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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical and behavioral effects of the anticonvulsant amino-oxyacetic acid (AOAA) have been studied in a model of focal penicillin seizures in rats. At 20 mg/Kg AOAA treatment results in a progressive 11 fold increase in GABA levels in cortex over three hours. There is a decrease in aspartate, ketoglutarate, alanine and glutamine, and an initial decrease followed by an increase in pyruvate and glutamate. These results reflect a functional inhibition of several B-6 dependent aminotransferase enzymes. When rats are pretreated 30 min before the onset of focal penicillin seizures there is a 60% reduction in the number of discharges and a 34% reduction in seizure duration. Pretreatment beyond 75 min results in progressively less anticonvulsant effect, such that seizures eventually become more severe than control. There is an increase in the number and duration of discharges, seizure spikes become complex, and tonic-clonic events develop. Penicillin seizures do not cause a change in levels of GABA, but result in a decrease in glutamate within the focus. AOAA pretreatment initially prevents this decrease in glutamate but later accentuates it. The biochemical effects of AOAA are complex, but biphasic anticonvulsant properties coincide in time with a change in the balance of excitatory and inhibitory amino acids in the seizure focus.
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PMID:Effect of amino-oxyacetic acid (AOAA) on focal penicillin seizures. 10 8

A Canadian Indian family is described in which three of the children were mentally retarded, and had seizures and other neurological abnormalities. They had chronic metabolic acidosis associated with elevated blood levels of lactate, pyruvate, and alanine. Two of the children excreted large amounts of pyruvic and alpha-ketoglutaric acids in the urine and had elevated plasma levels of glutamic acid and proline. Hypoglycemia occurred with fasting in two of the children. Treatment with pharmacological doses of thiamine, lipoic acid, biotin, riboflavin, and various dietary regimes was without effect. One child died at 3 1/2 months and another at 4 1/2 months; the third is still alive at 23 months of age. Enzyme assays revealed a low level of activity of both the pyruvate and alpha-ketoglutarate dehydrogenase complexes in cultured fibroblasts of one of the sibs. These patients appeared to have partial defects in the oxidation of pyruvate, as well as of alpha-ketoglutarate within the tricarboxylic acid cycle.
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PMID:Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. 18 26

A 10 month old female infant was evaluated for severe lactic acidosis. Clinically she was well nourished and had a substantial amount of adipose tissue despite recurrent episodes of acidosis. Her psychomotor development was retarded, her movements were dystonic and generalized seizures punctuated her course. Metabolic abnormalities included elevated blood concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alanine, proline and glycine, decreased blood concentrations of glutamine, aspartate, valine and citrate, and intermittent elevations of serum cholesterol. A trial on a high-fat diet worsened the clinical condition and intensified the ketoacidosis and hyperalaninemia. Analysis of hepatic tissue obtained by open biopsy revealed increased concentrations of lactate, alanine, acetyl-CoA and other short-chain acyl-CoA esters, and decreased concentrations of oxaloacetate, citrate, alpha-ketoglutarate, malate and aspartate. The blood and tissue metabolic perturbations reflected a deficiency of hepatic pyruvate carboxylase. The apparent Km of hepatic citrate synthase for oxaloacetate was 4.6 micrometer. Calculated tissue oxaloacetate concentrations were 0.50--0.84 micrometer suggesting that tricarboxylic acid cycle activity was severely limited by the decreased availability of this substrate. An iv glucose tolerance test resulted in the paradoxical synthesis of ketone bodies. This observation, coupled with the intermittent hypercholesterolemia and the increased tissue acetyl-CoA concentrations, suggests that pyruvate carboxylase is important in modulating the fractional distribution of intracellular acetyl-CoA between the tricarboxylic acid cycle, the beta-hydroxy-beta-methyl-glutaryl-CoA cycle (and the synthesis of cholesterol and ketone bodies), and fatty acid synthesis. Treatment in future cases might be directed toward increasing tissue concentrations of oxaloacetate.
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PMID:The clinical and biochemical implications of pyruvate carboxylase deficiency. 41 60

Progressive cerebral ischemia was induced by blood pressure (BP) reduction in rats during status epilepticus, and the sequence of cerebral functional (EEG, extracellular K+ activity) and metabolic (levels of high energy phosphates, glucose, glucose-6-phosphate, lactate, pyruvate, alpha-ketoglutarate) changes were determined. Very moderate reductions of BP were accompanied by tissue lactate accumulation and a decrease of the rate of re-uptake of K+ extruded during discharges. These changes were pronounced at BP about 50 mm Hg, when also the energy state showed some deterioration, and the EEG activity changed from one of bursts and suppressions into single spikes. At BP about 30 mm Hg EEG activity was abolished, but not until a slightly lower BP level was there a severe energy depletion and a massive K+ release, indicating generalized membrane depolarization. The results show an increased susceptibility to ischemia during seizures with changes of membrane pump function, and energy metabolism appearing at moderate reductions of BP. Concomitant decrease of seizure activity delayed to some extent the development of massive energy failure and membrane depolarization.
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PMID:Effects of reduced cerebral blood flow upon EEG pattern, cerebral extracellular potassium, and energy metabolism in the rat cortex during bicuculline-induced seizures. 49 17

Levels of pyruvate and alpha-ketoglutarate in the cerebrospinal fluid (CSF) of 26 children, aged 4 months to 5 1/2 years, with febrile seizures and of 19 children, aged 4 months to 14 years, with the diagnosis of epilepsy were not different from values seen in 119 "normal" children 8 days to 14 years of age. The CSF samples from 24 adults, 24 to 81 years of age, suspected of having a herniated disk were also examined. In the pediatric age group, the data showed a highly significant downward trend of CSF and plasma alpha-ketoglutarate values with age; pyruvate values did not change. A correlation of the values of the two keto acids in the blood and CSF of 42 other children without apparent neurologic disease was also made. Findings in a child with thiamine deficiency suggest that CSF alpha-ketoglutarate may be a more sensitive indicator of deficiency than plasma alpha-ketoglutarate or pyruvate. Measurements of these keto acids in plasma and CSF may be diagnostically useful in a variety of metabolic disorders. Findings in 155 children from birth (20 minutes) to 17 years of age without neurologic disease are submitted as a standard of reference.
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PMID:Fluorometric determination of pyruvate and alpha-ketoglutarate in cerebrospinal fluid and plasma of infants and children. A simple test that screen for metabolic disorders. 98 54

The effects of DL-penicillamine (DL-PeA), hydrazine and toxopyrimidine (TXP, 2-methyl-6-amino-5-hydroxymethylpyrimidine) on gamma-aminobutyric acid (GABA) metabolism in mouse brain were studied. All these compounds inhibited the activity of glutamate decarboxylase [EC 4.1.1.15] (GAD) and slightly inhibited that of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 2.6.1.19] (GABA-T). In contrast, very different effects were observed on GABA levels; hydrazine caused a marked increase, DL-PeA had no effect, and TXP caused a slight decrease in the content of the amino acid. These results could be described by an equation which related the excitable state to changes in the flux of the GABA bypass. Since the values obtained from the equation clearly reflect the seizure activity, it is suggested that the decreased GABA flux might be a cause of convulsions induced by these drugs.
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PMID:A correlation between changes in gamma-aminobutyric acid metabolism and seizures induced by antivitamin B6. 100 83

We investigated both blood and cerebrospinal fluid (CSF) lactate and pyruvate levels in seven girls with the Rett syndrome (RS) and evaluated the relationship between CSF lactate and pyruvate levels and the clinical manifestations, particularly seizures, anticonvulsant medication, and breathing dysfunction including breath holding, apnea and hyperventilation. Elevated lactate and pyruvate levels in CSF with normal serum lactate were found in two RS patients. Elevated CSF lactate correlated significantly with the clinical occurrence of hyperventilation (P0 = 0.048, Fisher exact probability). We measured native and dichloroacetate (DCA)-activated pyruvate dehydrogenase (PDH) complex activities in two patients (#1 and 2) using cultured lymphoblastoid cell lines which were transformed by EB virus and the results were normal. We also analyzed CSF citric acid intermediates from 7 RS patients including citric acid, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate. These concentrations were not significantly different from those control patients (N = 21). An elevated lactate level may be a clue to clarify the etiology of RS.
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PMID:The Rett syndrome and CSF lactic acid patterns. 159 May 31

Biochemical and pharmacological effects of gamma-vinyl GABA (Vigabatrin, GVG), and irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- and dose-dependent elevation of the GABA, phenylalanine and lysine contents of cortical tissue and simultaneously decreased glutamate, aspartate and alanine levels. In addition, GVG caused a biphasic change in glutamine concentrations (a decline 1-4 hours after administration, followed 20 hours later by an increase). Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column. The level of this novel chemical entity was greatly increased by GVG 20 hours after injection of the drug. At all tested intervals between 1 and 60 hours after injection, GVG was ineffective against maximal electroshock. The GABA-T inhibitor dose-dependently protected mice against isoniazid-induced seizures, simultaneously causing an increase in brain GABA concentrations. However, this apparent correlation applied only until 4 hours after treatment. To better define the anticonvulsant profile of GVG, groups of mice were treated, 1, 2, 4, and 24 hours prior to challenge with convulsant doses of strychnine, pentetrazole (PTZ), and picrotoxin, and brain amino acid levels, including brain concentrations of GVG, were measured. In all instances, the time dependency of the anticonvulsant effects of GVG and of increases in brain GABA levels differed. Amino acid concentrations in animals treated only with GVG were similar to those in animals given GVG and a chemical convulsant. GVG showed no selectivity for seizures produced by impairment of GABA-ergic neurotransmission. Although GVG is an effective GABA-T inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts with other neurotransmitter systems as well.
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PMID:Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. 341 34

One thousand one hundred and seventy-five mentally retarded patients in an institution (733 males and 442 females) were screened for urinary excretion of 2-oxoacids using a quantitative gas chromatographic method. On follow-up, in 10 out of 31 male patients with excretion of greater than or equal to 50 mmoles 2-oxoglutaric acid per mole creatinine, a previously unrecognized bacteriuria was considered the cause of hyper-2-oxoglutaric aciduria. Of the remaining 21, nine had elevated blood citric acid, and four had borderline elevations of blood pyruvic and/or 2-oxoglutaric acid. In the 11 males with persistent hyper-2-oxoglutaric aciduria an increased incidence of seizure disorders and cerebral palsy relative to the total patient population was found. Hyper-2-oxoglutaric aciduria with concomitant abnormalities of blood metabolites is thought to represent a heterogeneous group of mild inborn errors of energy metabolism which may be compatible with survival at least into young adulthood, but not with normal development of mental and neurological functions.
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PMID:Hyper-2-oxoglutaric aciduria in long-term mental handicap. 378 60

Shortly after birth, a newborn girl developed anorexia, hypotonia, apneic attacks and seizures. After 61 h the child died in coma. Biochemically, a highly elevated blood ammonia level was found together with an increased plasma level of the amino acids mainly involved in ammonia detoxication. Enzyme studies in post-mortem liver tissue material revealed a deficiency of carbamoyl-phosphate synthetase (0.9% of the mean value in controls) in combination with an intermediate activity of L-ornithine: 2-oxoglutarate aminotransferase (40% of the mean value in controls).
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PMID:A lethal neonatal variant of carbamoyl-phosphate synthetase deficiency in combination with an intermediate activity of L-ornithine: 2-oxoglutarate amino-transferase. 685 Dec 28


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