When Ehrlich discovered the first evidence of the blood-brain barrier in 1885, he probably did not perceive the Great Wall that remained hidden from consciousness inside the central nervous system. Ehrlich had observed that acidic vital dyes did not stain the brain if they were injected into the blood stream. A century ago (1913), Goldman showed that the injection of trypan blue in the cerebrospinal fluid stained only the brain, but not the other organs. For almost a century it was thought that the blood-brain barrier (BBB) consisted in a physical barrier, resulting from the restricted permeability of the cerebral endothelial cell layer, as they are joined by tight junctions. However, as scientists are always looking for news in what is already discovered, in the end of the 20th century we had evidences that cerebral endothelial and glial cells express several drug metabolizing enzymes consisting in a second protection system: a metabolic barrier. Furthermore, the drugs and their metabolites must overcome the activity of several multidrug resistance proteins that function as ATP-dependent efflux pumps, consisting in the third line of defence: the active barrier. Therefore, the way the BBB actually works should be better explained. Several endogenous compounds, as well as xenobiotics, may be activated by enzymes of the metabolic barrier, generating reactive oxygen species that could damage neurons. Therefore, endothelial and glial cells possess endogenous protecting compounds and enzymes against oxidants, consisting in an antioxidant barrier. When all these systems fail, glial cells, mainly microglia, secrete cytokines in an attempt to crosstalk with defence cells asking for help, which consists in an immune barrier. In cerebral regions that are devoid of the physical barrier, such as circumventricular organs, the metabolic, active, antioxidant and immune barriers are reinforced. It is important to understand how cells involved in the BBB interact with one another and the dynamic mechanisms of their functions. This Research Topic published in this e-Book considers recent highlights in BBB structure, cell and molecular biology, biotransformation, physiology, pathology, pharmacology, immunology and how these basic knowledges can be applied in drug discovery and clinical researches, rewriting what is already written, and paving the way that goes to the Great Wall in the Frontiers of the Brain in this new century that is just beginning.

The state of health care is reflected by perinatal and neonatal morbidity and mortality as well as by the frequencies of long-term neurologic and developmental disorders. Many factors, some without immediately rec ognizable significance to childbearing and many still unknown, undoubt edly contribute beneficially or adversely to the outcome of pregnancy. Knowledge concerning the impact of such factors on the fetus and sur viving infant is critical. Confounding analyses of pregnancy outcome, especially these past two or three decades, are the effects of newly un dertaken invasive or inactive therapeutic approaches coupled with the advent of high technology. Many innovations have been introduced with out serious efforts to evaluate their impact prospectively and objectively. The consequences of therapeutic misadventures characterized the past; it seems they have been replaced to a degree by some of the complications of applied technology. Examples abound: after overuse of oxygen was recognized to cause retrolental fibroplasia, its restriction led to an in crease in both neonatal death rates and neurologic damage in surviving infants. Administration of vitamin K to prevent neonatal hemorrhagic disease, particularly when given in what we now know as excessive dos age, occasionally resulted in kernicterus. Prophylactic sulfonamide use had a similar end result. More recent is the observation of bronchopul monary dysplasia as a complication of respirator therapy for hyaline membrane disease.

This handbook reviews promising applications of psychedelics in treatment of such challenging psychiatric problems as posttraumatic stress disorder, major depression, substance use disorders, and end-of-life anxiety. Experts from multiple disciplines synthesize current knowledge on psilocybin, MDMA, ketamine, and other medical hallucinogens. The volume comprehensively examines these substances' neurobiological mechanisms, clinical effects, therapeutic potential, risks, and anthropological and historical contexts. Coverage ranges from basic science to practical clinical considerations, including patient screening and selection, dosages and routes of administration, how psychedelic-assisted sessions are structured and conducted, and management of adverse reactions.

- Volume is divided into four sections, allowing easy navagation for researchers and practicing physicians - Text includes clinical trials - Written by leaders in the field

The medical use of marijuana is surrounded by a cloud of social, political, and religious controversy, which obscures the facts that should be considered in the debate. This book summarizes what we know about marijuana from evidence-based medicineâ€"the harm it may do and the relief it may bring to patients. The book helps the reader understand not only what science has to say about medical marijuana but also the logic behind the scientific conclusions. Marijuana and Medicine addresses the science base and the therapeutic effects of marijuana use for medical conditions such as glaucoma and multiple sclerosis. It covers marijuana's mechanism of action, acute and chronic effects on health and behavior, potential adverse effects, efficacy of different delivery systems, analysis of the data about marijuana as a gateway drug, and the prospects for developing cannabinoid drugs. The book evaluates how well marijuana meets accepted standards for medicine and considers the conclusions of other blue-ribbon panels. Full of useful facts, this volume will be important to anyone interested in informed debate about the medical use of marijuana: advocates and opponents as well as policymakers, regulators, and health care providers.

Whether the question is one of basic cell survival, or whether it is being used to correlate cell number to some other factor such as matrix synthesis, an estimate of cell viability is universally required. In Mammalian Cell Viability: Methods and Protocols, experts in the field describe methods from the most basic which can be performed in any laboratory, to some which require specific pieces of equipment. Initially focusing on methods for monolayer and suspension cells, later chapters describe methods for determining viability within tissue sections and 3 dimensional culture systems. Finally, methods requiring highly specialized equipment are described in order to explain what is possible. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting and avoiding known pitfalls. Practical and adaptable, Mammalian Cell Viability: Methods and Protocols serves as a self-contained laboratory manual useful to both experienced researchers and those new to this incredibly important and influential field.

Zebrafish: Methods for Assessing Drug Safety and Toxicity offers a practical guide for using zebrafish as a tool for toxicology studies. Consolidating key protocols and approaches to help researchers navigate the important and evolving field of zebrafish models for toxicity screening, this new title describes the methods for using the zebrafish as a model organism to assess compound-induced toxicity on all major organs. Individual chapters that concentrate on assays for each organ system are included and various analytical tools including microscopy, microplate readers, high content imaging systems, ECG, blood pressure monitors, high speed video and motion detectors are described.

Fixatives and Methods of Fixation, Tissue Processing, Theory of Staining, Decalcification, Preparation of Stains, Mountants, Frozen Methods, Carbohydrates, Protein, Amyloids, Nucleic Acids, Lipids, Pigments, Minerals, Microorganisms in Sections, Enzymes, Connective Tissue, Neurological Studies, Endocrine Glands, Microwave Histology, Ultrahistochemistry, Techniques in Cell Biology, Methods for Special Organs, Invertebrate Staining Methods, Mast Cells, Immunocytochemistry.

This basic text introduces the reader to all facets of pediatric imaging from the importance of understanding X-ray exposure to children through the appropriate indications for ordering a particular examination. It covers basic problems in each organ system. There is a quiz after most of the clinical chapters. The text is aimed at the novice, while the pictures of classic important imaging findings are designed to test the mature pediatric caregiver and the radiologist beginning training. The information conveyed in this text is essential for pediatric house staff, entering radiology residents, pediatric nurse practitioners, emergency room physicians, and practicing pediatricians. It will be valuable to all physicians who deal with children as a segment of their practice. This book serves as the basic text for any of the above individuals taking a rotation through a pediatric imaging department and for orienting pediatric personnel within the imaging department.

Prostate cancer is by far the most common cancer in men and the second leading cause of death due to cancer. It comprises a mixed group of tumours displaying varying clinical behaviour: while some have a very aggressive course, others are rather indolent. Prevention of prostate cancer and discrimination between aggressive and indolent forms are important clinical goals and the acquisition of significant new evidence on means of achieving these aims makes this book particularly timely. A wide range of topics are covered by leading authorities in the field. The biology and natural history of prostate cancer are reviewed and the role of lifestyle and dietary factors, assessed. Detailed attention is paid to risk prediction biomarkers and to the role of novel high-throughput nucleic acid-based technologies in improving risk prediction and thereby allowing tailored approaches to cancer prevention. Potential means of chemoprevention of prostate cancer are also reviewed in depth, covering the very positive new data on the impact of aspirin as well as evidence regarding 5α-reductase inhibitors, DFMO and lycopene. Guidance is provided on the differentiation of aggressive from indolent disease and the policy and research implications of recent findings are examined. This book will be of interest to both clinicians and researchers.