Pain and inflammation are inextricably linked phenomena. The observation that chemical mediators with combined pro-inflammatory, algesic and/or hyperalgesic activity occur at the site of inflammation is fundamental not only to our present understanding of the inflammatory process but also to our attempts to devise clini- cally useful anti-inflammatory therapies. Over a hundred years ago it was recognised that primary sensory neurones play a crucially important "dual" role in inflammation. By affecting the transfer of infor- mation from peripheral nociceptors to the spinal cord, a subpopulation of sensory nerves {"pain fibres"} initiate algesia and hyperalgesia, whose sensations are then modified and fine-tuned in the central nervous system. Equally important is the release from the peripheral terminals of sensory neurones of neuropeptides, the acute effects of which are observed as changes in microvascular tone and perme- ability leading to neurogenic inflammation. Over the last decade it has become increasingly clear that this view of the func- tion of sensory nerves is somewhat over-simplified. For example, the mechanisms underlying hyperalgesia may, in certain circumstances, be mimicked in other condi- tions such as the hypersensivity associated with asthma. Furthermore, it has become increasingly evident that over a longer time period the release of neuropeptides from peripheral sensory nerve endings may also have modulating effects on inmune cells and that this may be relevant to chronic inflammatory disease and possibly also to inflammatory hyperalgesia.

"Practical Utility of Biomarkers in Drug Discovery and Development" covers all aspects of biomarker research applied to drug discovery and development and contains state-of-the-art appraisals on the practical utility of genomic, biochemical, and protein biomarkers. Case histories and lessons from successful and unsuccessful applications of biomarkers are included along with key chapters on GLP validation, safety biomarkers and proteomics biomarkers. Regulatory agency perspectives and initiatives both in the US and internationally are also discussed.

Polymers continue to show almost amazing versatility. We have always known that polymers could be used for trinkets, toys and dishes. Now, however, we are no longer surprised to encounter these adaptable mate rials in almost every place we look. We find them in our cars, tools, electronic devices, building materials, etc. The use of polymeric mate rials in medicine is also well documented in previous books by one of the Editors (Gebelein) and by others. Likewise, the use of polymeric mate rials in pharmaceutical applications, especially in controlled release systems, is also well established. Nevertheless, the use of these ubiquitous chemicals is far less ob vious in the field of cosmetics, although modern cosmetic preparations rely heavily on polymers and this trend is certain to increase. This book brings together much of the basic information on polymers in cosmetics and compares this usage with similar applications in pharmaceutical and medical applications. Cosmetics, like medicine and pharmacy, dates back to antiquity. We can find uses of perfumes, balms and ointments in various old books, such as the Bible. For example, the use of ointments and balms is noted more than thirty eight times, and perfumes and related materials are cited at least twenty nine times in the Bible."

This book arises from a workshop organized by the American Association of Pharmaceutical Scientists entitled "Optimizing the Drug-Like Properties of Leads in Drug Discovery," which took place in Parsippany, NJ in September 2004. The workshop focused on the optimization of the drug-like properties of leads in drug discovery. The volume outlines strategies and methodologies designed to guide pharmaceutical and biotechnology companies through the drug discovery and development process.

Recent years have seen enormous advances in the field of protein and peptide engineering and a greater understanding in the way in which biological response modifiers function in the body. It is now possible through the use of recombinant DNA techniques, or by solid phase protein synthesis, to produce significant quantities of a wide variety of regulatory agents that are therapeutically applicable. The list of these response modifiers expands almost daily to include interferons, macrophage activation factors, neuropeptides and agents that may have potential in cardiovascular disease, inflammation, contraception etc. Prospects to use some of these materials in medicine have reached the stage where products have either been approved by regulatory authorities or are the subject of applications as investigatory drugs or as new therapeutic agents. In some uses the pertinent agent will be administered on an acute basis in the form of a simple injection, as, for example, the use of a tissue plasminogen activator for the treatment of coronary infarct. In other cases regulatory proteins and peptides are indicated for chronic therapy and here they will need to be administered by an appropriate delivery system. Unfortunately, the research on delivery systems for peptides and proteins has not kept pace with the rapid progress in biotechnology and, consequently, there are presently few systems that are entirely appropriate for the administration of macromolecular drugs according to complex dosage regimens, (eg intermittent and pulsed therapy). Furthermore essential pharmacokinetic and pharmacodynamic data may be missing.

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).

In Clinical Pharmacology of Cerebral Ischemia, a distinguished international panel of authors define our current understanding of neuronal damage after ischemia and critically review the significant recent progress in cerebrovascular accident (CVA) drug trials, both for animal models and in the clinical setting. These leading basic science and medical authorities survey such important new drugs as calcium-influx inhibitors, free-radical scavenging drugs, glutamate and glycinergic antagonists, and immune suppressors. They also evaluate all the latest findings concerning calcium homeostasis, glutamate toxicity, gene activation, and the role of free radicals, glycine, and hormones. Chapters devoted to the neuroimaging of stroke, clinical trials, and the role of cerebral immune activation complete this informative collection of cutting-edge reviews.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

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."

Ligand-gated ion channels mediate fast synaptic transmission in the central nervous s- tem (CNS) and at ganglionic and neuromuscular synapses. The nicotinic acetylcholine - ceptor (nAChR) is a member of the ligand-gated ion channel superfamily, which includes the 5-HT , glycine and GABA type A and C receptors. These receptors are known as Cys- 3 loop receptors, as all of them have a conserved sequence containing a pair of cysteines separated by 13 residues and linked by a disulfide bridge. nAChRs can be divided into two groups: muscle receptors, which are found at the skeletal neuromuscular junction where they mediate neuromuscular transmission, and neuronal receptors, which are found throughout the peripheral and central nervous system. Many of the early studies carried out on the subunit composition and structure of the nAChRs were performed on receptors isolated from the electric organ of Torpedo californica, as this tissue is very rich in nAChRs, and they were found to have a high degree of homology with the embryonic v- tebrate muscle type receptor. Muscle nAChRs are made up of five subunits arranged around a central pore (Fig. 1A, B). In Torpedo electric organ and vertebrate fetal muscle, the subunit composition is (a1) b1gd, and in adult muscle the g subunit is replaced by the e to give an (a1)b1ed 2 2 composition (Mishina et al. 1986).

This volume explores the considerable efforts that have been directed towards the development of G Protein-Coupled Receptors (GPCR) screening assays in order to disclose GPCR acting compounds, elucidate signaling mechanisms or evaluate compound's efficacy. New discoveries in the field, along with the widely recognized need for better and safer pharmaceutical drugs constitute the main motivation for this book. Readers, both beginners and experienced researchers, will receive an updated overview of not only the established, but also the innovative technologies that promise to advance GPCR drug research. This book is organized into two major parts: the introductory part discusses the necessary foundations for the understanding of GPCR action and the rationale behind the design of the available screening assays; and part two provides detailed protocols for different screening approaches. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Practical and innovative, G Protein-Coupled Receptor Screening Assays: Methods and Protocols reaches out to everyone involved in the discovery of GPCR-active drugs, and provides a transversal overview of the different levels of GPCR signaling addressable in the different screening strategies and presents practical examples of how current assay technologies are contributing to new paradigms in GPCR drug research.

Hypericum extract preparations are used extensively in many countries to treat mildly to moderately depressed patients. While this was based previously on traditional experience, extensive research over the last 10 years has given a broad preclinical and clinical basis to justify the use of Hypericum as an antidepressant. This book reviews the available data related to the biochemical, functional, and behavioural pharmacology of Hypericum and its active constituents. The clinical chapters overview the evidenced basis for its use as an antidepressant, initial data in anxiety and somatoform disorders, and the site effect profile of Hypericum and its possible relevant drug interactions. The known pharmacokinetics of the relevant constituents and the biopharmaceutical quality of commercially available Hypericum preparations are also discussed.

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.

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.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

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.

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.

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.

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 detailed book arrives as there is an increasing need for multiplex biomarker readouts for improved clinical management and to support the development of new drugs by pharmaceutical companies, due to continuous technical developments and new insights into the high complexity of many diseases. Chapters explore the basic technology platforms being applied in the fields of genomics, proteomics, transcriptomics, metabolomics, and imaging, which are currently the methods of choice in multiplex biomarker research. The book also describes the chief medical areas in which the greatest progress has been made and highlight areas where further resources are required. Written for the highly successful Methods in Molecular Biology series, methodology 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. Multiplex Biomarker Techniques: Methods and Applications serves as an ideal resource for a wide variety of researchers interested in these vital multiplex techniques.