of phospholipids. Bobone was able to trap an enzyme using nanometeric particles, while still allowing its activity by the diffusion of substrates and products through the network of the polymer. The innovative nano devices described in this thesis could solve many of the hurdles still hampering the therapeutic application of protein-based drugs.

Only a few years ago the endocannabinoid system was unknown. Today we are aware that endocannabinoids are involved in many of the functions of the mammalian body - in neuroprotection, appetite and suckling, pain, reproduction, anxiety, memory, bone formation etc. This volume presents an up-to-date picture of some of the major fields of endocannabinoid research. It summarizes the actions of the endocannabinoids on various physiological systems and opens new therapeutic windows to a large number of diseases. The first chapter, on the use of Cannabis in India, can be viewed as an expression of thanks to the herbal practitioners, who for centuries passed on the medical traditions associated with the drug. The chapter on chemistry is a short summary of active plant, synthetic and endogenous cannabinoids being investigated today, many of which are mentioned later in the book. Cannabidiol is an unusual cannabinoid - it does not bind to the known receptors and yet exerts a variety of effects. Hence a chapter is devoted to it. Further chapters deal with the endocannabinoid system and the endocannabinoids in a variety of conditions and physiological systems. The concluding chapter describes the research done on Sativex (R), a standardized plant extract, shortly to be introduced in Canada as a drug for multiple sclerosis. The intended audience is drug researchers (medicinal chemists, pharmacologists, clinicians), neuroscientists, physiologists, and clinicians interested in the effect of the endocannabinoid system in various physiological systems.