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The discovery and development of a biological active molecule with therapeutic properties is an ever increasing complex task, highly unpredictable at the early stages and marked, in the end, by high rates of failure. As a consequence, the overall process leading to the production of a successful drug is very costly. The improvement of the net outcome in drug discovery and development would require, amongst other important factors, a good understanding of the molecular events that characterize the disease or pathology in order to better identify likely targets of interest, to optimize the interaction of an active agent (small molecule or macromolecule of natural or synthetic origin) with those targets, and to facilitate the study of the pharmacokinetics, pharmacodynamics and toxicity of an active agent in suitable models and in human subjects. The objective of this Research Topic is to highlight new developments and applications of imaging techniques with the objective of performing pharmacological studies in vivo, in animal models and in humans. In the domain of drug discovery, the pharmacological and biomedical questions constitute the center of attention. In this sense, it is fundamental to keep in mind the strengths and limitations of each analytical or imaging technique. At the end, the judicious application of the technique with the aim of supporting the search for answers to manifold questions arising during a long and painstaking path provides a continuous role for imaging within the complex area of drug discovery and development.
This volume presents classical approaches to in vivo neuropharmacology and neurophysiology, such as c-fos, electrochemistry, microdialysis microstimulation, and push-up superfusion. It also explores exciting new methods for behavioral analysis, and techniques based on optogenetics and non-invasive magnetic resonance imaging. The chapters of this book cover topics such as principles of stereotaxy, pharmaco-based fMRI and neurophysiology in humans and non-human primates, electrical nerve stimulation and central microstimulation, involvement of neurotransmitters in mnemonic processes, the impact of cannabinoids on motor activity, as well as the involvement of nitric oxide in neurotoxicity produced by psychostimulant drugs. Each chapter also discusses difficulties, tips, tricks, and precautions to take. Neuromethods series style chapters include the kind of detail and key advice from the specialists needed to get successful results in your own laboratory. Cutting-edge and practical, In Vivo Neuropharmacology and Neurophysiology is a valuable resource for experienced and less experienced investigators of brain function and brain disorders.
Imaging Drug Action in the Brain is an outstanding reference that provides detailed methodological information and presents a current review of information obtained using various methods to delineate the neuroanatomy of drug action. It presents material covering selective lesioning and intracranial injections in intact animals. It examines various applications of receptor binding techniques and their importance in pharmacology. In vivo metabolic mapping studies to delineate the distributions of action of psychoactive drugs in animals are reviewed in detail. Imaging Drug Action in the Brain presents recent advances in extending these types of studies to human investigations, using positron emission tomography (PET) scanning and electrophysiological imaging techniques. Applications of immunocytochemical and molecular biology techniques in studies of drug action are explained. Imaging Drug Action in the Brain is the only book that encompasses all of these techniques with up-to-date examples of their applications. It is an essential resource for researchers in the fields of neuropharmacology, neuroanatomy, neurophysiology, and nuclear medicine.
This open access book, published under a CC BY 4.0 license in the Pubmed indexed book series Handbook of Experimental Pharmacology, provides up-to-date information on best practice to improve experimental design and quality of research in non-clinical pharmacology and biomedicine.
This textbook is a practical guide to the use of small animal imaging in preclinical research that will assist in the choice of imaging modality and contrast agent and in study design, experimental setup, and data evaluation. All established imaging modalities are discussed in detail, with the assistance of numerous informative illustrations. While the focus of the new edition remains on practical basics, it has been updated to encompass a variety of emerging imaging modalities, methods, and applications. Additional useful hints are also supplied on the installation of a small animal unit, study planning, animal handling, and cost-effective performance of small animal imaging. Cross-calibration methods and data postprocessing are considered in depth. This new edition of Small Animal Imaging will be an invaluable aid for researchers, students, and technicians involved in research into and applications of small animal imaging.
The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation.
This book provides a comprehensive view of the methodologies used for the study of liver toxicity encountered throughout the whole life cycle of a drug, from drug discovery, to clinical trial, post-marketing, and even clinical practice. Organized into six sections, the first section introduces the mechanisms contributing to drug-induced liver toxicity. The second and third section explore in silico and in vitro approaches used to help mitigate hepatotoxicity liability at the early stages of drug development. The fourth section describes methodologies applied in regulatory processes, including preclinical studies, clinical trials, and post-marketing surveillance. The fifth section discusses clinical hepatotoxicity. Emerging technologies are examined in the final section. As a volume in the Methods in Pharmacology and Toxicology series, chapters include the kind of expert advice that will lead to optimal results. Authoritative and practical, Drug-Induced Liver Toxicity serves all those who aim to improve assessment and understanding of hepatotoxic potentials of new medications and marketed drugs. Chapter 30 is open access under a CC BY 4.0 license via link.springer.com.
Advanced Issue Resolution in Safety Pharmacology not only discusses unique issues that may emerge during the development of new medicines, but also provides detailed insights on how to resolve them. The book employs a valuable strategy that integrates preclinical findings with the clinical resolution of those findings. In addition, it introduces key interdisciplinary topics in an accessible and systematic format. Edited and written by leaders in the field of safety pharmacology, this book considerably advances the discussion on issue resolution topics, thus raising them to the next level of importance by providing scientists with an indispensable resource on solving safety issues.
The most comprehensive reference on fluorescent nanodiamond physical and chemical properties and contemporary applications Fluorescent nanodiamonds (FNDs) have drawn a great deal of attention over the past several years, and their applications and development potential are proving to be manifold and vast. The first and only book of its kind, Fluorescent Nanodiamonds is a comprehensive guide to the basic science and technical information needed to fully understand the fundamentals of FNDs and their potential applications across an array of domains. In demonstrating the importance of FNDs in biological applications, the authors bring together all relevant chemistry, physics, materials science and biology. Nanodiamonds are produced by powerful cataclysmic events such as explosions, volcanic eruptions and meteorite impacts. They also can be created in the lab by high-pressure high-temperature treatment of graphite or detonating an explosive in a reactor vessel. A single imperfection can give a nanodiamond a specific, isolated color center which allows it to function as a single, trapped atom. Much smaller than the thickness of a human hair, a nanodiamond can have a huge surface area that allows it to bond with a variety of other materials. Because of their non-toxicity, nanodiamonds may be useful in biomedical applications, such as drug delivery and gene therapy. The most comprehensive reference on a topic of rapidly increasing interest among academic and industrial researchers across an array of fields Includes numerous case studies and practical examples from many areas of research and industrial applications, as well as fascinating and instructive historical perspectives Each chapter addresses, in-depth, a single integral topic including the fundamental properties, synthesis, mechanisms and functionalisation of FNDs The first book published by the key patent holder with his research group in the field of FNDs Fluorescent Nanodiamonds is an important working resource for a broad range of scientists and engineers in industry and academia. It will also be a welcome reference for instructors in chemistry, physics, materials science, biology and related fields.
In Tumor Targeting in Cancer Therapy, Dr. Michel Pagé and a panel of authoritative experts from the drug industry, clinics, and academia introduce the principles and techniques of tumor targeting and critically survey their applications from laboratory to bedside. By concisely synthesizing the many technical details, the authors illuminate this innovative technique, ranging from the fundamentals of drug targeting and in vivo and in vitro experimentation, to such emerging therapeutic uses as radioimmunotherapy, radioimmunodetection, therapy with cytotoxic antibodies, immunotoxins, enzyme prodrug immunotherapy, and immunotherapeutics with fusion proteins. There are also reviews of targeting tumors with radioimmunoconjugates, photodynamic therapy, and magnetic drugs, as well as discussions of the internalization of antibodies, bioconjugation and biodistribution, the use of cytotoxic drugs, and the pros and cons of targeting by antibody or ligand.