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 II contains chapters contributed by leading researchers in the field of systems and synthetic biology that concern modeling physiological processes and bottom-up constructions of scalable biological systems. The modeling problems include characterisation and synthesis of memory, understanding how homoeostasis is maintained in the face of shocks and relatively gradual perturbations, understanding the functioning and robustness of biological clocks such as those at the core of circadian rhythms, and understanding how the cell cycles can be regulated, among others. Some of the bottom-up construction problems investigated in Volume II are as follows: How should biomacromolecules, platforms, and scalable architectures be chosen and synthesised in order to build programmable de novo biological systems? What are the types of constrained optimisation problems encountered in this process and how can these be solved efficiently? 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.

Volume 47 of "Progress in Drug Research" contains eight reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with inotropic steroids, with chemokines and their involvement in a wide range of inflam matory diseases, with the subclassification and nomenclature of ul- and Uz-adrenoceptors, with Chinese traditional medicine, with drug targets in the molecular pathogenesis of asthma, with cytokines and their therapeutic application in immunosuppression and immunostimulation, with alter native medicine and with the potential use of calcium blockers in psy chiatry. These reviews and the quotations of original articles provide the reader with valuable information on several new developments in the world-wide search for new and better medicines. In 1959, when the Editor started this series of monographs, it was his intention to help disseminate informa tion on the vast and fast growing domain of drug research. Already at that time,it was not possible to follow the major individual publications in this field, and the reader was thereby provided with a tool to keep abreast of the latest developments and trends. This goal remained unchanged over the last 37 years, and I believe that the reviews in PDR are useful to the non-specialist who can obtain an overview of a particular field of drug research in a relatively short time.

In the early eighties when the H3 receptor was identified, many thought that an H3 ligand, an agonist or an antagonist, would become available as a therapeutic agent. This has not occurred. The reason for this could be the fact that many investigators consider histamine mainly, if not only, as a mediator present in for example mast cells being released during allergic events. However, it has become apparent that histamine is an important neurotransmitter. Its role in the nervous system, especially in the central part of it, is rather extensive.

The H3 receptor is mainly found as a presynaptic one, both on histaminergic neurons (the auto-type) and on other neuronal systems (the hetero-type). Both the H3 agonist and the H3 antagonist cause important pharmacological effects. Several ligands have become available now, including radiolabelled analogues.

In this book, the current state of affairs with regards to the medicinal chemistry and pharmacology of the H3 receptor and the several ligands available are presented by a number of experts in the field. The book presents an extended review of what has happened since the first H3 paper appeared. The editors hope that publication of this work will lead to an increase in interest of both academia and industry for the H3 receptor, especially as a target for drug development.

Long acting injections and implants improve therapy, enhance patient compliance, improve dosing convenience, and are the most appropriate formulation choice for drugs that undergo extensive first pass metabolism or that exhibit poor oral bioavailability. An intriguing variety of technologies have been developed to provide long acting injections and implants. Many considerations need to go into the design of these systems in order to translate a concept from the lab bench to actual therapy for a patient. This book surveys and summarizes the field. Topics covered in Long Acting Injections and Implants include the historical development of the field, drugs, diseases and clinical applications for long acting injections and implants, anatomy and physiology for these systems, specific injectable technologies (including lipophilic solutions, aqueous suspensions, microspheres, liposomes, in situ forming depots and self-assembling lipid formulations), specific implantable technologies (including osmotic implants, drug eluting stents and microfabricated systems), peptide, protein and vaccine delivery, sterilization, drug release testing and regulatory aspects of long acting injections and implants. This volume provides essential information for experienced development professionals but was also written to be useful for scientists just beginning work in the field and for others who need an understanding of long acting injections and implants. This book will also be ideal as a graduate textbook.

Significant progress has been made in the study of three-dimensional quantitative structure-activity relationships (3D QSAR) since the first publication by Richard Cramer in 1988 and the first volume in the series, 3D QSAR in Drug Design. Theory, Methods and Applications, published in 1993. The aim of that early book was to contribute to the understanding and the further application of CoMFA and related approaches and to facilitate the appropriate use of these methods. Since then, hundreds of papers have appeared using the quickly developing techniques of both 3D QSAR and computational sciences to study a broad variety of biological problems. Again the editor(s) felt that the time had come to solicit reviews on published and new viewpoints to document the state of the art of 3D QSAR in its broadest definition and to provide visions of where new techniques will emerge or new appli- tions may be found. The intention is not only to highlight new ideas but also to show the shortcomings, inaccuracies, and abuses of the methods. We hope this book will enable others to separate trivial from visionary approaches and me-too methodology from in- vative techniques. These concerns guided our choice of contributors. To our delight, our call for papers elicited a great many manuscripts.

Following the success of the first edition, this pioneering study of pharmaceuticals in the environment has been updated and greatly extended. It includes the status of research on pharmaceuticals in soil, with attention to terrestrial and aquatic environments as well as new substance categories such as tetracylines and chinolones and the latest results concerning contamination of the environment and risk reduction.

This volume of Pharmacochemistry Library comprises the text of invited lectures presented at the 11th Noordwijkerhout-Camerino Symposium "Trends in Drug Research," held in Noordwijkerhout, The Netherlands, from 11-15 May 1997.

In the programme attention has been given to the generation of new biological target systems and the generation of new lead molecules, with presentations on e.g. combinatorial chemistry, compound libraries, database search, high throughput screening and molecular biology.

Other topics discussed were the perspectives for new medicines for the gastro-intestinal tract, the major developments in the search for effective anti-HIV drugs and new aspects in synthetic approaches. In a special session three topics which currently draw much attention were discussed: How to deal with the major problem of resistance against antimirobial agents? Can the apoptosis mechanism be used as a drug target? Is the newly observed phenomenon of inverse agonism a general principle and has it consequences for drug development (and use?)

Vaso-occlusive disorders including unstable angina, myocardial infarction, transient ischemic attacks, stroke and peripheral artery disease remain the major sources of morbidity and mortality in western civilization. Platelet activation and resulting platelet aggregation play a major role in the pathogenesis of these thromboembolic diseases. Recognition of the contribution of platelets to the pathophysiology of cardiovascular disease has provided impetus for the continued search for new antiplatelet agents. Hence, over the past two decades many strategies have been evaluated in the search for efficacious mechanisms to reduce platelet function. The medical need for more efficacious antithrombotic drugs and the growing understanding of the role of platelets in vascular injury have catalyzed the extensive evaluation of novel approaches to control platelet function. Along these lines, the volume therefore provides an in-depth assessment of ongoing clinical trials, new and clinically established agents, and other developments in this rapidly developing field.

Neuropeptide Y (NPY) is a ubiquitous and important messenger in the nervous system, with a wide range of physiological roles. It is involved in the body energy balance and is one of the most potent stimuli of food intake known. NPY also acts to regulate central and peripheral autonomic functions.
This book, written by academic and industrial experts in the field, links the most recent basic experimental knowledge about NPY and its receptors with areas of clinical importance.
This book will be of interest to those working in all areas of research affected by NPY, such as food intake and energy homeostasis, cardiovascular regulation and G-protein-coupled receptors, as well as those interested in the development of drugs as NPY targets.
Key Features
* The hypothalamic role of NPY and its relationship with eating disorders and diabetes
* The sympathetic nervous system role of NPY and its involvement in cardiovascular disorders
* Characterization of NPY receptor types and their brain distribution, molecular biology and pharmacology
* Development of peptide and non-peptide receptor antagonists

Genetic Algorithms in Molecular Modeling is the first book available on the use of genetic algorithms in molecular design. This volume marks the beginning of an ew series of books, Principles in Qsar and Drug Design, which will be an indispensible reference for students and professionals involved in medicinal chemistry, pharmacology, (eco)toxicology, and agrochemistry. Each comprehensive chapter is written by a distinguished researcher in the field.
Through its up to the minute content, extensive bibliography, and essential information on software availability, this book leads the reader from the theoretical aspects to the practical applications. It enables the uninitiated reader to apply genetic algorithms for modeling the biological activities and properties of chemicals, and provides the trained scientist with the most up to date information on the topic.
. Extremely topical and timely
. Sets the foundations for the development of
computer-aided tools for solving numerous
problems in QSAR and drug design
. Written to be accessible without prior direct
experience in genetic algorithms

"In Vitro" Methods in Pharmaceutical Research provides a comprehensive guide to laboratory techniques for evaluating "in vitro" organ toxicity using cellular models. Step-by-step practical tips on how to perform and interpret assays for drug metabolism and toxicity assessment are provided, along with a comparison of different techniques available. It is a welcome addition to the literature at a time when interest is growing in cellular "in vitro" models for toxicology and pharmacology studies.
Key Features
* Meets the continuing demand for information in this field
* Compares "In Vitro" techniques with other methods
* Describes cell-culture methods used to investigate toxicity in cells derived from different organs
* Includes contributions by leading experts in the field

The purpose of this book is to give a concise introduction to development and analysis of pharmaceutical biologics for those in the pharmaceutical industry who are switching focus from small molecules to biologics processing, analysis, and delivery. In order to maintain a limited focus, Introduction to Biologic and Biosimilar Product Development and Analysis, will deal only with peptides, proteins and monoclonal antibodies.

The rise of bio- and nano-technology in the last decades has led to the emergence of a new and unique type of medicine known as non-biological complex drugs (NBCDs). This book illustrates the challenges associated with NBCD development, as well as the complexity of assessing the effects of manufacturing changes on innovator and follow-on batches of NBCDs. It also touches upon proven marketing authorization requirements for biosimilars that could be effective in evaluating follow-on NBCDs, including a demonstration of control over the manufacturing process and a need for detailed physico-chemical characterization and (pre)clinical tests. This book is meant to be used for years to come as a standard reference work for the development of NBCDs. Moreover, this book aims to stimulate discussions and further our thinking to ensure that decisions regarding the approval of complex drugs are made with relevant scientific data on the table.

The seventh volume of Advances in Pharmaceutical Sciences heralds a welcome continuation of this well-respected series. Acknowledged experts provide comprehensive statements of current research and development in selected fields of pharmaceutical technology. This book will be of great value to those working in academia and the pharmaceutical industry.

Through this monograph, the pharmaceutical chemist gets familiar with the possibilities electroanalytical methods offer for validated analyses of drug compounds and pharmaceuticals. The presentation focuses on the techniques most frequently used in practical applications, particularly voltammetry and polarography. The authors present the information in such a way that the reader can judge whether the application of such techniques offers advantages for solving a particular analytical problem. Basics of individual electroanalytical techniques are outlined using as simple language as possible, with a minimum of mathematical apparatus. For each electroanalytical technique, the physical and chemical processes as well as the instrumentation are described. The authors also cover procedures for the identification of electroactive groups and the chemical and electrochemical processes involved. Understanding the principles of such processes is essential for finding optimum analytical conditions in the most reliable way. Added to this is the validation of such analytical procedures. A particularly valuable feature of this book are extensive tables listing numerous validated examples of practical applications. Various Indices according to the drug type, the electroactive group and the type of method as well as a subject and author index are also provided for easy reference.

Poucher's Perfumes Cosmetics and Soaps has been in print since 1923 and is the classic reference work in the field of cosmetics. Now in a fully updated 10th edition, this new volume provides a firm basic knowledge in the science of cosmetics (including toiletries) as well as incorporating the latest trends in scientific applications and legislation which have occurred since the 9th edition. This edition will not only be an excellent reference book for students entering the industry but also for those in specialized research companies, universities and other associated institutions who will be able to gain an overall picture of the modern cosmetic science and industry. The book has been logically ordered into four distinct parts. The historical overview of Part 1 contains an essay demonstrating William Arthur Poucher's influence on the 20th Century cosmetics industry as well as a chapter detailing the long history of cosmetics. Part 2 is a comprehensive listing of the properties and uses of common cosmetic types, ranging from Antiperspirants through to Sunscreen preparations. There are an increased number of raw materials in use today and their chemical, physical and safety benefits are carefully discussed along with formulation examples. The many additions since the last edition demonstrate the dramatic recent expansion in the industry and how changes in legal regulations affecting the development, production and marketing of old, established and new products are operative almost worldwide. Information on specialist products for babies and others is included within individual chapters. The chapters in Part 3 support and outline the current guidelines regarding the assessment and controlof safety and stability. This information is presented chemically, physically and microbiologically. Part 3 chapters also detail requirements for the consumer acceptability of both existing and new products. Those legal regulations now in force in the EU, the USA and Japan are carefully described in a separate chapter and the remaining chapters have been extensively updated to explain the technical and practical operations needed to comply with regulations when marketing. This information will be invaluable to European Union and North American companies when preparing legally required product information dossiers. The final chapters in Part 4 contain useful information on the psychology of perfumery as well as detailing methods for the conduct of assessment trials of new products. As ingredient labelling is now an almost universal legal requirement the International Nomenclature of Cosmetics Ingredients (INCI) for raw materials has been used wherever practicable. The advertised volume is the 10th edition of what was previously known as volume 3 of Poucher's Cosmetics and Soaps. Due to changes in the industry there are no plans to bring out new editions of volume 1 and 2.

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.

High-throughput screening and combinatorial chemistry are two of the most potent weapons ever to have been used in the discovery of new drugs. At a stroke, it seems to be possible to synthesise more molecules in a month than have previously been made in the whole of the distinguished history of organic chemistry, Furthermore, all the molecules can be screened in the same short period. However, like any weapons of immense power, these techniques must be used with care, to achieve maximum impact. The costs of implementing and running high-throughput screening and combinatorial chemistry are high, as large dedicated facilities must be built and staffed. In addition, the sheer number of chemical leads generated may overwhelm the lead optimisation teams in a hail of friendly fire. Mother nature has not entirely surrendered, as the number of building blocks that could be used to build libraries would require more atoms than there are in the universe. In addition, the progress made by the Human Genome Project has uncovered many proteins with different functions but related binding sites, creating issues of selectivity. Advances in the new field of pharmacogenomics will produce more of these challenges. There is a real need to make hi- throughput screening and combinatorial chemistry into 'smart' weapons, so that their power is not dissipated. That is the challenge for modellers, computational chemists, cheminformaticians and IT experts. In this book, we have broken down this grand challenge into key tasks.

Since penicillin and salvarsan were discovered, a number of new drugs to combat infectious diseases have been developed, but at the same time, the number of multi-resistant microorganism strains is increasing. Thus, the design of new and effective antibacterial, antiviral and antifungal agents will be a major challenge in the next years. This book reviews the current state-of-the-art in antimicrobial research and discusses new strategies for the design and discovery of novel therapies. Topics covered include the use of genetic engineering, genome mining, manipulation of gene clusters, X-ray and neutron scattering as well as the antimicrobial effects of essential oils, antimicrobial agents of plant origin, beta-lactam antibiotics, antimicrobial peptides, and cell-wall-affecting antifungal antibiotics.

It is evident that biochemical control is not strictly hierarchical and that intermediary metabolism can contribute to control of regulatory pathways. Metabolic studies are therefore increasingly important in gene function analyses, and an increased interest in metabolites as biomarkers for disease progression or response to therapeutic intervention is also evident in the pharmaceutical industry. This book offers guidelines to currently available technology and bioinformatics and database strategies now being developed. Evidence is presented that metabolic profiling is a valuable addition to genomics and proteomics strategies devoted to drug discovery and development, and that metabolic profiling offers numerous advantages.

This book is the first to summarize new technologies for engineered cell manipulation. The contents focus on control of cellular functions by nanomaterials and control of three-dimensional cell-cell interactions. Control of cellular functions is important for cell differentiation, maturation, and activation, which generally are controlled by the addition of soluble cytokines or growth factors into cell culture dishes. Target antigen molecules can be efficiently delivered to the cytosol of the dendritic cells using the nanoparticle technique described here, and cellular functions such as dendritic cell maturation can be controlled easily and with precision. This book describes basic preparation of the nanoparticles, activation control of dendritic cells, immune function control, and in vivo application for various vaccination systems. The second type of control,that of cell-cell interaction, is important for tissue engineering in order to develop three-dimensional cellular constructs. To achieve in vitro engineering of three-dimensional human tissue constructs, cell-cell interaction must be controlled in three dimensions, but typical biological cell manipulation technique cannot accomplish this task. An engineered cell manipulation technique is necessary. In this book the authors describe the fabrication of nanofilms onto cell surfaces, development of three-dimensional cellular multilayers, and various applications of the cellular multilayers as three-dimensional human models. This important work will be highly informative for researchers and students in the fields of materials science, polymer science, biomaterials, medicinal science, nanotechnology, biotechnology, and biology.

The plant' is often the most neglected part of plant-based medicine. Throughout time, humans have searched, collected, and effectively used plants for healing. Currently, the medicinal plant-based business is flourishing at a dramatic pace and at the expense of an already declining population of plant species, many of which are on the verge of extinction. In spite of this history and popularity, the mystery of what transforms a plant into a medicinal plant persists, and there are chronic problems with ensuring the safety and efficacy of medicinal plant products. Therefore, there is a real need for a full characterization of medicinal plant species and for the development and application of novel technologies for the production of plant-based medicines. This book highlights some of the recent advances and new approaches to the development of technologies for plant-based medicines and is intended to stimulate new discussions among researchers, regulatory authorities, and pharmaceutical organizations, leading to significant advancements in the field.

The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.

An in-depth exploration of the applications of plant bioactive metabolites in drug research and development

Highlighting the complexity and applications of plant bioactive metabolites in organic and medicinal chemistry, "Plant Bioactives and Drug Discovery: Principles, Practice, and Perspectives" provides an in-depth overview of the ways in which plants can inform drug research and development. An edited volume featuring multidisciplinary international contributions from acclaimed scientists researching bioactive natural products, the book provides an incisive overview of one of the most important topics in pharmaceutical studies today.

With coverage of strategic methods of natural compound isolation, structural manipulation, natural products in clinical trials, quality control, and more, and featuring case studies on medicinal plants, the book serves as a definitive guide to the field of plant biodiversity as it relates to medicine. In addition, chapters on using natural products as drugs that target specific disease areas, including neurological disorders, inflammation, infectious diseases, and cancer, illustrate the myriad possibilities for therapeutic applications.

Wide ranging and comprehensive, "Plant Bioactives and Drug Discovery" also includes important information on marketing, regulations, intellectual property rights, and academic-industry collaboration as they relate to plant-based drug research, making it an essential resource for advanced students and academic and industry professionals working in biochemical, pharmaceutical, and related fields.

Infectious diseases caused by viruses, parasites, bacteria, and fungi are the number one cause of death worldwide. Although new technologies have improved diagnosis of infectious diseases, the efficacy of all known current anti-infective agents is threatened by the spread of drug-resistant forms of the pathogens. Hence, there remains an urgent need to develop anti-infective agents that target drug-resistant pathogens. In Silico Models for Drug Discovery presents a comprehensive look at the role in silico models play in understanding infectious diseases and in developing novel therapeutics to treat them. Written by leading experts in the field, chapters cover topics such as techniques to derive novel antimicrobial targets, methods of interpreting polypharmacology-based drug target networks, and molecular dynamics techniques used to compute binding energies of drugs to their target proteins, to name a few. Written in the successful Methods in Molecular Biology (TM) series or in review article 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, In Silico Models for Drug Discovery seeks to serve both professionals and novices involved in the study and treatment of infectious diseases.