Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance. After intravenous infusion of the keto analogues of valine, leucine, isoleucine, methionine and phenylalanine, the corresponding plasma amino acids, including alloisoleucine and tyrosine, rose sharply. Twenty-four hours later, fasting plasma ammonia had fallen from the preinfusion value of 0.050 to 0.028 mM. Protein intake was kept at 0.5 g per kilogram for two weeks. Addition of keto acids by mouth reduced plasma ammonia and alanine to normal or near normal levels. Seizures and episodes of vomiting and lethargy decreased in frequency. Urinary nitrogen decreased, suggesting that nitrogen balance improved. These data indicate that keto acids may be useful in the treatment of congenital hyperammonemia.
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PMID:Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. 16 4

Single injections of 120 micrograms of methionine-enkephalin were made into various midbrain and forebrain structures in the rat. Analgesia was observed after injections into or near the ventral, caudal midbrain periaqueductal gray matter. Seizures and other pathological electroencephalogram (EEG) changes were seen with injections into or near the forebrain dorsomedial nucleus of the thalamus. No animals with midbrain injection sites showed EEG changes, and none with forebrain injection sites were analgesic. These data, taken together with other lines of evidence, suggest that enkephalin-induced analgesia and enkephalin-induced seizures are mediated by opiate receptors that are located in different brain areas and that are pharmacologically different.
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PMID:Different brain areas mediate the analgesic and epileptic properties of enkephalin. 20 98

Morphologically similar epileptic seizures were recorded from the cortex of rats after injections into the lateral ventricle of 100 microgram of leucine-enkephalin, methionine-enkephalin, and morphine. Seizures were either greatly attenuated or blocked completely by prior systemic administration of naloxone (10 mg/kg). These findings suggest that such seizures result from an interaction of these compounds with opiate receptors in the brain. The epileptogenic potency of the enkephalins was illustrated by the observation that seizures and other pathological manifestations could still be elicited by doses as low as 10 microgram. Leucine-enkephalin was seen to have greater epiliptic potency than methionine-enkephalin. At doses of 1 microgram both enkephalins typically evoked cortical spindles resembling those seen in drowsy animals. Enkephalin-induced analgesia was seen in only one animal at the 100 microgram dose. Results obtained with repeated injections of morphine suggest that the epileptogenic effect of opiates may be subject to either tolerance or potentiation, depending on the prior occurrence of seizures. A synthesis of the present findings with several other lines of evidence suggests both that endogenous enkephalins play some role in normal mechanisms of reward, and that, when regulatory processes are disturbed, they may contribute as well to the elaboration of certain epileptic phenomena.
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PMID:Epileptic properties of leucine- and methionine-enkephalin: comparison with morphine and reversibility by naloxone. 20 15

Homocystinuria with elevated plasma homocysteine and methionine levels is the result of deficient activity of cystathionine synthetase, the enzyme catalyzing conversion of homocysteine to cystathionine. It is inherited as an autosomal recessive trait with a worldwide distribution. The major clinical manifestations result from the elevated plasma homocysteine level. The excitotoxic effect of homocysteic acid accounts for mental retardation and seizures. Interference with collagen cross-linking by sulfhydryl groups of homocysteine causes ectopia lentis and skeletal deformities. Sulfation factor-like effects contribute to disruption of vascular endothelium, which is followed by platelet thrombosis and widespread arterial and venous occlusions. Low methionine homocystinuria, with deficient remethylation of homocysteine, results from deranged vitamin B(12) metabolism and from deficient 5,10-methylene-tetrahydrofolate reductase. Administration of azaribine produces homocystinuria by mechanism not yet elucidated.
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PMID:Homocystinuria: pathogenetic mechanisms. 32 77

An ultrastructural study of cerebral cortex was performed in rats during the preictal period following the administration of the convulsant methionine sulfoximine (MSO). The morphologic changes were restricted to astrocytes and consisted of cytoplasmic enlargement, mitochondrial and rough endoplasmic reticulum proliferation, accumulation of glycogen, development of cisternal and saccular smooth endoplasmic reticulum, nuclear chromatin clumping, and hydropic degenerative changes. These findings resemble those seen in experimental ammonia encephalopathy, suggesting an important role of ammonia in the evolution of these morphologic changes. The findings, moreover, suggest that the primary effect of MSO is on astrocytes and that abnormalities in astrocytes may play a role in the development of MSO-induced seizures.
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PMID:Ultrastructural study of methionine sulfoximine-induced Alzheimer type II astrocytosis. 55 86

The ultrastructure of the rat cerebellar cortex and the activity of succinic dehydrogenase were examined during methionine sulphoximine (MSO)-provoked convulsions. The animals were killed 3, 6 and 12 hours after the injection of 600 mg/kg of MSO. Convulsions appeared 4--5 hours, status epilepticus developed 8-9 hours after the injection. Progressive ischaemic changes of Purkinje cells could be observed, with condensation of the nucleus and a density of the cytoplasmic matrix. The cisternae of the Golgi complex and endoplasmic reticulum showed some degree of dilation. The basis of Purkinje cells was surrounded by distorted axons and terminals that had lost in most cases the synaptic vesicles, and by clear spaces due to the swollen glial processes. Three to six hours after MSO injection, succinic dehydrogenase activity increased in the mitochondria of Purkinje cells. After the appearance of seizures the enzyme activity decreased. Twelve hours after the injection the enzyme activity recovered to a certain extent.
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PMID:Ultrastructural changes in the rat cerebellar cortex during methionine sulphoximine convulsions. 74 16

For purposes of carrying out structure-activity studies on a series of pure R and S enantiomorphs of various para-substituted N-acetyl-alpha-amino-N-phenylglutarimides, we synthesized the p-acetyl, iodo, cyano, ethyl, and n-butyl analogues. These compounds complimented previous R and S isomers (unsubstituted and the p-chloro, methyl, nitro, and methoxyl analogues) synthesized in our laboratories from amino acids of known absolute configuration. The neurotoxic doses (TD50's), anticonvulsant potencies [maximal electroshock seizures (MES) and subcutaneous metrazole (sc Met) ED50's], protective indices (PI = TD50/ED50), and effects on minimal seizure threshold (iv Met) were compared with similar values concomitantly determined for clinically employed anticonvulsants. A parallel relationship was shown between neutotoxicity (TD50) and potency (ED50) for the R and S analogues. In most cases R isomers had a more rapid onset of action and possessed greater neurotoxicity and greater anticonvulsant potency.
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PMID:Para-substituted N-acetyl-L(S)- and -D(R)-alpha-amino-N-phenylglutarimides. A structure-activity study of substituent effects on steroselective anticonvulsant activity. 100 28

A light microscopic study was performed during the preictal period following the administration of methionine sulfoximine (MSO) to adult rats. The principal morphologic observation was the development of Alzheimer II astrocytes in gray matter, suggesting that the metabolic abnormality induced by MSO is initially confined to the astrocyte. In view of the association of the Aizheimer II astrocyte with hyperammonemic states, the drug toxicity may be secondary to the presence of ammonia. A possible mechanism involves astrocytes in the development of seizures produced by MSO.
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PMID:Alzheimer II astrocytosis following methionine sulfoximine. 116 49

The effects of hyperthermia induced seizures on the amount of Methionine-enkephalin (Met-E) in 15 day rat pups were examined. Animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 40.6 +/- 0.2 degrees C; at this time all of the animals had seizures. Elevated brain Met-E concentration was observed immediately after seizures. When the animals were exposed for 30 min to 27 degrees C environment maintained their normal body temperature throughout the experiments and no seizures were observed. The brain Met-E levels in this group were significantly lower than those observed in the animals exposed to 40 degrees C environment. These experiments suggest that enkephalinergic system may play a role in hyperthermia-induced seizures in the rat pups.
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PMID:Hyperthermia-induced seizures alter the levels of methionine-enkephalin in immature rat brain. 163 May 99

Stimulation of the perforant path, a major input to the hippocampal formation, produced significant decreases in the hippocampal levels of methionine enkephalin, dynorphin A(1-8) and an increase in the hippocampal level of gamma-aminobutyric acid. In addition, it was also observed that both mu and delta opioid receptor antagonists reduce wet dog shakes elicited by perforant path stimulation. The antagonists did not affect the changes in hippocampal levels of methionine enkephalin, dynorphin A(1-8) or gamma-aminobutyric acid. The results demonstrate that endogenous opioids are involved in the wet dog shakes elicited by perforant path stimulation. Since electrographic seizure activity occurs in the hippocampus in conjunction with perforant path stimulation-induced wet dog shakes, these data provide further evidence that endogenous opioid peptides play an important role in regulation of limbic system epileptogenic phenomena.
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PMID:Opioid mu and delta receptor antagonists reduce wet dog shaking elicited by perforant path stimulation. 167 26


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