Nervous system metabolism

Chanimov M, Cohen ML, Grinspun Y et al. (1997) Neurotoxicity after spinal anaesthesia induced by serial intrathecal injections of magnesium sulphate. Anaesthesia 52 223-228 Cole DJ, Lin DM, Drummond JC, Shapiro HM (1990) Spinal tetracaine decreases central nervous system metabolisms during somatosensory stimulation in the rat. Can J Anesth 37 231-237... 

Recently, Li etal,162 used ABPP competitive profiling to screen libraries of carbamate compounds to identify specific inhibitors for uncharacterized serine hydrolases. The carbamate reactive group reacted irreversibly with the active site serine, which, in turn, blocked subsequent labeling with a fluorescent FP probe. The carbamates were decorated with various side chains in order to find the optimal composition for dedicated target binding. Utilizing this method, a potent and selective inhibitor for a//3-hydrolase domain 6, which may play important functions in nervous system metabolism or signaling, was discovered. 

The most common PDC genetic defects are in the gene forthe a subunit of Ei. The E, a-gene is X-linked. Because of its importance in central nervous system metabolism, pyruvate dehydrogenase deficiency is a problem in both males and females, even if the female is a carrier. For this reason, it is classified as an X-linked dominant disorder. 

HUMAN TOXICITY DATA oral-man TDLo 700mg/kg oral-man TDLo 50mg/kg toxic effect gastrointestinal tract oral-man TDLo 1430pg/kg toxic effect central nervous system oral-human LDLo 1400 mg/kg oral-woman TDLo 256g/kg/12W toxic effect central nervous system, endocrine system oral-woman TDLo 41g/kg (41 W pregnancy) toxic effect reproductive effects intrauterine-woman TDLo 200mg/kg (5D pre) toxic effect reproductive effects dna inhibition-human lymphocyte 220 mmol/L subcutaneous-infant LDLo 19,440 mg/kg toxic effect central nervous system, metabolic effects. 

Magnesium and the Peripheral (Extradural) Nervous System Metabolism, Neurophysiological Functions, and Clinical Disorders Jerry G. Chutkow... 

An interesting set of central nervous system properties has also been discovered and studied (Table VI-10). The work devoted to piscaine must be emphasized besides finding hypnotic properties of 2-amino-4-phenyl-thiazole on fish, the authors studied the structure of the metabolite, as well as the localization of the (radio labeled) metabolic product in various organs. Recently, thiazol-4-yl methoxyamine was shown to inhibit the development of morphine tolerance (1607). 5-Aminothiazole derivatives such as 419a were proposed as cardiovascular agents (1608, 1610). Substitution of the 5-aminothiazole radical on the cephalophosphorin structure gives a series of antibacterial products (1609). 

Metabolic Functions. Manganese is essential for normal body stmcture, reproduction, normal functioning of the central nervous system, and activation of numerous enzymes (126). Synthesis of the mucopolysaccharide chondroitin sulfate involves a series of reactions where manganese is required in at least five steps (127). These reactions are responsible for formation of polysaccharides and linkage between the polysaccharide and proteins that form... 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

Adrenaline (epinephrine) is a catecholamine, which is released as a neurotransmitter from neurons in the central nervous system and as a hormone from chromaffin cells of the adrenal gland. Adrenaline is required for increased metabolic and cardiovascular demand during stress. Its cellular actions are mediated via plasma membrane bound G-protein-coupled receptors. 

The adrenergic system is an essential regulator that increases cardiovascular and metabolic capacity during situations ofstress, exercise, and disease. Nerve cells in the central and peripheral nervous system synthesize and secrete the neurotransmitters noradrenaline and adrenaline. In the peripheral nervous system, noradrenaline and adrenaline are released from two different sites noradrenaline is the principal neurotransmitter of sympathetic neurons that innervate many organs and tissues. In contrast, adrenaline, and to a lesser degree noradrenaline, is produced and secreted from the adrenal gland into the circulation (Fig. 1). Thus, the actions of noradrenaline are mostly restricted to the sites of release from sympathetic nerves, whereas adrenaline acts as a hormone to stimulate many different cells via the blood stream. 

Glial cells are cells within the central or peripheral nervous system which are not immediately involved in information processing. Glial cells play an mportant role in the metabolic homeostasis of brain tissue and in nervous system development. 

In conclusion, the discovery of incretins has now come to an end in terms of therapeutic strategy of metabolic diseases since new medicines will be put on the market these coming years. However, a lot more needs to be done with regard to the physiological role of the hormones. Whereas the major filed of investigation for GLP-1 now relates to the effect of the peptide on the central nervous system and on (3-cell proliferation, for GIP it remains to understand its role in the numerous tissues where the corresponding receptor is expressed. 

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

Vitamin B6-coenzyme is involved in a variety of reactions, e.g., in the immune system, gluconeogenesis, erythrocyte fimction, niacin formation, nervous system, lipid metabolism, and in hormone modulation/gene expression [1, 2]. 

Diseases affecting skeletal muscle are not always primary diseases of muscle, and it is necessary first to determine whether a particular disorder is a primary disease of muscle, is neurogenic in origin, is an inflammatory disorder, or results from vascular insufficiency. A primary disease of muscle is one in which the skeletal muscle fibers are the primary target of the disease. Neurogenic disorders are those in which weakness, atrophy, or abnormal activity arises as a result of pathological processes in the peripheral or central nervous system. Inflammatory disorders may result in T-cell mediated muscle damage and are often associated with viral infections. Vascular insufficiency as a result of occlusion in any part of the muscle vasculature can cause severe disorders of muscle, especially in terms of pain, metabolic insufficiency, and weakness. 

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