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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aluminum present as a contaminant in ATP preparations can cause strong inhibition of yeast hexokinase P-II activity at pH 7.0 or below but has little or no inhibitory effect at a pH of 7.5 or greater. The inhibition is reversed by citrate, 3-phosphoglycerate, malate, phosphate, and catecholamines, all of which have previously been described as activators of hexokinase at low pH. We suggest that these agents activate the enzyme only by virtue of their ability to coordinate with aluminum present in the assay system. The presence of aluminum is also responsible for the "negative cooperativity" observed at low pH with respect to Mg . ATP concentration--i.e., the inhibition by aluminum is uncompetitive at low Mg . ATP concentrations but becomes competitive at high Mg . ATP concentrations. The inhibition is thought to be due to formation of a complex of Al . ATP with the enzyme, with a dissociation constant (Ki) of 0.1 microM. Yeast hexokinase P-I is somewhat less sensitive to A1 than is hexokinase P-II, and yeast glucokinase is not detectably affected. The hexokinase in rat brain (type I) shows a pH-dependent inhibition by Al similar to that observed with the yeast hexokinases, whereas the rat muscle (type II) enzyme is less sensitive, suggesting a possible relationship to aluminum encephalopathy in man.
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PMID:Proton-dependent inhibition of yeast and brain hexokinases by aluminum in ATP preparations. 11 25

Experiment studies were performed on rats that were administered mercury chloride sublimate with a special gastric cannule in a single 6 mg dose for four consecutive days. As a result of the investigations some changes in the phosphates and esterases activity were revealed. The diminution of AcP, AIP, ATP-ase and AChE activity as well as in the increase in TPP-ase activity in the neurocytes, and also the appearance on NsE activity in many oligodendrocytes was observed. The fall in ATP-ase activity was, above all, observable in cerebral and cerebellar capillaries, which is, in the authors opinion, a manifestation of enzymatic damage to the blood-brain barrier due to a toxic action of mercuric chloride. In the discussion attention was drawn to differences in the degree of enzymatic activity between a mercuric chloride intoxication and that with mercurous chloride, as well as attempt was made to explain the pathogenetic mechanism of this phenomenon. Furthermore, notice was brought to the fact that in the course of sublimate encephalopathy no changes are observed in BuTJ activity.
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PMID:Phosphatases and esterases activity in the brain following an acute sublimate intoxication. 19 75

A total systems approach was used to study the structural and functional properties of red blood cells in 100 patients suffering from atherosclerotic circulatory encephalopathy, stages I-III: aggregation, deformability, superficial cytoarchitectonics, the content of ATP and 2,3 DPH, transport of univalent cations, and the cholesterol/phospholipid index of membranes. It has been demonstrated that as the atherosclerotic process progresses, the membrane rigidity increases as a result of excessive concentration of cholesterol in the cell, aggregation is enhanced, transport of ions and substances gets disturbed, the processes of glycolysis and synthesis of macroergs get inhibited. All this brings about the derangement of transport function of the cells because of disturbance of the properties of moving in the system of microcirculation.
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PMID:[Structural and functional properties of erythrocytes in patients with arteriosclerotic circulatory encephalopathy]. 166 83

Environmental and occupational exposure to lead still generates concern, and recent studies have focused such concern on the role of body burden of lead during the fetal/neonatal period, especially in the genesis of disturbed central nervous system development. This discussion provides some comparative observations on the neurotoxicity of inorganic and organic lead species. The characteristics acute, predominantly cerebellar encephalopathy associated with neonatal high lead exposure contrasts to the subtle, axo-dendritic disorganization shown to be associated with low-level neonatal inorganic Pb2+ exposure. There is a preferential involvement of the hippocampus in both low-level inorganic Pb2+ and organolead exposure, and the clinical syndromes of irritability, hyperactivity, aggression, and seizures are common features of disturbed hippocampal function. Neurotransmitter system abnormalities have been described with inorganic Pb2+, but recent attention has focused on the abnormalities in glutamate, dopamine and/or gamma-aminobutyric acid (GABA) uptake, efflux, and metabolism. Abnormalities of GABA and glutamate metabolism are also found with the organolead species. While the pathogenesis is still unclear, the interactive role of Pb2+ on mitochondrial energy metabolism, Ca2+ uptake, intracellular Ca2+ homeostasis, and neurotransmitter influx/efflux is considered. Consideration is given to low-dose inorganic Pb2+ and organolead effects on mitochondrial and/or plasmalemmal membranes inducing either Cl-/OH- antiport-linked depolarization, inhibition of intracellular ATP biosynthesis and transduction. and/or abnormalities induced due to the preferential affinity of Pb2+ for intracellular Ca2(+)-cytoplasmic protein, e.g. calmodulin. Testable hypotheses are presented that may provide an understanding of the pathogenesis underlying dystrophic neuronal development under the influence of inorganic or organolead intoxication.
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PMID:Comparative observations on inorganic and organic lead neurotoxicity. 198 34

In a preceding paper, we showed that the exposure to hypoxia after unilateral carotid artery ligation of sucking rat on 7 days of age caused various pathological changes in the ipsilateral forebrain, which had close similarity to human perinatal hypoxic-ischemic encephalopathy. To evaluate the energy metabolism in various regions of the brain during hypoxia after unilateral carotid artery ligation, tissue pH was monitored in the cortex by direct insertion of an electrode. The contents of the lactate, pyruvate, ADP and ATP were also measured during hypoxia. The tissue pH in the cortex of ligated side declined rapidly after initiation of hypoxia as compared to non-ligated side. The contents of pyruvate and ADP showed no particular changes through various regions. Only in the cortex and hippocampus of ligated side, ATP was decreased, and elevation of lactate was more salient than in non-ligated side. In the striatum and thalamus, only elevation of lactate was indicated. However, the levels of lactate, pyruvate, ADP and ATP disclosed no significant difference between the ligated side and non-ligated side, although neuropathological changes were observed only in their ligated side. These results suggest that pathogenesis of the cerebral damage caused by hypoxic-ischemic condition may be different between the cerebral cortex and subcortical structures.
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PMID:[Experimental study on pathogenesis of neonatal hypoxic-ischemic encephalopathy. II. Energy metabolism in the brain]. 222 83

Systemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high-energy phosphates in the central nervous system of 10 patients with SLE and 10 age-matched normal controls. 31P NMR spectroscopy was performed on a 1.5-Tesla unit equipped with a dual-tuned 1H-31P surface coil and a software-directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean +/- SD 0.81 +/- 0.11 versus 0.91 +/- 0.05; P less than 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high-energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.
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PMID:Depletion of high-energy phosphates in the central nervous system of patients with systemic lupus erythematosus, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy. 236 38

An investigation of the mechanism of development of hepatic encephalopathy induced by CCl4 was performed in rats. CCl4 (1.0 ml/kg three times per week for over 10 weeks) caused hepatic encephalopathy in 80% of the treated rats. Accompanying the hepatic encephalopathy were hematemesis, abdominal dropsy, and hyperammonemia, conditions observed in hepatic coma patients. The blood ammonia levels were tremendously increased in only those rats with hepatic encephalopathy. Hepatic activities of carbamylphosphate synthetase (CPS) and argininosuccinate synthetase (ASS), important enzymes of the urea cycle, were significantly inhibited by CCl4. However, the causality between the inhibition of CPS or ASS activity and the increase in blood ammonia levels was not observed. On the other hand, the content of ATP, which is a substrate of CPS and ASS, was decreased by 60% in liver of rats with hepatic encephalopathy. The activity of Mg2+-ATPase which can decompose hepatic ATP was increased by 60 and 300% in mitochondria and microsomes, respectively, of livers of rats with CCl4-induced encephalopathy. There was a good correlation between the decreased hepatic ATP content and the increased mitochondrial Mg2+-ATPase activity. Furthermore, there was also a good correlation between the increase in blood ammonia levels and the increase in Mg2+-ATPase activity in microsomes. These findings suggest that hyperammonemia, which was produced by the decrease in hepatic content and by the inhibition of CPS and ASS, may play an important role in induction of hepatic encephalopathy.
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PMID:Blood ammonia levels and hepatic encephalopathy induced by CCl4 in rats. 296 38

The Alzheimer type II astrocyte change is the distinctive morphologic alteration in brain of humans and experimental animals succumbing to hepatic encephalopathy (HE). Whether this change is a primary event in the pathogenesis of HE or whether it is secondary to injury of some other component(s) of the CNS has not been clarified. Studies in a rat model of HE have revealed early reactive changes in astrocytes characterized by cytoplasmic hypertrophy. During the later phases, degenerative changes ensue corresponding to the Alzheimer type II change observed by light microscopy. In view of the role of astrocytes in ammonia detoxification and the importance of ammonia in the pathogenesis of HE, we have suggested that the initial astrocytic changes are the morphological correlates of ammonia detoxification. We have speculated that the later degenerative alterations could lead to failure by astrocytes to carry out key functions (e.g., neurotransmitter uptake, ion regulation, and the like) and contribute the development of the encephalopathy. Recently, the potential involvement of astrocytes in HE has been further investigated, using primary astrocyte cultures. Exposure of cultures to ammonia at clinically relevant concentrations has shown morphologic changes closely resembling those observed in experimental HE in vivo. These deleterious effects can partly be prevented by raising cyclic AMP levels in cells. Other potential toxins (octanoic acid, phenol) have shown pathologic changes as well. Although some alterations were common to all three, they each possessed distinctive pathological effects. A synergistic interaction has also been demonstrated with these toxins. Functional studies of ammonia-treated astrocytes have shown the following: With low doses or short-term exposure, the uptakes of K+, glutamate, and GABA remained unchanged or slightly increased, whereas with higher doses or longer treatment, those activities diminished. A fall in ATP values occurred with prolonged ammonia treatment. Preliminary findings have shown no significant derangements in the beta-adrenergic receptor, except for a slight decrease in receptor affinity. However, cyclic AMP production was diminished following stimulation with isoproterenol. A slight rise in the number of benzodiazepine receptors was found. These studies indicate that profound changes occur in astrocytes following exposure to ammonia and other putative toxins. It is proposed that toxins and factors involved in the precipitation of HE do so by affecting astroglial properties. Derangements in such properties may lead to glial dysfunction (primary gliopathy), resulting in an encephalopathic state.
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PMID:The role of astrocytes in hepatic encephalopathy. 330 80

Thiamine-deficient encephalopathy is characterized by morphologic lesions in the brainstem and less extensively in the cerebellum, but the early neurologic signs reverse rapidly and fully with thiamine, indicating a metabolic disorder. The suggested causal mechanisms of the encephalopathy involve two thiamine-dependent enzymes: (a) impairment of pyruvate decarboxylase activity with decreased cerebral energy (ATP) synthesis, and (b) reduction of transketolase activity with possible impairment of the hexose monophosphate shunt and subsequent decrease in NADPH formation. The latter may be important in maintaining glutathione in a reduced form (GSH), which apparently functions by keeping enzymes in a reduced (active) conformation. To examine some of these postulated mechanisms, in this study we measured pyruvate decarboxylase and transketolase activity, lactate, ATP and GSH levels in the cerebral cortex, cerebellum, and brainstem, and thiamine concentration in whole brain of rats with diet-induced low thiamine encephalopathy. Pair-fed and normally fed asymptomatic control animals were similarly investigated. To assess the functional importance of some of our results, we repeated the studies in rats, immediately (16-36 hr) after reversal of the neurological signs with thiamine administration. THE DATA OBTAINED LED TO THE FOLLOWING CONCLUSIONS: (a) Brain contains a substantial reserve of thiamine in that thiamine level has to fall to below 20% of normal before the onset of overt encephalopathy and an increase in brain thiamine to only 26% of normal results in rapid reversal of neurologic signs. (b) Both cerebral transketolase and pyruvate decarboxylase activities are impaired in low thiamine encephalopathy and the abnormality in the pyruvate decarboxylase is reflected in a rise in brain lactate. These biochemical abnormalities occur primarily in the brainstem and cerebellum, the sites of the morphologic changes. (c) Although the fall in cerebral transketolase is about twofold greater than that of pyruvate decarboxylase activity during encephalopathy, both enzymes rise on reversal of neurologic signs and the degree of the transketolase rise is slight. Accordingly, this study cannot ascertain the relative functional importance of these two pathways in the induction of the encephalopathy. The data suggest, however, that the depression of transketolase is not functionally important per se, but may only be an index of some other critical aspect of the hexose monophosphate shunt. (d) The normal cerebral ATP concentration and small GSH fall during encephalopathy, with little GSH rise on reversal of neurologic signs, suggest that a depletion of neither substance is instrumental in inducing thiamine-deficient encephalopathy.
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PMID:Encephalopathy of thiamine deficieny: studies of intracerebral mechanisms. 567 22

Ammonia intoxication decreases the hyperpolarizing action of postsynaptic inhibition. This study examines the metabolic state of the spinal cord during this effect of ammonia intoxication on spinal motoneurons. ATP, ADP, AMP, the adenylate energy charge, glucose, PCr, pyruvate, alpha-ketoglutarate and glutamate were unchanged during the effect of ammonia on the hyperpolarizing action of postsynaptic inhibition. NH4+, glutamine and lactate were increased. Ammonia intoxication affected postsynaptic inhibition without changes of the resting membrane potential, the neuron input resistance, the action potential and EPSPs. The encephalopathy caused by ammonia intoxication is known to occur without an alteration of the tissue energy state. The effect of ammonia intoxication on postsynaptic inhibition can be considered as a cause of the encephalopathy because postsynaptic inhibition is altered without a change of the tissue energy state, the resting membrane potential, the whole neuron resistance, the action potential and EPSPs.
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PMID:Ammonia, postsynaptic inhibition and CNS-energy state. 632 74


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