The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimers disease, Parkinson s disease, Huntington s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society. "

This volume presents key topics of current interest with regard to several pathophysiological conditions including (a) the basic and clinical aspects of bradykinin receptor antagonists, (b) the kallikrein-kinin pathways in hypertension and diabetes, (c) tissue kallikrein-kinin therapy for hypertension and organ damage, (d) the renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension, (e) the kallikrein-kinin system in diabetes retinopathy and (f) genetic manipulation and genetic variation of the kallikrein-kinin system and their impacts on cardiovascular and renal disease. Written by internationally reputed scientists, the book provides an essential overview of the latest developments in the field of kinin research, making it a valuable asset for endocrinologists, nephrologists, cardiologists, pharmacologists, physiologists, ophthalmologists and rheumatologists. Furthermore, it is also intended for postgraduate students in the fields of medicine, pharmacy, physiology and pharmacology and those working at research organizations.

1. Gene Therapy.- Asthma.- 2. Genetics of Asthma.- 3. Transcription Factors and Inflammatory Lung Disease.- 4. Regulation of the Cytokine Gene Cluster on Chromosome 5q.- 5. Cytokine Expression in Asthma.- 6. ?-Adrenoceptors.- 7. Regulation of Eosinophil Migration.- 8. Proteinase Allergens of House Dust Mites: Molecular Biology, Biochemistry and Possible Functional Significance of Their Enzyme Activity.- Cancer.- 9. Gene Expression in Lung Cancer.- 10. Gene Therapy for Cancer: Prospects for the Treatment of Lung Tumours.

The book will provide an exhaustive and clear explanation of how Statistics, Mathematics and Informatics have been used in cancer research, and seeks to help cancer researchers in achieving their objectives. To do so, state-of-the-art Biostatistics, Biomathematics and Bioinformatics methods will be described and discussed in detail through illustrative and capital examples taken from cancer research work already published. The book will provide a guide for cancer researchers in using Statistics, Mathematics and Informatics, clarifying the contribution of these logical sciences to the study of cancer, thoroughly explaining their procedures and methods, and providing criteria to their appropriate use.

Fluorine chemistry is an expanding area of research that is attracting international interest, due to the impact of fluorine in drug discovery and in clinical and molecular imaging (e.g. PET, MRI). Many researchers and academics are entering this area of research, while scientists in industrial and clinical environments are also indirectly exposed to fluorine chemistry through the use of fluorinated compounds for imaging.This book provides an overview of the impact that fluorine has made in the life sciences. In the first section, the emphasis is on how fluorine substitution of amino acids, peptides, nucleobases and carbohydrates can provide invaluable information at a molecular level. The following chapters provide answers to the key questions posed on the importance of fluorine in drug discovery and clinical applications. For examples, the reader will discover how fluorine has found its place as a key element improving drug efficacy, with reference to some of the best-selling drugs on the market. Finally, a thorough review on the design, synthesis and use of 18F-radiotracers for positron emission tomography is provided, and this is complemented with a discussion on how 19F NMR has advanced molecular and clinical imaging.

"Omics for Personalized Medicine" will give to its prospective readers the insight of both the current developments and the future potential of personalized medicine. The book brings into light how the pharmacogenomics and omics technologies are bringing a revolution in transforming the medicine and the health care sector for the better. Students of biomedical research and medicine along with medical professionals will benefit tremendously from the book by gaining from the diverse fields of knowledge of new age personalized medicine presented in the highly detailed chapters of the book. The book chapters are divided into two sections for convenient reading with the first section covering the general aspects of pharmaocogenomic technology that includes latest research and development in omics technologies. The first section also highlights the role of omics in modern clinical trials and even discusses the ethical consideration in pharmocogenomics. The second section is focusing on the development of personalized medicine in several areas of human health. The topics covered range from metabolic and neurological disorders to non-communicable as well as infectious diseases, and even explores the role of pharmacogenomics in cell therapy and transplantation technology. Thirty-four chapters of the book cover several aspects of pharmacogenomics and personalized medicine and have taken into consideration the varied interest of the readers from different fields of biomedical research and medicine. Advent of pharmacogenomics is the future of modern medicine, which has resulted from culmination of decades of research and now is showing the way forward. The book is an honest endeavour of researchers from all over the world to disseminate the latest knowledge and knowhow in personalized medicine to the community health researchers in particular and the educated public in general.

This volume aims to connect current ideas and concepts about GI disorders with the search for novel therapeutics. Towards this goal, authors provide a timely state-of-the-art overview of the GI tract in health and disease, current treatment approaches and ongoing developments in drug discovery, and their potential for the better treatment of patients with GI disorders.

This special issue of the Handbook of Experimental Pharmacology on Heart Failure covers the entire spectrum of the field, from the current understanding and definitions of heart failure, to epidemiology and the importance of co-morbidities, clinical trial design and biomarkers, as well as imaging technologies. The main focus of this book is to review current and emerging heart failure therapies and potential targets for treatment.

Here, front-line researchers in the booming field of nanobiotechnology describe the most promising approaches for bioinspired drug delivery, encompassing small molecule delivery, delivery of therapeutic proteins and gene delivery. The carriers surveyed include polymeric, proteinaceous and lipid systems on the nanoscale, with a focus on their adaptability for different cargoes and target tissues.
Thanks to the broad coverage of carriers as well as cargoes discussed, every researcher in the field will find valuable information here.

Although antiviral drugs have been successfully developed for some viral diseases, there remains a clear, unmet medical need to develop novel antiviral agents for the control and management of many viruses that currently have no or limited treatment options as well as a need to overcome the limitations associated with the existing antiviral drugs, such as adverse effects and emergence of drug-resistant mutations. The second edition of Antiviral Methods and Protocols features: All chapters are new and written by experts in the field, reflecting the major recent technical advances in antiviral research and discovery. This edition focuses on many important human viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis viruses (hepatitis B and C viruses), herpes viruses, human respiratory syncytial virus (RSV), and influenza virus, while also featuring some important emerging viruses, such as dengue virus, West Nile virus, and chikungunya virus. As a volume in 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. Comprehensive and cutting-edge, Antiviral Methods and Protocols, Second Edition will serve as an excellent laboratory reference for pharmaceutical and academic biologists, medicinal chemists, and pharmacologists as well as for virologists in the field of antiviral research and drug discovery.

The objective of this volume is to give an overview of the present state of the art of pediatric clinical pharmacology including developmental physiology, pediatric-specific pathology, special tools and methods for development of drugs for children (assessment of efficacy, toxicity, long-term safety etc.) as well as regulatory and ethical knowledge and skills. In the future, structural and educational changes have to lead back to a closer cooperation and interaction of pediatrics with (clinical) pharmacology and pharmacy.

This book sheds new light on the development and use of quantitative models to describe the process of skin permeation. It critically reviews the development of quantitative predictive models of skin absorption and discusses key recommendations for model development. Topics presented include an introduction to skin physiology; the underlying theories of skin absorption; the physical laboratory-based processes used to generate skin absorption data, which is in turn used to construct mathematical models describing the skin permeation process; algorithms of skin permeability including quantitative structure-activity (or permeability) relationships (QSARs or QSPRs); relationships between permeability and molecular properties; the development of formulation-focused approaches to models of skin permeability prediction; the use of artificial membranes, e.g. polydimethylsiloxane as alternatives to mammalian skin; and lastly, the use of novel Machine Learning methods in developing the next generation of predictive skin permeability models. The book will be of interest to all researchers in academia and industry working in pharmaceutical discovery and development, as well as readers from the field of occupational exposure and risk assessment, especially those whose work involves agrochemicals, bulk chemicals and cosmetics.

Vitamins and Hormones is the longest-running serial published by Academic Press. The Editorial Board reflects expertise in the fields of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Every volume contains comprehensive reviews by leading contributors.

Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. This comprehensive volume brings together the current knowledge from different relevant areas, including molecular mechanisms and translational aspects of drug resistance in AIs. Topics covered include research, experimental , and clinical data specifically focused on AI resistance in breast cancer. The volume will include three sections. The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure and function of aromatase protein. The second section provides the detailed mechanisms of resistance to AIs, while the third section explores prediction of resistance and potential strategies to overcome resistance. Breast cancer is the most common female cancer and AIs significantly improve treatments outcomes compatibly to previously used endocrine treatments. However 10-15% of post-operative patients develop a relapse during adjuvant treatment with AIs; about 25-50% of the patients do not respond to AIs in neo-adjuvant or metastatic setting, and the majority of metastatic patients who initially respond develop resistance within 3 years. There is an important need to understand these mechanisms of resistance in order to develop methods of preventing or overcoming the resistance to AIs, which will ensure a more successful outcome in treating breast cancer.

Due to the failing "one-drug-fits-all" model, it has become increasingly necessary to develop personalized medicine that treats whole systems and brings the right drug to the right patient with the right dosages. In Systems Biology in Drug Discovery and Development: Methods and Protocols, leading experts provide a practical, state-of-the-art, and holistic view of the translation of systems biology into better drug discovery and personalized medical practice. While the first part of the book describes cutting-edge technologies and methods in the field, the second part illustrates how the technologies can be applied in science for disease understanding and therapeutic discovery. As a volume in the highly successful Methods in Molecular Biology (TM) series, this collection provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and up-to-date, Systems Biology in Drug Discovery and Development: Methods and Protocols covers topics from fundamental concepts to advanced technologies in order to best serve biomedical students and professionals at all levels who are interested in vital integrative studies in molecular biology, genetics, bioinformatics, bioengineering, biochemistry, physiology, pathology, microbiology, immunology, pharmacology, toxicology, drug discovery, and clinical medicine.

This second edition book explores breakthrough technologies in the field of drug target identification and validation. The volume emphasizes particularly revolutionary technologies, such as CRISPR-related screening, "big data," and in silico approaches, as well as in vivo applications of CRISPR and best uses of animal models in drug development. 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. Fully updated and authoritative, Target Identification and Validation in Drug Discovery: Methods and Protocols, Second Edition is an ideal guide for molecular and cellular biologists, pharmacologists, pathologists, bioinformaticians, clinical researchers, or investigators, as well as experts in other fields that need a quick overview of these state-of-the-art technologies.

Osteoimmunology pertains to the study of the relationship between the bones, particularly the bone marrow, and the immune system. This monograph pursues the best available evidence, by means of research synthesis, for the characterization of the physiological relevance and pathological implications of the inter-connectedness between the skeletal and the immune system. Research will be discussed that highlights the associated role of the circulatory, nervous and endocrine systems, as well as proteomic and genomic pathways and signatures. Emphasis is given that domain of medicine that relates to the oral cavity, its diseases and their systemic sequelae. This monograph arises from observations that have suggested that the skeletal system and the immune system are intimately intertwined. Chronic inflammatory reactions subsequent to an excessive immune reaction can damage the bones, as in rheumatoid arthritis (RA), osteoporosis, patients seropositive for the human immunodeficiency virus (HIV)-1 and with signs and symptoms of the acquired immune deficiency syndrome (AIDS), and bone cancer. Bones - in particular the bone marrow - are one of the primary locations in which cells of the immune system mature. In brief, this monograph begins to answer a range of questions, such as, what is osteoimmunology all about?, does the immune system and its components affect bone development?, how do stress hormones impact upon the pathophysiology of bone-immune interactions?, can the scientific process of research synthesis, obtain the best available evidence for treatment of diseases involving the bone-immune entity (i.e., osteo immunopathologies) means of evidence-based clinical decision-making directed at the treatment of osteoimmune pathologies?

This volume presents 30 state-of-the-art protocols and reviews to set up and apply primary hepatocyte cultures for research and screening purposes. The first part of the book focuses on the use of these particular liver-based in vitro models to study the different aspects of the hepatocyte life cycle, including cell growth, differentiation and cell death. The second part of the book is targeted towards the demonstration of the applicability of primary hepatocyte cultures, or liver-based in vitro models derived thereof, for functionality and toxicity testing. 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 and readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Protocols In In-Vitro Hepatocyte Research is intended for basic and applied researchers in the area of pharmacology and toxicology, both in academic and industrial settings.

G Protein-Coupled Receptor Genetics: Research and Methods in the Post-Genomic Era features practical techniques inspired by the fast moving GPCR field. From powerful bioinformatic tools tracing the evolution of GPCRs, to methods for the cellular transfection of engineered viruses containing GPCRs, to optogenetic techniques that produce light-activated GPCRs in live mice, what was once science fiction is now science fact. This detailed volume includes sections covering genetic mechanisms, a genetic toolbox for GPCR discovery, as well as genetic aspects of G protein-coupled receptors in health and medicine. Written for the Methods in Pharmacology and Toxicology series, this book contains the kind of key implementation advice that encourages successful results in the lab. Authoritative and easy to use, G Protein-Coupled Receptor Genetics: Research and Methods in the Post-Genomic Era serves as an ideal guide for researchers aiming to continue our progress in this dynamic and exciting area of study.