This book presents the latest data from basic research and clinical trials supporting the effectiveness of ketamine as a treatment for depression, bipolar disorder, and suicidal behavior, setting these positive findings within the context of the serious problem of ketamine abuse. The first part of the book focuses on the evidence regarding ketamine abuse, with specific reference to Asian countries, and discusses countermeasures and complication management. It then addresses the mechanisms underlying the antidepressant and side effects of ketamine, which have remained elusive, describing and discussing important new research findings. Further, it explains insights gained from whole brain imaging in rodents and from behavioral pharmacology, and presents evidence regarding the role of gut microbiota, the NMDA receptor GluN2D subunit, and the lateral habenula in the actions of ketamine. These advances form the basis for the safer use of ketamine in patients with treatment-resistant depression and are expected to lead to the development of new antidepressants.

Olesja Rissling analyzes the potential interaction of mycophenolic acid (MPA) and pantoprazole. MPA is used as an immunosuppressive drug to prevent acute organ rejections after organ transplantation. Pantoprazole, known to interact with the bioavailability of drugs, is used to prevent upper gastrointestinal disorders. The author performed a clinical pharmacokinetic study in renal transplant patients to evaluate a potential interaction of MPA and pantoprazole. The bioavailability and the maximum concentration of MPA were determined with or without pantoprazole intake. An influence on the immunosuppressive effect was evaluated by measuring the target enzyme activity. Overall, no significant change in the bioavailability or the maximum concentration was found. Similar results were obtained for the target enzyme activity after pantoprazole intake with MPA. The results suggest that the interaction of pantoprazole with MPA does not compromise the immunosuppressive effect to a clinically meaningful extent.

In the last decade, a large number of major discoveries have shed light on the molecular mechanisms of lymphocyte migration and the anatomy of immune responses. In T-Cell Trafficking: Methods and Protocols, expert researchers explore how the development of novel and cutting-edge techniques, particularly in the field of real-time imaging and genetic manipulation, have led to an increased understanding of lymphocyte trafficking. Written by internationally recognized experts in their respective fields, chapters provide state-of-the-art protocols to study lymphocyte migration and T-cell: endothelial cell interactions in vitro, address various approaches used for direct visualization of the development of the lymphoid system, lymphocyte recirculation, and effector responses in experimental models in vivo, and explore lymphocyte migration and inflammation in the human system. Composed in the highly successful Methods in Molecular Biology (TM) series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Innovative and highly practical, T-Cell Trafficking: Methods and Protocols is an essential manual for newcomers in this ever-expanding and exciting area of research, as well as a valuable addition to more specialized laboratories.

This book demonstrates the potential of urine as a biomarker resource for early disease detection, covering the related theory, strategies, tools and findings. Biomarkers are measurable changes associated with diseases. Blood, as a critical part of its internal environment, is closely monitored and controlled by the body to maintain homeostasis, especially in the early stages of diseases. In contrast, urine, as a form of waste excreted by the body, collects a variety of substance changes. Accordingly, urine can offer an ideal resource for early biomarker discovery. In addition, urine is more stable than blood in vitro, and is easy to store and analyze. The book discusses exciting preliminary applications of urine biomarkers for diseases affecting major biological systems. Its main goal is to make scientists, clinicians and medical companies aware of this important, exciting, undeveloped, and profitable field.

The global medical process is a chain of different medical multidisciplinary procedures. The success in global Patient Safety will depend on the Safety of the consecutive medical processes that intervene in this complex system. Laboratory data is an essential part of health care, indeed it is used in 70% of clinical decisions. Inappropriate laboratory test over requesting is extremely frequent. The prevalence of under requesting has been less studied. The consequences of under requesting are clear, we are missing a diagnosis. Inappropriate over requesting can result not only in a problem of cost but also in a problem regarding patient safety. Additionally, another important consequence of inappropriate tests over requesting is that such amount of unnecessary tests has probably contributed to a significant increase in the volume of those over the last years. In all, there is general consensus that the inadequacy of test requesting must be corrected through strategies and monitored over time through indicators to assure the optimal laboratory contribution to clinical decision-making and patient safety.

This handbook is unique in its comprehensive coverage of the subject and focus on practical applications in diverse fields. It includes methods for sample preparation, the role of certified reference materials, calibration methods and statistical evaluation of the results. Problems concerning inorganic and bioinorganic speciation analysis, as well as special aspects such as trace analysis of noble metals, radionuclides and volatile organic compounds are also discussed. A significant part of the content presents applications of methods and procedures in medicine (metabolomics and therapeutic drug monitoring); pharmacy (the analysis of contaminants in drugs); studies of environmental samples; food samples and forensic analytics - essential examples that will also facilitate problem solving in related areas.

This book presents an overview of the most important current developments in the pre-analytical handling of tissue. It addresses in particular potential ways to improve the situation whereby methods employed in the pre-analytical phase – the period from surgical removal of tissue to the start of pathological processing – have remained essentially unchanged for decades with only modest standardization. It is examined how the pre-analytical period can be optimized, resulting not only in an increase in diagnostic quality but also in a reduction in processing time and costs. Among the key topics examined are the so-called cold ischemia time between tissue removal and fixation, the potential superiority of vacuum-based preservation over immediate formalin fixation, two-temperature fixation, molecular analysis methods, and the pre-analytics of specimens from particular tissues. Readers will find this book to be an important update that reveals the full importance of the pre-analytical phase for quality of pathological work-up.

Metastatic dissemination of cancer is a main cause of cancer related deaths, therefore biological mechanisms implicated in metastatic process presents an essential object of cancer research. This research requires creation and utilization of adequate laboratory models. The book describes main approaches to model processes of metastatic cancer dissemination and metastases development. The book is structured in according with various metastatic pathways reflecting molecular specificity of metastatic process as well as anatomical specificity of aria of dissemination. Each chapter is introduced by short discussion of clinical aspects of certain metastatic pathway. Especial attention is paid for methods of visualization, quantification and analysis of the modeled metastases. Additional chapter is devoted to methods of mathematic modeling of tumor spread. The data presented in the book may be helpful for cancer researchers and oncologists.

This volume provides a comprehensive, state-of-the art review in the field of experimental and human nephrogenesis. The book reviews new data on the effects on kidney development by neonatal asphyxia, obstructive uropathies, nephrotoxic drugs, malnutrition, underfeeding, overfeeding and provides all possible preventive measures to ensure the well-being of the kidney at birth. The book also discusses the possible implications between renal development and the insurgence of kidney disease in adult life and the correlation with renal carcinogenesis. Written by well recognized experts in their fields, Kidney Development in Renal Pathology is a valuable tool for pathologists, neonatologists, nephrologists, gynecologists and researchers with an interest in kidney diseases.

This thesis presents a theoretical and experimental approach for the rapid fabrication, optimization and testing of holographic sensors for the quantification of pH, organic solvents, metal cations, and glucose in solutions. Developing non-invasive and reusable diagnostics sensors that can be easily manufactured will support the monitoring of high-risk individuals in any clinical or point-of-care setting. Sensor fabrication approaches outlined include silver-halide chemistry, laser ablation and photopolymerization. The sensors employ off-axis Bragg diffraction gratings of ordered silver nanoparticles and localized refractive index changes in poly (2-hydroxyethyl methacrylate) and polyacrylamide films. The sensors exhibited reversible Bragg peak shifts, and diffracted the spectrum of narrow-band light over the wavelength range peak 495-1100 nm. Clinical trials of glucose sensors in the urine samples of diabetic patients demonstrated that they offer superior performance compared to commercial high-throughput urinalysis devices. Lastly, a generic smartphone application to quantify colorimetric tests was developed and tested for both Android and iOS operating systems. The sensing platform and smartphone application may have implications for the development of low-cost, reusable and equipment-free point-of-care diagnostic devices.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.

In Vitro Toxicology Systems brings together important issues and considerations needed in order to develop a workable, reliable, integrated testing strategy for the replacement of animals in toxicity testing regimes. This thorough volume includes sections on in vitro models for systemic organ toxicity, neurotoxicity, sensory organs, immunotoxicity and reproductive toxicity and addresses how stem cells may be used going forward. The book also tackles difficult areas of toxicology such as carcinogenicity and nanotoxicology, with additional chapters dedicated to kinetics, metabolism, and in vitro in vivo extrapolation. The book also addresses biological processes such as stress response pathways and mechanistic biomarkers and how these can be uncovered and measured using high content approaches. Reliable and authoritative, In Vitro Toxicology Systems will be of benefit not only to students, scientists and regulators working in the field of chemical safety assessment but also to a wider scientific audience.

The second volume of Behavioral Genetics of the Mouse provides a comprehensive overview of the major genetically modified mouse lines used to model human neurobehavioral disorders; from disorders of perception, of autonomous and motor functions to social and cognitive syndromes, drug abuse and dependence as well as neurodegenerative pathologies. Mouse models obtained with different types of genetic manipulations (i.e. transgenic, knockout/in mice) are described in their pathological phenotypes, with a special emphasis on behavioral abnormalities. The major results obtained with many of the existing models are discussed in depth highlighting their strengths and limitations. A lasting reference, the thorough reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.

Reflecting the development of powerful new tools and high-throughput methods to analyze adenoviral particles and their interactions with host cells, the third edition of Adenovirus Methods and Protocols calls upon experts in the field to convey advances in molecular biology, genomics and proteomics, imaging, and bioinformatics. Beginning with cryo-electron microscopy, atomic force microscopy, and mass spectrometry for a high resolution image and characterization of the virion, this detailed book then continues with capsid modifications and viral-like particles as promising alternatives to classical adenovirus vectors, and the study of adenovirus in host interactions in vitro at the cellular level as well as in vivo in animal models. Finally, the volume concludes with an extensive update of the most efficient protocols to generate, amplify, and/or purify, at small and large scale, standard human Ad5 as well as non-human, chimeric, and helper-dependent adenovirus vectors. Written in the greatly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Adenovirus Methods and Protocols, Third Edition serves as an ideal guide for scientists continuing to research this highly valuable viral tool.

This book provides a comprehensive, state-of-the art review of the genitourinary tumor pathology field and the most contemporary insights regarding specimen submission, histologic morphology, immunohistochemistry, and molecular studies useful in the diagnosis of genitourinary neoplasms. Discussion of the clinical implications of pathological findings is contributed by renowned clinicians in the field. This handsome volume guides the reader through the intricacies of genitourinary tumor pathology, diagnosis, reporting, and prognosis. Written by experts in the field, Genitourinary Pathology: Practical Advances is of great value to anatomic pathologists, urologists, fellows in genitourinary pathology, as well as upper level residents training in pathology.

Tissue diagnosis in surgical pathology is the most important determinant of patient outcomes in oncology and other medical conditions. An appropriate diagnosis of a tumor correctly determines the necessary therapy for that patient. Error Reduction and Prevention in Surgical Pathology focuses on how errors happen, the best systems to detect errors and the best systems to prevent errors. As with any form of testing, the test cycle in surgical pathology can be divided into pre-analytic (collection and handling of specimens), analytic (the actual determination of disease or other diagnostic information) and post-analytic (generation of reports and distribution). Error can occur anywhere in the process and all of these steps must be performed optimally so that the correct diagnosis is made and delivered. Error Reduction and Prevention in Surgical Pathology serves as an essential guide to a successfully managed laboratory and contains all relevant information needed to manage patients and deliver the best diagnosis.

Somuchofwhatweknowaboutthepathogenesisofhumandiseasehascomefromthe systematic and careful study of histological material. Indeed, every internal medicine discipline has its landmark papers describing the clinico-pathological correlations. However, increasingly, it is molecular and cellular biology that provides the necessary mechanistic insights. For many years, it was thought that the two skill sets were mutually exclusive, but we hope that this book shows that this is not necessarily so. Implicitinthescienceofhistologyisthepreservationandarchivingoftissue.PartIof the book concentrates on the preparation of tissue, providing an overview of fixation, embedding, and processing (Chapter 1), and in Chapters 2 and 3, the required techniques for the retrieval of RNA from histological sections. Both routine and specialist histological staining techniques are provided in Part II. These include pro- cols for immuno (Chapters 4-7), lectin (Chapter 8), and hybridization (Chapter 9) histochemistry,histologicalstaining (Chapters10and11),aswellasspecificmethods for the in situ identification of hypoxia (Chapter 12) and apoptosis (Chapter 13). Finally, Part III details advances in imaging (Chapters 14-16) and image analysis (Chapter 17). It is hoped that this volume will provide molecular biologists with the basic his- chemical techniques and histologists with the molecular techniques to realise the potential of their resource. We are indebted to the authors for their generosity in sharing these protocols.

Clostridium difficile, a major nosocomial pathogen shown to be a primary cause of antibiotic-associated disease, has emerged as a highly transmissible and frequently antibiotic-resistant organism, causing a considerable burden on health care systems worldwide. In Clostridium difficile: Methods and Protocols, expert researchers bring together the most recently developed methods for studying the organism, including techniques involving isolation, molecular typing, genomics, genetic manipulation, and the use of animal models. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes highlighting tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Clostridium difficile: Methods and Protocols serves as an ideal guide for scientists now in a position to gain an in-depth understanding of how this organism is transmitted and how it causes disease.

Despite the many milestones in cystic fibrosis (CF) research, progress toward curing the disease has been slow, and it is increasingly difficult to grasp and use the already wide and still growing range of diverse methods currently employed to study CF so as to understand it in its multidisciplinary nature. Cystic Fibrosis: Diagnosis and Protocols aims to provide the CF research community and related researchers with a very wide range of high-quality experimental tools, as an easy way to grasp and use classical and novel methods applied to cystic fibrosis. Volume II: Methods and Resources to Understand Cystic Fibrosis focuses on pathophysiology, Omics approaches, and a variety of key resources recently made available for CF research. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Cystic Fibrosis: Diagnosis and Protocols will provide readers with optimal working tools to address pressing questions in the best technical way, while helping all of us, as a research and clinical community, to move faster hand-in-hand toward unravelling the secrets of this challenging disorder and cure it.

Research in the pharmaceutical sciences and medicinal chemistry has taken an important new direction in the past two decades with a focus on large molecules, especially peptides and proteins, as well as DNA therapeutics. In Drug Design and Discovery: Methods and Protocols, leading experts provide an in-depth view of key protocols that are commonly used in drug discovery laboratories. Covering both classic and cutting-edge techniques, this volume explores computational docking, quantitative structure-activity relationship (QSAR), peptide synthesis, labeling of peptides and proteins with fluorescent labels, DNA-microarray, zebrafish model for drug screening, and other analytical screening and biological assays that are routinely used during the drug discovery process. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and accessible, Drug Design and Discovery: Methods and Protocols serve as a vital laboratory reference for pharmaceutical chemists, medicinal chemists, and pharmacologists as well as for molecular biologists.

Presenting the most up-to-date techniques for the detection, genotyping, and investigation of methicillin-resistant S. aureus (MRSA), this second edition of Methicillin-Resistant Staphylococcus aureus (MRSA) Protocols collects chapters that utilize the power of complete genomic sequences and advanced high-throughput technologies that have pushed this field to its present state. These enable the development of specific and rapid diagnosis methods, the investigation and elucidation of mechanisms of bacterial evolution to antibiotic resistance and pathogenicity, and the identification of novel targets to develop more potent therapeutic and/or preventive agents. Written for the Methods in Molecular Biology series, numerous 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. Authoritative and fully updated, Methicillin-Resistant Staphylococcus aureus (MRSA) Protocols, Second Edition serves as a key reference for researchers attempting to set up a new method to study MRSA or even for technicians and scientists working on other pathogens.

Enzyme-linked immunospot assay (ELISPOT) has been known for some time as a unique state-of-the-art technique for studying the cytokine-secreting activity of immune system cells, and it appears to be one of the fast growing applications in biomedical research, becoming an indispensable tool in vaccine development, HIV research, transplantation studies, and cancer and allergy research. The second edition of Handbook of ELISPOT: Methods and Protocols, only the second book in the field which is entirely dedicated to ELISPOT assay, shares the detailed techniques that have been developed since the release of the popular first edition. Straight from the labs of seasoned experts, this book covers setting and performing ELISPOT assays, ELISPOT for veterinary research, advanced ELISPOT techniques, image and data analysis, as well as vaccine development and diagnostics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective chapters, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Handbook of ELISPOT: Methods and Protocols, Second Edition serves as a compilation of a technical reference and a troubleshooting guide for researchers, both experienced and novice, worldwide in order to advance the usage of this key tool.

Renal Neoplasms: An Integrative Approach to Cytopathologic Diagnosis provides a comprehensive review of cytology and all the morphologic correlates, including their respective limitations, related to a broad spectrum of renal neoplasms with special emphasis on cyto-histo correlation. The book also discusses related usual radiologic appearances, gross features and possible targeted therapies where appropriate. The volume features an integrated approach that provides step-by-step guidance in the morphologic evaluation of renal neoplasms. Furthermore, all chapters are written by experts who deal with this type of specimen in their daily practice and have insights into the pathology as well as the clinical aspects of these tumors. Illustrated with high quality color microphotographs and formatted for ease of use in the lab, Renal Neoplasms: An Integrative Approach to Cytopathologic Diagnosis is a helpful guide to everyday pathology practice, especially for pathologists who rarely encounter this type of specimen.

As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. Written in the highly 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 laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field.

Adverse drug reactions and interactions are still a major headache for healthcare professionals around the world. The US Food and Drug Administration's database recorded almost 300,000 serious adverse events in 2009 alone, of which 45,000 instances proved fatal. This updated new edition of the indispensable guide to drug interactions incorporates fresh research completed since the book's original publication by Humana Press in 2004. Additions include a new section on pharmacogenomics, a rapidly growing field that explores the genetic basis for the variability of responses to drugs. This new material reviews important polymorphisms in drug metabolizing enzymes and applies the findings to forensic interpretation, using case studies involving opiates as exemplars. Existing chapters from the first edition have in most cases been updated and reworked to reflect new data or incorporate better tables and diagrams, as well as to include recent drugs and formulations. Recent references have been inserted too. The handbook features extra material on illicit drug use, with a new chapter tackling the subject that covers cocaine, amphetamines and cannabis, among others. The section on the central nervous system also deals with a number of drugs that are abused illicitly, such as benzodiazepines, opiates flunitrazepam and GHB, while so-called 'social' drugs such as alcohol and nicotine are still discussed in the book's section on environmental and social pharmacology. Focusing as before on detailed explanation and incorporating both pharmacokinetic and pharmacodynamic drug interactions, this book will continue to be a lodestar for health and forensic professionals as well as students.