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.

This book presents original results on the leading edge of cancer research. Chapter One reviews the most recent advances in the management, analyses the best possible treatment in each scenario, and discusses the future research direction on brain metastases from non-small cell lung cancer. Chapter Two discusses the positive effects of microscopic complete resection on controlling the local recurrence of a single brain metastasis. Chapter Three encapsulates the trends of the computer-aided diagnosis (CAD) development for the estimation of tumor malignancy. Chapter Four examines dendritic cells cross talk with cytomegalovirus pp65-specific cytotoxic T cells, V 9 T cells, and invariant NKT cells in patients with glioblastoma multiforme. Chapter Five addresses CD8+ T cell activation and regulation in the skin, paying special attention to what it is known about CD8+ T cell activity and its link with SCC development. Chapter Six discusses knowledge of the molecular basis of anti-cancer drug resistance and the mechanisms through which triterpenoids modulate ABC transporter-mediated multi drug resistance. Chapter Seven reviews cancer and heparan sulfate alterations. Chapter Eight focuses on Ganoderma lucidum targeting apoptosis. Chapter Nine examines the integrated model of cAMP-dependent DNA expression which reveals an inverse relationship between cancer and neurodegeneration. Chapter Ten studies the prognosis of male breast cancer.

This book provides readers with the latest developments in neuroscience research. Chapter One discusses the development of neurochemical characteristics of sensory neurons. Chapter Two reviews current knowledge regarding Mavridis' area (MA) and its role as a modern stereotactic microanatomic guide for nucleus accumbens (NA) deep brain stimulation (DBS). Chapter Three describes the molecular mechanisms in response to exposure of the central nervous system (CNS) cells to the Ca2+ ionophores to increase the levels of intracellular free Ca2+ and consequently oxidative stress, and it also describes the roles of activation of the Ca2+-dependent proteases and intracellular pathways leading to induction of programmed cell death. Chapter Four reviews clinical features, epidemiology, genetics, physiopathology, management and advanced research on Frontotemporal Dementia and Frontotemporal Lobar Degeneration (FTLD). Chapter Five explores different terpenes and their role in signaling pathway modulating the progression of Alzheimer Disease. Chapter Six discusses the capability of and limitations in PET imaging research on non-human primates for translation to humans for brain aging research as well as therapeutic drug development for neurodegenerative diseases. Chapter Seven studies the imaging markers and prognostic significance of intracerebral hemorrhages (ICH). Chapter Eight reviews clinical practices and surgical intervention for ICH.

Growth in the pharmaceutical market has slowed down - almost to a standstill. One reason is that governments and other payers are cutting costs in a faltering world economy. But a more fundamental problem is the failure of major companies to discover, develop and market new drugs. Major drugs losing patent protection or being withdrawn from the market are simply not being replaced by new therapies - the pharmaceutical market model is no longer functioning effectively and most pharmaceutical companies are failing to produce the innovation needed for success. This multi-authored new book looks at a vital strategy which can bring innovation to a market in need of new ideas and new products: Systems Biology (SB). Modeling is a significant task of systems biology. SB aims to develop and use efficient algorithms, data structures, visualization and communication tools to orchestrate the integration of large quantities of biological data with the goal of computer modeling. It involves the use of computer simulations of biological systems, such as the networks of metabolites comprise signal transduction pathways and gene regulatory networks to both analyze and visualize the complex connections of these cellular processes. SB involves a series of operational protocols used for performing research, namely a cycle composed of theoretical, analytic or computational modeling to propose specific testable hypotheses about a biological system, experimental validation, and then using the newly acquired quantitative description of cells or cell processes to refine the computational model or theory.

The book will discuss the molecular mechanisms of cancer diseases, stem cell proliferation and transformation into cancer cells beyond the physiological processes that occur in normal stem cell biology. Some of the key oncogenic events in cancer and their signaling pathways that regulate cell division cycle progression will be described considering prospects for using such knowledge in advanced cancer therapy. Each chapter shall provide an invaluable resource for information on the most current advances in the field, with discussion of controversial issues and areas of emerging importance

This well-illustrated textbook covers the full range of lung and pleural diseases from the pathologic standpoint. Both diseases of adults and pediatric lung diseases are presented. The book will serve as an excellent guide to the diagnosis of these diseases, but in addition it explains the disease mechanisms and etiology. Genetics and molecular biology are also discussed whenever necessary for a full understanding. The author is an internationally recognized expert who runs courses on lung and pleural pathology attended by participants from all over the world. In compiling this book, he has drawn on more than 30 years' experience in the field.

The purpose of this book is to introduce the importance of vitamins and its use in the treatment of schizophrenia, mood and movement disorders. This subject has been already known for many years. In the last years this issue has become "hot" again. To date there is new modern data based on controlled studies leading to a new attitude in consumption of these preparations. The present experience is related to higher doses in contrast to those which were used previously in addition to the scientific base data consisting of new knowledge about the mechanism of action and the influence on different dimensions. The chapters will include theoretical and scientific background as well as practical data based conclusions which might be useful for the clinician in everyday practice.

Respiration is an area of the medical study that undergoes fast developments. A better understanding of the neural and cellular mechanisms underlying respiratory disorders and lung function is essential for the evidence-based pharmacotherapy and for optimizing the patient care and prophylactic measures to improve the health and quality of life. This comprehensive book is a blend of basic and clinical research. The book is thought to promote the translation of science into clinical practice. The book presents an update on the areas of current research and clinical interest in the neurobiology of the respiratory system. Recent innovations in detection and management of respiratory diseases are described. The book will be a base of reference in the field of respiration for years to come and a source of future research ideas. This book is a required text for respiratory scientists, neuropathologists, and for clinicians searching for 'bench to bedside' treatments of lung diseases.

This book will provide latest insights in the functional potentials of ribonucleic acids in medine and the use of Spiegelmer and Spiegelzyme systems. It will also deal with a new type of delivery systems for cellular targeting.

This book provides the most updated information of how membrane lipids mediate protein signaling from studies carried out in animal and plant cells. Also, there are some chapters that go beyond and expand these studies of protein-lipid interactions at the structural level. The book begins with a literature review from investigations associated to sphingolipids, followed by studies that describe the role of phosphoinositides in signaling and closing with the function of other key lipids in signaling at the plasma membrane and intracellular organelles.

Two decades have passed since trinucleotide repeat expansion was first discovered in genes responsible for certain neurological diseases. Since then, new technologies have developed and innovative concepts have emerged, which may prove useful in devising therapeutic approaches to neurological diseases. Divided into six convenient sections, Trinucleotide Repeat Protocols, Second Edition covers a wide range of topics such as an overview of trinucleotide repeat diseases, synaptic plasticity, embryonic stem (ES) cell-related protocols with a focus on HD, RNA-related protocols, and analysis of epigenetic modification in fragile X syndrome. This edition focuses not only on direct analysis of trinucleotide repeat diseases but also on alternative approaches for the analysis of trinucleotide repeat diseases, with the hope that this will result in a better understanding of the mechanisms and future therapeutic prospects for treatment of these diseases. Written in the successful Methods in Molecular Biology (TM) 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, Trinucleotide Repeat Protocols, Second Edition seeks to serve researchers with its thorough methodologies on this expanding field.

Much has been written about the basic incompatibility of the dominant quantitative research model in psychotherapy and the qualitative preferences of the practitioner community providing psychotherapy. Researchers and clinicians are at odds over the most valuable type of knowledge needed: that emerging from quantitative, experimental research versus that from qualitative, case-based practice, respectively. Recently, a number of emerging research methods have attempted to bridge and integrate these two approaches. Case Studies within Psychotherapy Trials is one such effort and significantly furthers the synergy between them. The volume provides a comprehensive illustration of the "cases-within-trials" (CWT) model of research. Quantitative findings from four randomized clinical trials (RCT) are synthesized with qualitative and quantitative findings from systematic case studies of successful and unsuccessful clients representatively drawn from each RCT. The book opens with the history of dialectic and political controversy in psychotherapy research and recent initiatives to bridge the differing perspectives. The RCT and case study projects follow, each commented on by outside experts. In the final chapter the editors compare and contrast the separate projects and draw insightful, impactful conclusions. By bringing together quantitative, natural scientific perspectives on research and qualitative, interpretative understandings and strategies, the chapter authors demonstrate how practitioners can be meaningfully included in future psychotherapy research. This book will be of great interest to psychotherapy researchers and practitioners and those interested in research methods in the behavioral sciences more generally.

In this book we have taken a comprehensive look at the subject of familial and hereditary gastric tumors. In particular, the aim of this novel editorial work is to propose the correct management of hereditary diffuse gastric cancer patients, focusing in particular on E-cadherin germline mutations, clinical criteria definition, genetic screening and molecular mechanisms, pathology and microscopic features, surgical treatment and clinical approach for asymptomatic mutation carriers. We also describe other inherited predispositions involving gastric carcinoma.

Continuous regeneration of the cornea is necessary to maintain this tissue in the transparent state that is essential for vision. Therapy for repair of the damaged anterior cornea is currently addressed through the transplantation of donor corneas or the delivery of limbal epithelial stem cells (LESC) to the ocular surface using amniotic membrane (AM) as a supporting scaffold. Research on the bioengineering of corneal equivalents as replacement tissue is underway to develop viable corneal prosthetics. Corneal Regenerative Medicine: Methods and Protocols provides a concise overview of essential techniques in the field of corneal regenerative medicine, highlighting novel strategies to guide the management of key therapies within this area of medicine. Divided into four convenient sections, topics include the identification, characterisation and cultivation of LESC, as well as the investigation of biopolymers used as the basis for corneal substitutes. 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, Corneal Regenerative Medicine: Methods and Protocols covers the fundamental techniques useful for both the laboratory and clinical settings.

Stem cells are central to the development and homeostasis of metazoan tissues and play roles at multiple times within a diversity of organs during the lifetime of an animal. A key goal of regenerative medicine is the in vivo repair of organs damaged by disease or injury. In order to facilitate this goal we need to understand how stem cells are generated, what factors maintain them in their respective tissues and how their differentiation is regulated. In this volume, leading researchers discuss the nature of stem cells and pluripotency and how this state can be experimentally induced. Stem cell maintenance, proliferation and differentiation is under tight regulation as excess stem cell proliferation could facilitate tumour formation and conversely loss of stem cells or failure of differentiation could disrupt tissue homeostasis or repair. Hence, stem cells are regulated by multiple layers of molecular control and this volume discusses transcriptional, translational, epigenetic, cell signalling and microRNA modalities that affect stem cell behaviour. Many of the underlying key principles of stem cell biology were discovered by genetic analysis of invertebrate systems and chapters in this volume describe regulation of the germline in C. elegans and in the digestive system, central nervous system and germline of Drosophila. The molecular processes that regulate regenerative organ systems from all three of the vertebrate germ layers are described with emphasis on the male germline, nervous system, epidermis, intestine, haematopoietic system and derivatives of the mesoderm. Several chapters also focus on molecular families that have been implicated in controlling a range of stem cell types including the JAK-STAT, Wnt and Notch signalling pathways; Myc, Myb and nuclear receptor transcriptional regulators; the Musashi family of RNA-binding proteins; microRNAs and epigenetic regulators. This volume will provide access to the current state of re

The purpose of this publication is to introduce a new, simpler and more effective way in which to interpret pharmaceutical aerosol particle size data from orally inhaled products (OIPs). Currently, the compendial and regulatory requirements dictate the need for measurements by full resolution multi-stage cascade impactor (CI), a process that is demanding for the operator, time consuming, prone to experimental error, and challenging for method transfers from one laboratory to another. Furthermore, we shall show that the current practice of reducing information from mass-weighted aerodynamic particle size distribution (APSD) measurements through the use of CI stage groupings is not the most effective decision-making tool for OIP quality control (QC) in comparison with newly introduced, mutually-independent efficient data analysis (EDA) metrics that can be derived either from full resolution or abbreviated impactor measurements (AIM).

This book is an essential guide for those thinking of undertaking a multi-centre research project. Research across international boundaries presents challenges with the need to consider relevance of research objectives and feasibility of procedures in different settings whilst maintaining scientific integrity in terms of design, instruments and execution.

This book presents original results on the leading edge of cancer research. Chapter One summarizes what is currently known regarding the epigenetic regulation of osteosarcoma pathways and oncogenes, as well as clinical trials of drugs that exert epigenetic regulation. Chapter Two critically discusses the role of ECM-dependent signaling in osteosarcoma progression. Chapter Three illustrates the harmful effects of ultraviolet radiation exposure by focusing on photocarcinogenesis. Chapter Four examines the psychology of sunscreen use and outlines the key psychological factors associated with sunscreen use. Chapter Five reviews the cellular and molecular mechanism of Regulatory T cells (Tregs) and Transforming Growth Factor- mediating cervical cancer development. Chapter Six examines the affect of the American cranberry extract on expression of insulin-like growth factor-I and insulin-like growth factor binding proteins in human prostate cancer cells in vitro. Chapter Seven discusses the design of synthetic peptides to specifically interfere the papillomavirus binding factor/14-3-3beta binding to restore papillomavirus binding factor apoptotic functions. Chapter Eight examines brain development using correlations between Diffusion Kurtosis and neurite orientation dispersion and density imaging (NODDI) in neonates and young children. Chapter Nine highlights the opportunities that are available to prevent the late effects related to stress and fears, emphasizing the importance of teaching patients resiliency and how to cope.

This book contains an extensive collection of critical reviews, from leading researchers in the field of regulated protein degradation. It covers the role of regulated proteolysis in a range of microorganisms (from Gram positive, Gram negative and pathogenic bacteria to Archaea and the Baker s yeast Saccharomyces cerevisiae)."

The second edition maintains the standard of excellence established in the first edition, while adjusting the content to reflect changes in tissue optics and medical applications since 1995. The material concerning light propagation now contains new chapters devoted to electromagnetic theory for coherent light. The material concerning thermal laser-tissue interactions contains a new chapter on pulse ablation of tissue. The medical applications section now includes several new chapters on Optical Coherent Tomography, acoustic imaging, molecular imaging, forensic optics and nerve stimulation. A detailed overview is provided of the optical and thermal response of tissue to laser irradiation along with diagnostic and therapeutic examples including fiber optics. Sufficient theory is included in the book so that it is suitable for a one or two semester graduate or for senior elective courses. Material covered includes (1) light propagation and diagnostic application; (2) the thermal response of tissue and therapeutic application; (3) denaturation; and (4) ablation. The theory and applications provide researchers with sufficient detail that this volume will become the primary reference for laser-tissue interactions and medical applications.

Machine learning is a novel discipline concerned with the analysis of large and multiple variables data. It involves computationally intensive methods, like factor analysis, cluster analysis, and discriminant analysis. It is currently mainly the domain of computer scientists, and is already commonly used in social sciences, marketing research, operational research and applied sciences. It is virtually unused in clinical research. This is probably due to the traditional belief of clinicians in clinical trials where multiple variables are equally balanced by the randomization process and are not further taken into account. In contrast, modern computer data files often involve hundreds of variables like genes and other laboratory values, and computationally intensive methods are required. This book was written as a hand-hold presentation accessible to clinicians, and as a must-read publication for those new to the methods.

Adaptive Designs for Sequential Treatment Allocation presents a rigorous theoretical treatment of the results and mathematical foundation of adaptive design theory. The book focuses on designing sequential randomized experiments to compare two or more treatments incorporating information accrued along the way. The authors first introduce the terminology and statistical models most commonly used in comparative experiments. They then illustrate biased coin and urn designs that only take into account past treatment allocations as well as designs that use past data, such as sequential maximum likelihood and various types of doubly adaptive designs. The book also covers multipurpose adaptive experiments involving utilitarian choices and ethical issues. It ends with adaptive methods that include covariates in the design. The appendices present basic tools of optimal design theory and address Bayesian adaptive designs. This book helps readers fully understand the theoretical properties behind various adaptive designs. Readers are then equipped to choose the best design for their experiment.

This book is a self-contained introduction to Statistics, presented in the context of clinical trials and pharmaceutical drug development. It focuses on the statistical analyses most commonly used in drug development and is therefore an ideal introduction to pharmaceutical statistics. Instead of introducing a series of statistical techniques, the book's organizational structure follows the order in which numerical information and statistical analyses are used in trials and new drug development.All students taking classes in pharmaceutical sciences and clinical research need a solid knowledge and understanding of the nature, methods, application and importance of Statistics. They need to understand:why, and how data are collected in clinical trials; how these data are summarized and analyzed; what the results mean in the context of the clinical research question; and, how the results are communicated to regulatory agencies and to scientific and medical communities.This title therefore adopts a unique approach and concept in organization of the content. It begins with an introduction to statistical theory, analysis and interpretation. This is followed by a discussion of t-tests and confidence intervals. Readers are then taken through the whole process of new drug development (using one specific example throughout) that is meaningful in the context of their broader studies. Throughout this process, statistical techniques and analyses are introduced in the order in which they are employed during the process.The book's realistic scientific and progressive organization from pre-clinical trials to clinical pharmacology through clinical trials is novel, meaningful and educationally powerful. The book emphasises the importance of descriptive statistics as well as inferential statistics, something that is rarely done.Supplementary material is included for this text on the PharmPress website in the form of PowerPoint lecture notes on Statistics (based on content of this book) that can be downloaded by lecturers.

"Bioinformatics of Human Proteomics" discusses the development of methods, techniques and applications in the field of protein bioinformatics, an important direction in bioinformatics. It collects contributions from expert researchers in order to provide a practical guide to this complex field of study. The book covers the protein interaction network, drug discovery and development, the relationship between translational medicine and bioinformatics, and advances in proteomic methods, while also demonstrating important bioinformatics tools and methods available today for protein analysis, interpretation and predication. It is intended for experts or senior researchers in the fields of clinical research-related biostatistics, bioinformatics, computational biology, medicine, statistics, system biology, molecular diagnostics, biomarkers, or drug discovery and development. Dr.Xiangdong Wang works as a distinguished professor of Respiratory Medicine at Fudan University, Shanghai, China. He serves as Director of Biomedical Research Center, Fudan University Zhongshan Hospital and adjunct professor of Clinical Bioinformatics at Lund University, Sweden. His main research is focused on the role of clinical bioinformatics in the development of disease-specific biomarkers and dynamic network biomarkers, the molecular mechanism of organ dysfunction and potential therapies.

The health of the proteome depends upon protein quality control to regulate the proper synthesis, folding, translocation, and clearance of proteins. The cell is challenged constantly by environmental and physiological stress, aging, and the chronic expressions of disease associated misfolded proteins. Substantial evidence supports the hypothesis that the expression of damaged proteins initiates a cascade of molecular events that leads to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and other diseases of protein conformation.