Behcet's syndrome can reasonably be considered a unique entity among diseases of the immune system for several reasons: It has specific features and, uniquely among the immune system pathologies, represents a link between autoimmune diseases, systemic vasculitis, and autoinflammatory diseases. In addition, it is of interest to a variety of specialists, including immunologists, rheumatologists, dermatologists, and ophthalmologists, and requires a complex multidisciplinary approach. Many aspects need to be considered in a syndrome that presents a wide spectrum of symptoms and for which the therapeutic armamentarium is expanding significantly, with the development of new treatments, not least the so-called biologics. This book offers comprehensive coverage of the disease by some of the world's leading experts in Behcet's syndrome from all the relevant specialties. Epidemiology, genetics, pathogenesis, organ system involvement, differential diagnosis, novel treatments, surgical management, and prognosis are just some of the topics addressed. Behcet's Syndrome: From Pathogenesis to Treatment will be an invaluable reference for a range of practitioners, researchers, and undergraduates or postgraduates interested in immuno-rheumatology, dermatology, and rare diseases.

Transporters in Drug Development examines how membrane transporters can be dealt with in academic-industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of in vitro characterization of single transporters in the intestines, liver and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters' impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process.

The development of new CNS drugs is notoriously difficult. Drugs must reach CNS target sites for action and these sites are protected by a number of barriers, the most important being the blood -brain barrier (BBB). Many factors are therefore critical to consider for CNS drug delivery, e.g. active/passive transport across the BBB, intra-brain distribution, and central/systemic pharmacokinetics, to name a few. Neurological disease and trauma conditions add further complexity because CNS barriers, drug distribution and pharmacokinetics are dynamic and often changed by disease/trauma. Knowledge of all these factors and their interplay in different conditions is of utmost importance for proper CNS drug development and disease treatment. In recent years much information has become available for a better understanding of the many factors important for CNS drug delivery and how they interact to affect drug action. This book describes small and large drug delivery to the brain with an emphasis on the physiology of the BBB and the principles and concepts for drug delivery across the BBB and distribution within the brain. It contains methods descriptions for studying drug delivery, routes and approaches of administering drugs into the brain, the influence of disease, and drug industry perspectives. Therewith, it contributes to an in-depth understanding of the interplay between brain (patho)-physiology and drug characteristics. Furthermore, the content is designed to be both cutting-edge and educational, so that the book can be used in high-level training of academic and industry scientists with full references to original publications.

This volume provides readers with the basic principles and fundamentals of extrusion technology and a detailed description of the practical applications of a variety of extrusion processes, including various pharma grade extruders. In addition, the downstream production of films, pellets and tablets, for example, for oral and other delivery routes, are presented and discussed utilizing melt extrusion. This book is the first of its kind that discusses extensively the well-developed science of extrusion technology as applied to pharmaceutical drug product development and manufacturing. By covering a wide range of relevant topics, the text brings together all technical information necessary to develop and market pharmaceutical dosage forms that meet current quality and regulatory requirements. As extrusion technology continues to be refined further, usage of extruder systems and the array of applications will continue to expand, but the core technologies will remain the same.

In this book emphasis will be put in the relevance of Plant Biotechnology for producing compounds of pharmaceutical and industrial relevance specifically the contribution of in vitro plant cell cultures for producing recombinant proteins (molecular farming) and compounds produced by plants useful for human and animal health (secondary metabolites) will be discussed. Also the description of some process held by whole plants will be included. The aim will be to provide relevant theoretical frameworks and the latest empirical research findings for professionals and researchers working in the field of Plant Biotechnology, molecular farming and biochemical engineering.

Attention has recently turned to using plants as hosts for the production of commercially important proteins. The twelve case studies in this volume present successful strategies for using plants to produce industrial and pharmaceutical proteins and vaccine antigens. They examine in detail projects that have commercial potential or products that have already been commercialized, illustrating the advantages that plants offer over bacterial, fungal or animal cell-culture hosts. There are many indications that plant protein production marks the beginning of a new paradigm for the commercial production of proteins that, over the next decade, will expand dramatically.

One of the most promising new approaches for the prevention of HIV transmission, particularly for developing countries, involves topical, self-administered products known as microbicides. The development of microbicides is a long and complicated process, and this volume provides an overview of all the critical areas, from the selection of appropriate candidate molecules and their formulation, preclinical and clinical testing for safety and efficacy, strategies for product registration and finally, issues associated with product launch, distribution and access. The book will prove valuable to both those working in the field and all others who are interested in learning more about this product class, which has the potential to significantly impact the future of this devastating epidemic.

Specifically geared to personnel in the pharmaceutical and biotechnology industries, this book describes the basics and challenges of oral bioavailability one of the most significant hurdles in drug discovery and development. Describes approaches to assess pharmacokinetics and how drug efflux and uptake transporters impact oral bioavailability Helps readers reduce the failure rate of drug candidates when transitioning from the bench to the clinic during development Explains how preclinical animal models used in preclinical testing and in vitro tools translate to humans, which is an underappreciated and complicated area of drug development Includes chapters about pharmacokinetic modelling, the Biopharmaceutics Drug Disposition Classification System (BDDCS), and the Extended Clearance Classification System (ECCS) Has tutorials for applying strategies to medicinal chemistry practices of drug discovery/development

Volume III of this manual provides an overview of the analytical investigation of 23 additional Chinese Herbal Drugs, which are most commonly used in Traditional Chinese Medicine. Together with Volumes I and II this current volume represents the most comprehensive overview to analytical studies of those herbal drugs. The quality proof of the investigation meets the standard of the European Drug Regulatory Authority. The authors refer to the bioactive constituents, pharmacological and biological activities of all single herbal drugs, as well as their therapeutic applications. Analytical methods applied are described in detail.

This volume focuses on current evidence-based pharmacological treatments of various forms of pulmonary hypertension and provides a comprehensive review of the latest developments in this area. The first part of the book covers the definition, classification, pathophysiology, pathology, biomarkers and animal models of the disease, thus laying the conceptual basis for what follows. The middle section provides an overview of the established therapies, such as calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and inhaled nitric oxide. The last section explores novel pathways and emerging therapeutic approaches including soluble guanylate cyclase stimulators, Rho-kinase inhibitors, inhibitors of serotonin receptors and transporters, peptide growth factors, vasoactive peptides, modulators of redox equilibrium and cyclic nucleotide homeostasis, as well as immunosuppressive and anti-proliferative agents. Particular attention is given to the clinical applications of these experimental therapies, that are on the horizon. The book thus spans the continuum from basic science to clinical applications.

The author successfully developed novel anti-HIV PD 404182 derivatives that exhibited submicromolar inhibitory activity against both HIV-1 and HIV-2. His thesis is in three parts. The first part expounds efficient methods for the synthesis of tricyclic heterocycles related to PD 404182 based on the sp2-carbon−heteroatom bond formations. Starting from arene or haloarene, C-O, C-N, or C-S bonds were formed by simply changing the reactants. These synthetic methods provide powerful approaches for the divergent preparation of pyrimido-benzoxazine, -quinazoline, or -benzothiazine derivatives. The second part explains SAR studies of PD 404182 for the development of anti-HIV agents. Through optimization studies of the central 1,3-thiazin-2-imine core, the benzene and cyclic amidine ring parts, 3-fold more potent inhibitors were obtained compared with the lead compound. The author also reveals by a time-of-drug-addition experiment that PD 404182 derivatives impaired HIV replication at the binding or fusion stage. The third part of the thesis elucidates the development of photoaffinity probes for the target identification of PD 404182. By the photolabeling experiment of HIV-1-infected H9 cells using these probes, the author detected proteins specifically bound to PD 404182. These new anti-HIV agents may be promising agents for anti-HIV therapy because their mechanisms of action differ from those of the currently approved anti-HIV agents.

Covers the latest developments in UPLC and hyphenated techniques. Provides detailed coverage of sampling, sample handling, sample storage, and sample preparation. Expands coverage of Surface Analysis

Presents Practical Applications of Mass Spectrometry for Protein Analysis and Covers Their Impact on Accelerating Drug Discovery and Development * Covers both qualitative and quantitative aspects of Mass Spectrometry protein analysis in drug discovery * Principles, Instrumentation, Technologies topics include MS of peptides, proteins, and ADCs , instrumentation in protein analysis, nanospray technology in MS protein analysis, and automation in MS protein analysis * Details emerging areas from drug monitoring to patient care such as Identification and validation of biomarkers for cancer, targeted MS approaches for biomarker validation, biomarker discovery, and regulatory perspectives * Brings together the most current advances in the mass spectrometry technology and related method in protein analysis

This book presents a detailed overview of the development of new viral vector-based vaccines before discussing two major applications: preventive vaccines for infectious diseases and therapeutic cancer vaccines. Viral vector-based vaccines hold a great potential for development into successful pharmaceutical products and several examples at the advanced pre-clinical or clinical stage are presented. Nevertheless, the most efforts were focused on novel and very innovative technologies for new generation of vector-based vaccines. Furthermore, specific topics such as delivery and adjuvant and protection strategies for cell-mediated-based vaccines are presented. Given its scope, the book is a "must read" for all those involved in vaccine development, both in academia and industrial vaccine development.

The complexity of biological systems has intrigued scientists from many disciplines and has given birth to the highly influential field of systems biology wherein a wide array of mathematical techniques, such as flux balance analysis, and technology platforms, such as next generation sequencing, is used to understand, elucidate, and predict the functions of complex biological systems.  More recently, the field of synthetic biology, i.e., de novo engineering of biological systems, has emerged. Scientists from various fields are focusing on how to render this engineering process more predictable, reliable, scalable, affordable, and easy.  Systems and control theory is a branch of engineering and applied sciences that rigorously deals with the complexities and uncertainties of interconnected systems with the objective of characterising fundamental systemic properties such as stability, robustness, communication capacity, and other performance metrics. Systems and control theory also strives to offer concepts and methods that facilitate the design of systems with rigorous guarantees on these properties. Over the last 100 years, it has made stellar theoretical and technological contributions in diverse fields such as aerospace, telecommunication, storage, automotive, power systems, and others. Can it have, or evolve to have, a similar impact in biology? The chapters in this book demonstrate that, indeed, systems and control theoretic concepts and techniques can have a significant impact in systems and synthetic biology.  Volume I provides a panoramic view that illustrates the potential of such mathematical methods in systems and synthetic biology.  Recent advances in systems and synthetic biology have clearly demonstrated the benefits of a rigorous and systematic approach rooted in the principles of systems and control theory - not only does it lead to exciting insights and discoveries but it also reduces the inordinately lengthy trial-and-error process of wet-lab experimentation, thereby facilitating significant savings in human and financial resources.  In Volume I, some of the leading researchers in the field of systems and synthetic biology demonstrate how systems and control theoretic concepts and techniques can be useful, or should evolve to be useful, in order to understand how biological systems function.  As the eminent computer scientist Donald Knuth put it, "biology easily has 500 years of exciting problems to work on". This edited book presents but a small fraction of those for the benefit of (1) systems and control theorists interested in molecular and cellular biology and (2) biologists interested in rigorous modelling, analysis and control of biological systems.

In recent years, emerging trends in the design and development of drug products have indicated ever greater need for integrated characterization of excipients and in-depth understanding of their roles in drug delivery applications. This book presents a concise summary of relevant scientific and mechanistic information that can aid the use of excipients in formulation design and drug delivery applications. Each chapter is contributed by chosen experts in their respective fields, which affords truly in-depth perspective into a spectrum of excipient-focused topics. This book captures current subjects of interest - with the most up to date research updates - in the field of pharmaceutical excipients. This includes areas of interest to the biopharmaceutical industry users, students, educators, excipient manufacturers, and regulatory bodies alike.

This comprehensive text presents a rigorous framework from within which regulators can respond strategically to the claim by the pharmaceutical industry that lower drug prices today lead to a loss for the population's future health due to less innovation. It starts with a critical review of the empirical evidence of the return to consumers on their ongoing investment into high drug prices in order to increase future innovation. The implicit, critical and unrealistic assumption inherent in these studies is identified, namely that the health budget can be expanded to purchase drugs at higher prices without an opportunity cost, for example, the foregone benefits of alternative investments in health care infrastructure. Price effectiveness analysis (PEA), is introduced. PEA informs the question of how the innovative surplus from the new drug should be allocated between the manufacturer and the consumer so as to optimise society's welfare. The method allows the decisions by the regulator and the firm to be analysed jointly by specifying the firm's production and revenue functions in terms of the clinical innovation of a new drug; the incremental effect used in the summary metric of cost effectiveness analysis. An economic value of innovation that takes into account opportunity cost under conditions of economic efficiency in the health system is proposed: the health shadow price. The limitations of the non-strategic methods that currently inform the highly contested new drug subsidy game are presented and the relative strengths of PEA are demonstrated. Health technology assessment quantifies both the clinical innovation of a new drug and its financial impact on the health system. Cost effectiveness analysis tests the relationship between the incremental cost and incremental effect of a new drug for target patients, at a given price. PEA tests the relationship between the price of a new drug and the health of the whole population, now and into the future. It achieves this by taking into account current inefficiency in both resource allocation and the displacement process, and the relationship between price and future innovation.

In this book, clinicians and basic scientists from USA, India, and other countries discuss the rationales and clinical experiences with targeted approaches to treat, prevent, or manage cancer. Cancer is a hyperproliferative disorder that is regulated by multiple genes and multiple cell signaling pathways. Genomics, proteomics, and metabolomics have revealed that dysregulation of dozens of genes and their products occur in any given cell type that ultimately leads to cancer. These discoveries are providing unprecedented opportunities to tackle cancer by multi-faceted approaches that target these underpinnings. This book emphasizes a multi-targeted approach to treating cancer, the focus of the 5th International Conference on Translational Cancer Research that was held in Vigyan Bhawan, Delhi (India) from Feb 6-9, 2014.

Until the 1990s, it was generally accepted that medicines were first developed for adults and their use in children was investigated later, if at all. One of the main tasks of hospital pharmacies was the manufacturing of child-appropriate formulations in a more or less makeshift way. The first change came in 1997 with U.S. legislation that rewarded manufacturers to do voluntary pediatric research. Ten years later, the European Union passed legislation that required manufacturers to discuss all pediatric aspects, including formulations, with the regulatory authorities as a condition of starting the registration procedure. In consequence, manufacturers must now cover all age groups, including the youngest ones. So far, pediatric formulations were more a focus for academic researchers. Through the changed regulatory environment, there is now a sudden high commercial demand for age-appropriate formulations. This book begins by highlighting the anatomical, physiological and developmental differences between adults and children of different ages. It goes on to review the existing technologies and attempts to draw a roadmap to better, innovative formulations, in particular for oral administration. The regulatory, clinical, ethical and pharmaceutical framework is also addressed.

This introductory text explains both the basic science and the applications of biotechnology-derived pharmaceuticals, with special emphasis on their clinical use. It serves as a complete one-stop source for undergraduate/graduate pharmacists, pharmaceutical science students, and for those in the pharmaceutical industry. The Fourth Edition will completely update the previous edition, and will also include additional coverage on the newer approaches such as oligonucleotides, siRNA, gene therapy and nanotech.

The development of innovative drugs is becoming more difficult while relying on empirical approaches. This inspired all major pharmaceutical companies to pursue alternative model-based paradigms. The key question is: How to find innovative compounds and, subsequently, appropriate dosage regimens? Written from the industry perspective and based on many years of experience, this book offers: - Concepts for creation of drug-disease models, introduced and supplemented with extensive MATLAB programs - Guidance for exploration and modification of these programs to enhance the understanding of key principles - Usage of differential equations to pharmacokinetic, pharmacodynamic and (patho-) physiologic problems thereby acknowledging their dynamic nature - A range of topics from single exponential decay to adaptive dosing, from single subject exploration to clinical trial simulation, and from empirical to mechanistic disease modeling. Students with an undergraduate mathematical background or equivalent education, interest in life sciences and skills in a high-level programming language such as MATLAB, are encouraged to engage in model-based pharmaceutical research and development.

Biopharmaceutical medicines, the newest class of therapeutics, are quite heterogeneous and include a range of molecules such as proteins, peptides, vaccines and nucleic acids, with use in virtually all therapeutic fields (e.g. cancer and infectious diseases, vaccination, metabolic dysfunctions) and diagnostics. This edited book gives a concise and up-to-date overview of the biological features justifying the use of different human mucosa as delivery routes for biopharmaceuticals, the technological strategies that have been followed so far regarding the optimization of mucosal potentialities as well as the challenges that arise with the advent of new biopharmaceutical drugs and alternative means of administration. Following a brief introduction, the first section addresses general aspects of the biology of mucosal tissues and their unique aspects toward beneficial or deleterious interaction with biopharmaceuticals and their delivery systems. The second part reviews the different delivery strategies that have recently been investigated for different mucosal sites. The third section describes the development and clinical applications of drug delivery systems and products enclosing biopharmaceuticals for mucosal delivery, with a focus on the most successful case studies of recent years. The last section briefly centers on relevant aspects of the regulatory, toxicological and market issues of mucosal delivery of biopharmaceuticals. Scientists and researchers in the fields of drug delivery, material science, biomedical science and bioengineering as well as professionals, regulators and policy makers in the pharmaceutical, biotechnology and healthcare industries will find in this book an important compendium of fundamental concepts and practical tools for their daily research and activities.

The author has summarized a decade of teaching combinatorial chemistry into this timely brief. The solid phase synthesis of unnatural heterocyclic alpha-amino acids is illustrated by practical examples starting from the ABCs of peptide synthesis explored in chapter one. Chapter two is concerned with the solid phase synthesis which is shown on various techniques - BillBoard, tea-bag, and Lantern devices, and demonstrated on heterocyclic examples and protocols. In the third chapter the tools for accelerating chemical synthesis - solid phase and liquid phase - are reviewed. Here the techniques of parallel refluxing (including microwave and flow technique) and parallel separation (filtration, centrifugation, evaporation, and chromatography) are described. In the chapters 4 and 5 the author goes on to describe how the liquid phase synthesis of heterocycles (reductive amination and Ugi reaction of heterocycles) is illustrated with the use of semi-automated protocols. Finally, the design of combinatorial libraries of heterocycles is reviewed including the original author's findings.

The Medical Review Officer's Guide to Drug Testing makes it easy to understand current federal guidelines and select the best approaches for your needs. Tables, checklists, and record-keeping forms help you standardize your drug testing operations. This reference also reviews federal drug testing regulations, describes drug testing procedures and addresses risk management strategies.

First introduced to biomedical research in 1980, the term biomarker has taken on a life of its own in recent years and has come to mean a number of things. In biomedical science, biomarker has evolved to most commonly mean a characteristic that can be used either as a diagnostic or a prognostic, but most significantly as a screening indicator for pathologies that tend to be somewhat silent prior to overt clinical display. Applying scientific rigor, as well as a disciplined approach to nomenclature, Roger Lundblad's Development and Application of Biomarkers rationalizes the current enthusiasm for biomarkers with the use of well-established clinical laboratory analytes in clinical medicine. Highly respected for his work as both a classical protein scientist and as a pioneer in proteomics, Dr. Lundblad catalogs various biomarkers recognized in clinical medicine and, where possible, matches the expectations for advances in screening technologies with the realities of statistical analysis. More specifically, this important reference: Details an extensive list of biomarkers for various stages of a number of cancer types including ovarian, pancreatic, prostate, and breast cancer Looks at how proteomics is used for the discovery and validation of biomarkers Explores the use of microarray technology, ultra-high performance liquid chromatography, and computational bioinformatic approaches for the discovery and use of biomarkers Examines the use of cells and cell fragments as more complex biomarkers Organizes a host of significant biomarkers and essential research by type and use in a series of readily accessible tables Throughout this volume, Dr. Lundblad encourages consideration of biomarkers more as a concept than as laboratory analytes, emphasizing the relation between the discovery of a biomarker and the biology underlying its production. Ultimately, it is a thorough understanding of that underlying biology that will lead to the development of assays that are robust and reproducible, as well as clinically significant.