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

Inorganic lead, added to the diet of suckling rat in high doses, produces an encephalopathy similar to that seen in the immature human. Pathologic changes of edema and hemorrhage are seen earliest and are most prominent in the cerebellum. In this study, we measured respiration in cerebral hemisphere and cerebellar mitochondria isolated from led-fed and age-matched normal rat pups. Lactating mothers were begun on ad libitum feedins containing 4% lead carbonate when their pups were 2 weeks old. Mitochondria were isolated by differential centrifugation. Oxygen consumption was measured polarographically, NAD-linked respiration was measured with oxidation of the substrate pair, glutamate and malate. Cytochrome oxidase (cytochrome c oxidase, EC. 1.9.3.1) activity was measured in the presence of tetramethyl-p-phenylenediamine dihydrochloride (TMPD) and ascorbate. Within 2 days of starting lead feedings, rat pups showed a significant loss in body weight (P less than 0.02) and, after 1 week, a significant loss in cerebral hemisphere wet weight (P less than 0.01) compared with controls. Overt encephalopathy appeared in pups from two of nine litters receiving lead feedings for 1 week and in half of the litters after 2 weeks of feedings. None of the lead-fed mothers developed encephalopathic signs. With oxidation of the NAD-linked substrate pair, there was a progressive decrease, relative to controls, in ADP/O ratios in both cerebellar and cerebral mitochondria from lead-fed animals. After 2 weeks these differences were significant in mitochondria from both regions (cerebellum, P less than 0.02; cerebrum, P less than 0.005). Respiratory control ratios were significantly lower in cerebellar mitochondria from lead-fed rats within 2 days of beginning feedings (P less than 0.02) and in mitochondria from both regions after 2 weeks of lead feedings (cerebellum, P less than 0.01; cerebrum, P less than 0.05). The decrease in control ratios in cerebellar mitochondria from animals receivint lead feedings for 1 week or less was due to a small decrease in state 3 respiration and a large, but inconsistent, increase in state 4 respiration. The decrease in control ratios in both cerebellar and cerebral hemisphere mitochondria after 2 weeks of lead feedings was due to a marked inhibition of state 3 respiration, relative to controls (cerebellum, P less than 0.01; cerebral hemisphers, P less than 0.05). In cerebellar mitochondria from lead-fed animals, cytochrome oxidase activity showed similar changes compared with controls: a highly significant (P less than 0.001) increase within 2 days of beginning feedings and a significant (P less than 0.01) decrease after 2 weeks of feedings.
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PMID:Early effects of inorganic lead on immature rat brain mitochondrial respiration. 17 53

We report a patient with fulminant Lassa fever who responded dramatically to a 2.5-litre exchange transfusion of whole blood. On admission he was semicomatose with facial oedema and oral haemorrhage; his platelets showed markedly depressed aggregation to ADP; and his plasma inhibited the aggregation responses of normal platelets in vitro. Exchange transfusion resulted in rapid clinical improvement, recovery of platelet function, and disappearance of platelet-inhibitory activity in plasma. The patient died 2 weeks later from an acute encephalopathy. His initial response was sufficiently impressive to suggest that further evaluation of this therapeutic approach is justified in selected patients with overwhelming Lassa virus infection.
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PMID:Exchange transfusion of a patient with fulminant Lassa fever. 204 53

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

Primary cultures of astrocytes were used to investigate the effects of glucose deprivation on plasma membrane potential, on the respiration and on the energy status of these cells. Plasma membrane potential, as monitored with a cyanine dye, 3,3'-diethylthiadicarbocyanine, hyperpolarized by about 100% when glucose was added to substrate-deprived cells. The effect of glucose was prevented by iodoacetate or ouabain. In the absence of glucose, cellular adenosine triphosphate/adenosine diphosphate ratio was extensively reduced and pyruvate was unable either to restore energy status or to hyperpolarize the plasma membrane of astrocytes, although it was the preferential substrate for mitochondria within the cells. Glucose deprivation and inhibition of glycolysis or respiration in the presence of glucose caused dramatic decrease in transmembrane potassium ion and L-glutamate gradients. The gradients were not restored in the presence of pyruvate. Thus, aerobic glycolysis, rather than oxidation of pyruvate, is required to maintain maximal plasma membrane potential, adenosine triphosphate/adenosine diphosphate ratios as well as K+ and L-glutamate gradients. This evidence, together with the unresponsiveness of astrocyte respiration to ouabain, indicates a functional dissociation between energy dissipation at the plasma membrane and mitochondrial synthesis of adenosine triphosphate. The results are discussed with regard to the vulnerability of glia at low levels of blood glucose and the contribution of glial dysfunction to development of hypoglycaemic encephalopathy.
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PMID:Glucose deprivation depolarizes plasma membrane of cultured astrocytes and collapses transmembrane potassium and glutamate gradients. 290 93

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) greater than 150 IU/L or viremia of greater than 10(3.6) tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST less than 150 IU/L or viremia, less than 10(3.6)TCID50/ml), (P less than 0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P less than 0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P less than 0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P less than 0.0035 in response to ADP and P = 0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P = 0.0013 for ADP and P less than 0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematologic dysfunction in Lassa fever. 318 37

It has been suggested that pertussis toxin (Ptx) is involved in the pathogenesis of the adverse neurologic reactions that can occur in infants and children after pertussis immunization. One group of investigators has recently reported that a clinical syndrome with pathological features very similar to post-pertussis vaccination encephalopathy can be induced in specific strains of mice after their immunization with bovine serum albumin (BSA) and Ptx. The aim of this investigation was to further characterize the immunologic mechanisms operative in this murine model. Studies were undertaken to determine whether the role played by Ptx in this condition required the A-protomer of the toxin to enter a cell and ADP-ribosylate a nucleotide binding protein (a Class I activity) or was dependent upon the binding of the B-oligomer of the toxin to the surface of target cells (a Class II activity). The results of our experiments have established that the disease induced by coimmunizing mice with Ptx and BSA is due to an immediate type hypersensitivity reaction rather than an encephalopathy and that the mechanism of action of Ptx in this system seems to be dependent upon a Class II activity of the toxin and independent of its ADP-ribosyl transferase activity.
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PMID:Murine responses to immunization with pertussis toxin and bovine serum albumin: I. Mortality observed after bovine albumin challenge is due to an anaphylactic reaction. 330 58

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

Aluminum accumulates on DNA containing nuclear structures in several human degenerative brain diseases and following the direct injection of aluminum into the brain of certain experimental animals. The enzyme poly(ADP-ribose) synthetase is activated following DNA damage. Aluminum added to nuclei, in vitro, at concentrations approaching that necessary to induce a progressive encephalopathy in animals, reduces poly(ADP-ribose) formation to 75% of control. Nuclei extracted at various stages of the aluminum encephalopathy exhibit a reduction in ADP-ribosylation to 50% of control nuclei. Altered ADP-ribosylation may be an important nuclear consequence of aluminum toxicity in both the experimental models and in degenerative human brain disease.
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PMID:Aluminum inhibition of ADP-ribosylation in vivo and in vitro. 642 19

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder of unknown pathogenesis characterized by migraine and transitory hemiplegic attacks. We describe a kindred fulfilling the diagnostic criteria for FHM in which: (1) brain phosphorus magnetic resonance spectroscopy (31P-MRS) showed a reduced phosphocreatine content accompanied by high [ADP], high percentage of V/Vmax of ATP biosynthesis and decreased phosphorylation potential; (2) muscle 31P-MRS showed a reduced rate of phosphocreatine recovery after exercise; (3) blood lactate was increased after effort; (4) muscle biopsy showed, in one patient, rare ragged red fibers succinate-dehydrogenase positive and cytochrome c oxidase negative; (5) genetic analysis of muscle mitochondrial DNA did not show any of the two point mutations in the tRNA(Leu(UUR)) associated with the MELAS syndrome (Mitochondrial myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes). The defective energy metabolism of brain and muscle found in this pedigree suggests a multisystemic disorder of mitochondrial function in this FHM pedigree.
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PMID:Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. 760 38


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