Peptide And Amino Acid Transport Mechanisms In The Central Nervous System
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Peptide and Amino Acid Transport Mechanisms in the Central Nervous System by Ljubiša Rakić Pdf
Addresses the regulation, within the brain extracellular fluid, of peptide and amino acid levels, particularly neurotransmitters and neuromodulators. Particular attention is devoted to the way in which peptides may either penetrate the blood-brain barrier or alter its permeability to other solutes. Focuses on central nervous system disease, especially in designing drugs and agents which will penetrate the blood-brain barrier and expert central nervous actions. Annotation copyrighted by Book News, Inc., Portland, OR
Peptide Transport and Delivery into the Central Nervous System by Laszlo Prokai,Katalin Prokai-Tatrai Pdf
Hypo- or hypersecretion, alteration in storage, release, catabolism, and post-translational processing of neuropeptides are associated with the etiology of many diseases affecting the central nervous system (CNS). Various peptides native to the brain and the spinal cord, as well as various synthetic peptides, peptide analogues and peptidomimetics developed as their agonists or antagonists could be useful in the treatment of these CNS maladies. However, peptides face a formidable obstacle in reaching the intended site of action due to the existence of the blood-brain barrier (BBB), a vital element in the regulation of the internal environment of the brain and the spinal cord. After reviews on the role and neuropharmaceutical potential of peptides, properties of the BBB in the context of peptide transport in the CNS and potential transport mechanisms to cross the BBB, this volume discusses the development, present state-of-the-art and future trends of various strategies to overcome this major obstacle to peptide pharmacotherapy involving the CNS. Chapters are devoted to cover invasive approaches that circumvent the BBB by direct administration into the brain or the spinal cord and by transiently opening the tight junctions of or permeabilizing the endothelial cells separating the systemic circulation from the interstitial fluid of the CNS. Subsequently, physiologically based strategies that utilize biological carriers to gain access to the CNS are discussed in detail, followed by methods encompassing prodrug and chemical delivery/targeting strategies, which aim at altering the properties of the peptide to enhance BBB transport, and drug delivery strategies based on peptide vectors. Finally, a comparative evaluation on the present status and perspectives of the techniques is presented.
The Blood-Brain Barrier, Amino Acids and Peptides by Malcolm Beverley Segal,Berislav V. Zlokovic Pdf
Definition of the barrier The interstitial fluid (rSF) of the brain is separated from the blood by the blood-brain barrier (BBB). This barrier must not be thought of as a single entity or as an absolute restriction to all molecules, but as a multiple structure located at several sites within the brain. The first of these interfaces is located at the endothelium of the brain capillaries. Secondly there is a potential site for interchange on the outer linings of the brain between the dura and the arachnoid membranes. Thirdly, there are the choroid plexuses and the cerebrospinal fluid (CSF) which is in contact with the very permeable internal ependymal lining of the brain (Figure 1. 1). Finally there are areas of the brain which lack a blood-brain barrier. These areas constitute the circumventricu lar organs and have leaky capillaries with a barrier at the ependyma which limits the spread of molecules from those regions (Figure 1. 2). Each of these BBB sites has its own characteristic permeability and transport functions. We will now consider the properties of each of these barrier sites between the blood and the brain. THE CEREBRAL CAPILLARY ENDOTHELIUM Morphology This interface has both the largest surface area and the shortest path length between the blood and the brain rSF. The cerebral capillaries, which at first sight seem little different from the rest of the systemic circulation, are in fact unique to the brain.
Institute of Medicine,Committee on Military Nutrition Research
Author : Institute of Medicine,Committee on Military Nutrition Research Publisher : National Academies Press Page : 448 pages File Size : 52,6 Mb Release : 1999-09-15 Category : Technology & Engineering ISBN : 9780309172813
The Role of Protein and Amino Acids in Sustaining and Enhancing Performance by Institute of Medicine,Committee on Military Nutrition Research Pdf
It is a commonly held belief that athletes, particularly body builders, have greater requirements for dietary protein than sedentary individuals. However, the evidence in support of this contention is controversial. This book is the latest in a series of publications designed to inform both civilian and military scientists and personnel about issues related to nutrition and military service. Among the many other stressors they experience, soldiers face unique nutritional demands during combat. Of particular concern is the role that dietary protein might play in controlling muscle mass and strength, response to injury and infection, and cognitive performance. The first part of the book contains the committee's summary of the workshop, responses to the Army's questions, conclusions, and recommendations. The remainder of the book contains papers contributed by speakers at the workshop on such topics as, the effects of aging and hormones on regulation of muscle mass and function, alterations in protein metabolism due to the stress of injury or infection, the role of individual amino acids, the components of proteins, as neurotransmitters, hormones, and modulators of various physiological processes, and the efficacy and safety considerations associated with dietary supplements aimed at enhancing performance.
Transport Phenomena in the Nervous System by Giulio Levi,Leontino Battistin,Abel Lajtha Pdf
It is more recently becoming increasingly clear, however, that the homeostatic equilibrium, and its physiological and pathological changes, are governed by a complex set of mechanisms residing heterogeneously in a complex set of membranes. Mechanisms residing in the capillary endothelium are of importance - especially in short term penetration studies of administered substances from blood to brain; the physiological and pathological equilibria are likely to be more influenced and governed by mechanisms residing in neuronal, glial, nuclear, and lysosomal membranes, to name a few. For functional importance in turn, mechanisms residing in mitochondrial and synaptosomal membranes are of crucial importance, for transport out of the system those present in choroid plexus among others have to be studied.
Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders
Author : Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders Publisher : National Academies Press Page : 74 pages File Size : 51,8 Mb Release : 2011-07-05 Category : Medical ISBN : 9780309212243
Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System by Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders Pdf
Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.
The Blood-Brain Barrier, Amino Acids and Peptides by M. Segal,Berislav V. Zlokovic Pdf
Definition of the barrier The interstitial fluid (rSF) of the brain is separated from the blood by the blood-brain barrier (BBB). This barrier must not be thought of as a single entity or as an absolute restriction to all molecules, but as a multiple structure located at several sites within the brain. The first of these interfaces is located at the endothelium of the brain capillaries. Secondly there is a potential site for interchange on the outer linings of the brain between the dura and the arachnoid membranes. Thirdly, there are the choroid plexuses and the cerebrospinal fluid (CSF) which is in contact with the very permeable internal ependymal lining of the brain (Figure 1. 1). Finally there are areas of the brain which lack a blood-brain barrier. These areas constitute the circumventricu lar organs and have leaky capillaries with a barrier at the ependyma which limits the spread of molecules from those regions (Figure 1. 2). Each of these BBB sites has its own characteristic permeability and transport functions. We will now consider the properties of each of these barrier sites between the blood and the brain. THE CEREBRAL CAPILLARY ENDOTHELIUM Morphology This interface has both the largest surface area and the shortest path length between the blood and the brain rSF. The cerebral capillaries, which at first sight seem little different from the rest of the systemic circulation, are in fact unique to the brain.
Metabolic Reactions in the Nervous System by Abel Lajtha Pdf
When the projected volumes of the Handbook are completed, most of our current knowledge of the biochemistry of nervous systems will have been touched upon. A number of the chapters will have dealt with the correlations of the biochemical findings with morphological and physio logical parameters as well. Considering the abysmal lack of such attempts, even in the recent past, this is a sign of great progress. If the reader's eventual goal is to derive the "laws" that relate various aspects of animal and human behavior to underlying physiological and biochemical function, these admirable volumes will help him to establish a firm biochemical base from which to operate. It is certain that the future approaches to the various problems of the information-processing functions of the nervous system will require an integrated understanding of the essence of all of the scientific disciplines which are grouped under the general name of neuro biology. The rich feast of information offered up in this Handbook will enable those in the non-chemical disciplines to pick and choose those areas of chemical information pertinent to their immediate interests. Similar types of compendia by physiologists, anatomists, cyberneticists, and psychologists have been helpful to chemists and continue to be so.
Circulating Regulatory Factors and Neuroendocrine Function by Daniela Jezová,John C. Porter Pdf
During the past several decades, much research effort has gone into the elucidation of the role of neuroendocrine systems as secretory and metabolic regulators of cells of a variety of organs and structures, including the testes, ovaries, adrenals, thyroid, pituitary gland, and mammary glands. However, the role of cells comprising such organs and structures in the modulation of neuroendocrine processes has received considerably less is generally less well appreciated. attention and Nonetheless, it is important that we understand the actions on neuroendocrine systems of substances that reach the brain by way of the vasculature, including hormones, cytokines, toxins, amino acids, drugs, and similar agents. In order to analyze the present state of knowledge on this topic, experimental scientists and clinicians, whose shared interests include actions of circulating agents on the brain, met at a satellite symposium of the XXXI International Congress of Physiological Sciences. This symposium, entitled Circulating Regulatory Factors and Neuroendocrine Function, was held in Smolenice Castle, Czechoslovakia, June 26-July 1, 1989, and reviews delivered at this symposium as invited presentations are published in this volume. Presentations given as free communications have been published separately and are available in Endocrinologia Experimentalis 24: 1-273, 1990.
An Introduction to the Blood-brain Barrier by Davson Pdf
This book is devoted to exploring the complexities of the blood-brain barrier. The book begins by reviewing the historical experiments that led to the concept of a barrier protecting the brain from variations in the blood. Transport kinetics and carrier-mediated processes are described, and the mechanism by which molecules can cross the barrier is discussed. Ways in which the barrier can be disrupted and opened are covered as well. Subsequent chapters in the book describe the transport of glucose and amino acids into the central nervous systems, cover recent findings by which peptides and proteins are able to gain entry or are excluded from the brain, and analyze models that can be used for investigating how the blood-brain barrier can be disordered in neurological disease processes.
Physiology and Pharmacology of the Blood-Brain Barrier by Michael W.B. Bradbury Pdf
The blood-brain barrier is still not completely understood and therefore the subject of fascinating study. How are endogenous substances transported through the blood-brain barrier? What are the known therapeutic and toxic agents? How are they transported across cerebral microvessels? The discussion of these and other questions with far-reaching consequences for all neuroscientists can be found in this volume. This authoritative and up-to-date review of the blood-brain barrier gives a proper understanding of the topic. The experimental principles, the results of very recent research, as well as the implications that experimental research has for clinical treatment are thoroughly covered. Information is given on: - new findings based on classical physiological and pharmacological techniques, - results obtained from brain capillaries in vitro and in culture, - results obtained from the new scanning techniques (PET and MRI), - the immunology of the blood-brain barrier, - trace metal transport, - the pathological breakdown of the barrier and - the modification of drugs to increase their entry into the brain. Here is a source of information that is invaluable to specialists concerned with basic research in the neurosciences, with the design of neuropharmacological agents, with the radiological diagnosis of cerebral pathology or with the treatment of cerebral lesions!
Neuroglia by Helmut Kettenmann,Bruce R. Ransom Pdf
Neuroglia is the only comprehensive reference book on the basic biology and function of glial cells. This long-awaited second edition has been completely reorganized and rewritten to include the dramatic advances in this field since the first edition was published ten years ago. The impact of the second edition will be greater than that of the first because the majority of neuroscientists now acknowledge that neuroglia are elemental to most, if not all, brain functions. The second edition covers the entire field of glial research from the basic molecular and cellular principles of these cells to their involvement in neurological diseases including stroke, Alzheimer's disease, and multiple sclerosis. It includes new chapters on transmitter release from exocytosis from glia, glia derived stem cells, glia and synaptic transmission, glia and axon guidance, an entirely new section on mechanisms of glial injury, and several new chapters on the roles of glia in different diseases. The new edition was written with both students and experts in mind. It provides a basic introduction to the entire range of glial topics and detailed information with critical assessment of the research literature. Neuroscience textbooks focus on the properties of neurons, whereas this book fills the information void about the brain's other cells. Neuroglia, Second Edition, is an essential reference source for newcomers, including graduate students, to neuroanatomy, neurochemistry, neurophysiology, and molecular neurobiology. It is also a vital companion for established researchers in these fields as well as clinicians in neurology, neurosurgery, psychiatry, neuropathology, and neuro-oncology.
Barriers and Fluids of the Eye and Brain by Malcolm Beverley Segal Pdf
This volume presents the latest findings regarding the control of the fluid environments of the eye and brain. The book is comprised of papers presented at a symposium honoring the 80th birthday of Professor Hugh Davson. The contributors are previous students of Hugh Davson who are now leading authorities in the fields of the eye and brain. The eye is considered from its many interfaces, including the role of prostaglandins, blood flow in diabetes, and the vitreous body. Other topics discussed include the role of carbonic anhydrase, cerebrospinal fluid and its drainage, and the development of the blood/brain barrier to macromolecules. The book also shows how recent findings about homologous molecules refute earlier studies with foreign tracers, and offers a fascinating glimpse into the future with a description of the latest imaging techniques used in neurological diagnosis.