This book provides multidisciplinary reviews of the mechanism of action and uses of methotrexate in the treatment of cancer, psoriasis, gynecologic and inflammatory diseases. The intended audience is composed of clinicians involved in the care of patients suffering from oncologic, gynecologic, rheumatic diseases as well as scientists involved in research into the pathogenesis and treatment of these diseases. This book is unique in that it provides a single, state-of-the-art source for information regarding the mechanism and use of methotrexate in many different areas of medicine.

The role that placebos play in many treatments is clear: they not only play a complimentary role in various treatment options but they can sometimes be the only beneficial option for treatment. Brain imaging studies over the past decade have shown that placebo-treated patients undergo some of the same changes in brain activity as those treated with pharmacologically active substances. Yet this important component of healing is not yet harnessed in clinical settings. The Placebo Effect in Clinical Practice brings together what we know about the mechanisms behind the placebo response, as well as the procedures that promote these responses, in order to provide a focused and concise overview on how current knowledge can be applied in treatment settings. An introductory chapter documents the ubiquity and extent of the placebo response and discusses the history of the placebo response in relation to medical treatment. Several subsequent chapters focus on how placebos work and how the placebo effect can be enhanced. Expectation, conditioning and elements of the treatment situation are covered in separate chapters. The relationship between psychotherapy and placebo treatment is covered as is the ethics of deliberate use of the placebo effect. Because placebo effects are particularly prominent in some psychiatric conditions, particular attention is given to the role of the placebo response in psychiatric treatment. The final chapter summarizes what we currently know and offers concrete suggestions for how what we know of the placebo effect can be used to enhance the benefit of all treatments.

Classical natural product chemistry is transitioning to modern day metabolomics as a result of the advent of comprehensive analytical platforms and sensitive analytical instrumentation. Therefore, it is worthwhile to summarize recent developments with current analytical platforms and highlight how metabolomics is being integrated into this classical field to dereplicate and profile natural product extracts. Metabolomics Tools for Natural Product Discoveries: Methods and Protocols aims to unite diverse and recently developed methodologies and protocols in order to identify bioactive secondary metabolites for the purpose of drug discovery. Some topics covered in this volume include applications for the extraction of selected natural products from less common sources such as bryophytes and hard corals, various biological assays, comprehensive applications and strategies for GC-MS, LC-MS, and NMR, as well as protocols and strategies for the structure elucidation of isolated natural products. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible Metabolomics Tools for Natural Product Discoveries: Methods and Protocols seeks to serve both professionals and research students with its well-honed methodologies for natural product isolation, biomarker discovery, dereplication, biological assays, and comprehensive metabolomic platforms available for high-throughput analyses.

This book describes applications of acridines for the treatment of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and various prion diseases, and discusses the potential of acridines in neuro-regenerative medicine. Using modern data-mining software, it presents structures of acridines with nucleic acids and proteins and compares them with the native structures. Furthermore, the book presents modern methods of acridine synthesis, comparing them with the most useful conventional methods. Acridines interact with both nucleic acids and proteins, and due to their direct interactions with various enzymes, they can be suitable for the treatment of neurodegenerative diseases, inflammation, immunological disorders, and protozoal diseases. The characteristic spectral properties of acridines can be employed in labeling proteins, nucleic acids, lipids, and even cells and their compartments. Moreover, they can be applied in photodynamic therapy.

This book highlights the importance of the choroid plexus, which forms the blood-cerebrospinal fluid barrier and is the site of the major production of the cerebrospinal fluid (CSF). The authors show that this barrier is crucial for maintaining important compositional differences between the blood plasma and the CSF. The choroid plexus epithelial cells also prevent the spread of infectious agents and other blood-borne entities to the brain tissue. Chapter topics range from the production of CSF by electrolyte regulation in the choroid plexus, to details on the selectively transporting nature of this barrier. Further, the authors elaborate on the important roles of CSF in sustaining brain health by providing hydration, solutes, and nutrients to the brain tissue. Readers will also learn how CSF circulates signaling molecules within the compartments of the brain and removes waste products from the brain tissue. Elucidating the regulation of these processes in the choroid plexus is not only important for the readers' understanding of normal brain development and function, but is also crucial for resolving a variety of cerebral challenges that lead to brain edema, as well as developing treatments for diseases. The book discusses disease models like hydrocephalus, sleep disorders, and age-related dementia. Its comprehensive coverage makes this volume a valuable resource for researchers in cell and neurophysiology, as well as graduate students of the neurosciences.

The environment is prone to suffer pollution and toxic insult from generations of nanomaterials as well from accidental releases during production, transportation, and disposal operations. The NMs could interact with and cause adverse biological effects at cellular, subcellular, and molecular levels. Assessing potential environmental/ecological risks requires quality information on transport and fate of nanoparticles in the environment, exposures and vulnerabilities of organisms to the nanomaterials and standard methods for assessing toxicity for aquatic or terrestrial organisms and human health. The systematic risk characterization and evaluation of the safety of nanomaterials require a multidisciplinary approach and convergence of knowledge and efforts from researchers and experts from toxicology, biotechnology, materials science, chemistry, physics, engineering, and other branches of life sciences. Although studies are beginning to appear in the literature addressing the toxicity of various nanomaterials and their potential for exposure, at this stage definitive statements regarding the impacts of nanomaterials on human health and the environment remain sketchy requiring an increased level of precautions with regard to nanomaterials, as has happened with other emerging contaminants and technologies (e.g., biotechnology). The need for an increased level of understanding the perception of risk and of benefits will vary and is likely to influence public, regulatory, and non-governmental activities regarding risk and benefit evaluations. Systematic identification and assessment of the risks posed by any new technology are essential. A prudent, integrated, and holistic approach is required to develop best practices based on the scientific understanding about what we know and what we don't know but need to know. Nanomaterials addresses key issues of ecotoxicological actions and effects of nanomaterials on life and environment, their threats, vulnerability, risks, and public perception. The readers learn to read bad news objectively and think about and search for ecological 'green' solutions to current environmental and ecological problems with blue, grey, brown, and red shades for building a sustainable ecosystem. It shows how this molecular terrain is a common ground for interdisciplinary research and education that will be an essential component of science, engineering and technology in the future. The book is divided into three sections. Section I includes general topics related to ecotoxicity of nanomaterials to microbes, plants, human and environment. Section 2 incorporates risks generated by the use of nanomaterials. Section 3 discusss safety issues and the public.

The field of oligonucleotide therapeutics research is ripe with the prospect of new discoveries. In "Therapeutic Oligonucleotides: Methods and Protocols," a selection of established and emerging methods for the application of oligonucleotides as therapeutics are presented, all providing the tools needed to inspire great changes in the field. Divided into twenty-one chapters, this detailed volume meticulously describes vital protocols for optimizing and improving cell uptake, such as photochemical internalization, modified cell penetrating peptides, antibody conjugates, and nanoparticles. Other chapters address quantitation of RNA therapeutics in cells, assaying gene knockdown, selecting the best target site and synthesis of various modified oligonucleotides. Written in the successful "Methods in Molecular Biology " series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and easily accessible, "Therapeutic Oligonucleotides: Methods and Protocols "serves as a timely resource for both professionals and novices pursuing research in this exciting and pioneering field."

Dendritic Cells; J.M. Austyn. The Multiple Accessory Cell Concept; M. Van Rooijen. Sythetic Peptides and the Role of T-Helper Cell Determinants; M.J. Francis. Carriers for Peptides; M.J. Francis. Co-Entrapment of T-Cell and B-Cell Peptides in Liposomes Overcomes Genetic Restriction in Mice and Induces Immunological Memory; G. Gregoriadis, et al. Preparation and Characterization of Stable Liposomal Hepatitis B Vaccine; D. Diminsky, et al. Initiation of Immune Response with ISCOM; B. Morein, et al. Nanoparticles as Potent Aduvants for Vaccines; J. Kreuter. Optimization of Carriers and Adjuvants; A. Snidjders, et al. Immunotargeting as an Adjuvant Independent Subunit Vaccine Design Option; D.L. Skea, B.H. Barber. BCG Vaccine; M.J. Groves, et al. Significance of Virulence Factors and ImmunoEvasion for the Design of Gene-Deleted Herpesvirus Marker Vaccines; S. Kit. Eradication of Sylvatic Rabies Using a Live Recombinant Vaccinia-vRabies Vaccine; M.P. Kieny, et al. 7 additional articles. Index.

This book was conceived from a simple question as to why cancer is so difficult to treat. Ultimately we want to find ways to cure cancers, but that may be an elusive dream at least with the technologies we have now and expect to have in the near future. This leads the question of whether it is possible to improve current cancer treatment methods, especially from the perspective of enhancing targeted drug delivery to tumors. This volume is designed to provide information related to the difficulties in treating cancers through targeted drug delivery, our current understanding of cancer biology, and potential technologies that might be used to achieve enhanced drug delivery to tumors. An ideal drug delivery system for treating cancers would maximize the therapeutic efficacy with minimal side effects in clinical applications. The seemingly improved anticancer efficacy of the current nanoparticle-based formulations needs to be viewed from the context of very poor success rates for translation to human applications. The results of in vitro cell culture models and small animal in vivo experiments have not been extrapolated to clinical applications. Finding the reasons for the lack of successful translation is required if we are to discover approaches to substantially extend the survival time of cancer patients, and hopefully identify cures. Cancer Targeted Drug Delivery: Elusive Dream describes some answers of achieving the so far elusive dream of treating cancers like other chronic diseases with therapies that focus using improved drug delivery systems designed to better align with the unique biological and physiological properties of cancer.

This book explores pain in a number of ways. At the heart of the book is an extension of Melzack's neuromatrix theory of pain into the social, cultural, and economic fields. Specific assemblages involving varied institutions, flows of capital, encounters, and social and economic structures provide a framework for the formation of pain, its perception, experience, meaning, and cultural production. Complementing the extended neuromatrix is a second theory, focussed on the propensity of western market capitalism to seek out new areas of life to subsume to capital. Pain is one such life area that is now ripe for exploitation. Although the book has theory at its heart, it draws extensively on case studies to identify the contradictions and complexities. Case studies are drawn from accounts of drug use in varied contexts such as prescription drugs, methamphetamine use, oxycodone use in North America, and the global rise of the medicinal cannabis marketplace.

This book addresses the highly relevant and complex subject of research on drugs from natural products, discussing the current hot topics in the field. It also provides a detailed overview of the strategies used to research and develop these drugs. Respected experts explore issues involved in the production chain and when looking for new medicinal agents, including aspects such as therapeutic potential, functional foods, ethnopharmacology, metabolomics, virtual screening and regulatory scenarios. Further, the book describes strategic methods of isolation and characterization of active principles, biological assays, biotechnology of plants, synthesis, clinical trials and the use of tools to identity active principles.

The action of antimicrobial peptides (AMPs), ranging from direct killing of invading pathogens to immune response modulation and other complex biological responses, has stimulated research and clinical interest for more than two decades, but the area is still burgeoning due to emerging discoveries in the functions, roles, and regulation of AMPs, thus making the study of antimicrobial peptides a multi-disciplinary and rapidly evolving field. In Antimicrobial Peptides: Methods and Protocols, leading investigators present a broad, up-to-date collection of current research and experimental methods for the isolation, characterization, production, and optimization of antimicrobial peptides. Additional chapters detail methodologies in several microscopy techniques, high-throughput screening, QSAR modeling, and computer-aided design used to study these compounds, while key review articles survey potential medical applications of antimicrobial peptides as innovative anti-infective and immunomodulatory agents, as well as emerging discoveries in their function, regulation, and roles in innate immunity. As a volume in the highly successful Methods in Molecular Biology (TM) series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and wide-ranging in its applications, Antimicrobial Peptides: Methods and Protocols provides both an authoritative guide for lab work on AMPs or related substances and a useful collection of thought stimuli to inspire further scientific endeavours in a wide array of vital fields.

Psychophysiology is an ever expanding field. The application of psychophysiological investigations to psychiatric disorders is likewise expanding and has in fact shed much light on some of the neural processes contributing to the development of psychiatric symptoms and/or their amelioration following treatment. In the first part of this volume, we have selected a number of conditions where psychophysiological investigations have recently provided some insight into the pathophysiology of a particular manifestation (e.g., dissociation) or a disorder. Although this volume has a main focus on electrophysiological investigative modalities where neuroimaging was complimentary this added insight was included. The second part of the volume focuses on novel uses of psychophysiological measures, combining it with neuropsychology and imaging where possible, in the context of neuropsychiatric research and describes advanced analytical tools. Both basic and clinical investigators in this field should find the reviews and interpretations provided clear and informative. Clinicians will find this volume easy to assimilate. While direct clinical applications may be down the road, the insights provided should help the practicing clinicians to have firmer understanding of the complexity of the disorder they manage in everyday practice.

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.

This second edition volume expands on the first edition by providing up-to-date protocols to characterize nanomaterials used as drug delivery agents. The chapters in this book are divided into 5 parts and cover topics such as: advances and obstacles in nanomedicine research; methods to test sterility and endotoxin, physicochemical features, immunological effects, drug release, and in vivo efficacy. Written in the highly successful Methods in Molecular Biology series format, 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. Cutting-edge and comprehensive, Characterization of Nanoparticles Intended for Drug Delivery, Second Edition is a valuable tool for researchers and pharmaceutical and biotechnology developers who are evaluating the clinical potential of nanomedicines in preclinical studies.>

Primary care clinicians are called on to care for adolescents in a time with increasing pharmacologic agents that are available in the management of these patients. The emphasis in this book is on the current pharmacologic treatment of common medical disorders in adolescents. Selected topics of practical relevance in adolescent medicine are covered. The goal of this book is to provide a succinct and practical guide specifically written for practicing physicians and allied health professionals who work with adolescents.

Microbial Phenazines: Biosynthesis, Agriculture and Health focuses on phenazines, a group of upwards of a hundred nitrogen-containing redox-active heterocyclic compounds of bacterial origin that have long attracted scientific interest because of their colorful pigmentation. Our understanding of these fascinating natural products and their role in human health and the environment has advanced rapidly in recent years, but we are only now beginning to be able to exploit the potential of these compounds in such fields as agriculture and medicine. This volume includes information on the biochemistry and genetics of phenazine synthesis, the physiological effects of phenazines, and methods for the isolation and identification of phenazines with the aid of spectroscopic and electrophoretic techniques. Also included are chapters focused on the roots of phenazine research in the biological control of plant pathogens and recent knowledge of the diversity of phenazine-producing microorganisms and the environments in which they occur. A final chapter addresses the potential of phenazines in the treatment of cancer.

With genetic engineering, systems explored in this book now exist allowing for the simple, efficient, and near universally precise genetic manipulation directly in any organism, including the mouse. Herein, these models are applied to a wide field of disease areas, including diabetes, cardiovascular disease, skin disorders, cancer, neurodegenerative and neuromuscular diseases, retinal disorders, as well as various behavioral models. 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. Practical and fully updated, Mouse Models for Drug Discovery: Methods and Protocols, Second Edition serves to equip the reader with an extensive overview of techniques to utilize the many possibilities of mice in the drug development process.

Epigenetics has emerged recently as an important area of molecular biological studies. Epigenetic modifications lead to potentially heritable but reversible alterations in the expression of genes that determine cell fate. Epigenetic misregulation is thus often linked to degenerative diseases, cancer and neuronal disorders. Recent biomedical interest in this regulatory system stems from the fact that epigenetic, in contrast to genetic, alterations are in principle amenable to pharmacological intervention. A few epigenetically active drugs, for example histone deacetylase inhibitors (HDACi) and DNA methyltransferase (DNMT) inhibitors, have been approved by FDA for treatment of cancers such as CTCL, MDS, and AML. This volume explores the scientific background for clinical applications of epigenetically active drugs. Included are descriptions of epigenetic controls over gene expression, the post-transcriptional silencing of genes by RNA interference (RNAi) and microRNAs, as well as new findings from stem cell research which are relevant to pharmacological applications. Content Level Research

In this volume we will cover technologies and associated methodologies that allow identification, characterization and application of therapeutic peptides.

The section covering identification will cover areas such as display on the surface of filamentous or lytic phage, substrate phage display, ribosome display and the use of peptide library pools.

Often the output from library selection is not a peptide but the sequence of a peptide. We will therefore discuss approaches to produce peptide ligands both synthetically and through recombinant techniques. This section will also include a discussion of how peptides may be produced such that their serum residence time can be extended to allow weekly dosing such as fusions to other larger proteins or through modification with PEG.

The next section covers biophysical tools for characterization of peptide interactions with proteins. These include fluorescence polarization, equilibrium dialysis, radioligand binding assays, regular and array based SPR analysis.

The remaining section outlines methods for preparation and application of peptides as: imaging agents; targeting agents for radionuclei; receptor antagonists, and as tools to mediate cell penetration

This practical volume examines a number of topics that explore the current status of immunotherapy and diagnostic markers for neurodegenerative disorders. With a focus on Alzheimer's disease, the first sections of the book examine immunotherapeutic approaches for the aforementioned disease as well as for Parkinson's disease and Huntington's disease, amongst others. The last section of the book covers the importance of biomarker techniques to catch these diseases early enough for the treatments to be most useful. Written for the Methods in Pharmacology and Toxicology series, this book contains the kind of detailed descriptions and implementation advice that will offer a smooth transition into the lab. Authoritative and useful, Immunotherapy and Biomarkers in Neurodegenerative Disorders aims to aid in the continued progress in the development of novel immune-based drugs and diagnostic tools for these devastating brain diseases.

This book would combine chapters written by the most qualified authors around the world whose research encompasses the effect of morphine or other opioids on tumor growth and metastasis. This includes clinicians involved in trials determining which type of post surgical pain management can minimize the risk of recurrence or metastasis, researchers working on animal models and studying the effect of morphine on tumors, and most importantly the mechanism for this effect, and lastly cell biologists. There is currently a lot of research going on trying to reconcile the pro- and anti-cancer aspects of opioids actions.

The primary purpose of this book and its companion volume The Neuropharmacology of Nicotine Dependence is to explore the ways in which recent studies on nicotine and its role in tobacco addiction have opened our eyes to the psychopharmacological properties of this unique and fascinating drug. While the present volume considers the molecular and genetic factors which influence behavioral responses to nicotine and how these may impact on the role of nicotine in tobacco dependence, the book The Neuropharmacology of Nicotine Dependence focuses on the complex neural and psychological mechanisms that mediate nicotine dependence in experimental animal models and their relationship to tobacco addiction in humans. These volumes will provide readers with a contemporary overview of current research on nicotine psychopharmacology and its role in tobacco dependence from leaders in this field of research and will hopefully prove valuable to those who are developing their own research programmes in this important topic.