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)

We present findings on an infant with neonatal megaloblastic anemia, homocystinuria, and neurologic dysfunction that included developmental delay and tonic seizures. There was no methylmalonic aciduria. Cyanocobalamin therapy was accompanied by complete hematologic and neurologic recovery, diminished homocystine excretion, and subsequently normal neurologic development. Cultured fibroblasts and lymphoblasts showed a reduced methionine synthase activity and a growth requirement for methionine. Cobalamin incorporation by the patient's lymphoblasts was normal, but the proportion of cellular methylcobalamin in the patient's lymphoblasts and fibroblasts were markedly reduced and that of adenosylcobalamin normal. The reduced methionine synthase activity was independent of assay reducing (thiol) conditions, but normal levels of activity accompanied culture of the patient's lymphoblasts in medium with markedly increased cobalamin concentration. The characteristics of the reduced methionine synthase of our patient differ significantly from that of the previously described infant with cobalamin E disease and suggest that genetic heterogeneity may characterize this mutation.
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PMID:Vitamin B12-responsive neonatal megaloblastic anemia and homocystinuria with associated reduced methionine synthase activity. 382 32

An international questionnaire survey has been conducted to define better the natural history of homocystinuria due to cystathionine beta-synthase deficiency and permit evaluation of treatment. Data were compiled for 629 patients. Among patients not discovered by newborn screening, B6-responsive individuals on the average have significantly better mental capabilities (mean IQ, 79) than do B6-nonresponsive individuals (mean IQ, 57). Time-to-event curves are presented for the other major clinical abnormalities produced by this disease. Each occurred at significantly lower rates in untreated B6-responsive than in untreated B6-nonresponsive patients, as shown by the following examples: (1) dislocation of optic lenses (at age 10, chances of dislocation: 55% and 82%, respectively); (2) initial clinically detected thromboembolic events (at age 15, chances of having had such an event: 12% and 27%, respectively); (3) radiologic detection of spinal osteoporosis (at age 15, chances of such osteoporosis having been detected: 36% and 64%, respectively); and (4) mortality (at age 30, chances of not surviving: 4% and 23%, respectively). Methionine restriction initiated neonatally prevented mental retardation, retarded the rate of lens dislocation, and may have reduced the incidence of seizures. Pyridoxine treatment of late-detected B6-responsive patients retarded the rate of occurrence of initial thromboembolic events. Following 586 surgical procedures, 25 postoperative thromboembolic complications occurred, six of which were fatal. Reproductive histories were reported predominantly for B6-responsive patients. Living offspring of either men or women patients had few abnormalities. The evidence is inconclusive whether untreated maternal cystathionine beta-synthase deficiency leads to excessive fetal loss. Only 13% of patients detected in screening programs of newborns and classified as to B6-responsiveness were B6-responsive, compared to 47% among late-detected patients. Current screening programs that identify neonatal hypermethioninemia may be preferentially failing to detect B6-responsive patients.
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PMID:The natural history of homocystinuria due to cystathionine beta-synthase deficiency. 387 65

We report the case of a boy with 5,10-methylenetetrahydrofolate reductase deficiency. The clinical features consisted of severe mental retardation, spasticity and seizures remaining static to 7 years of age followed by a phase of rapid deterioration and death at 7 1/2 years of age. The main biochemical findings were homocystinaemia, homocystinuria, a normal methionine level in plasma and cerebrospinal fluid, an increased excretion of methionine in urine and a very low level of folate in the cerebrospinal fluid. The activity of 5,10-methylenetetrahydrofolate reductase was greatly reduced in the patient's lymphocytes and liver.
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PMID:5,10-Methylenetetrahydrofolate reductase deficiency. Clinical and biochemical features of a further case. 393 30

Selectively substituted hydantoins 1 (15 examples), 4-hydroxy-2-imidazolidinones 2 (13 examples), 2-imidazolones 3 (10 examples), 2-imidazolidinones 4 (four examples), vicinal diamines 5 (two examples), and simple amino acid derivatives 6 (four examples) have been prepared and evaluated in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole seizure threshold (sc Met), and rotorod (Tox) tests. The medium effective doses (ED50) and the medium toxic dose (TD50) for the most active compounds are reported. In general, the most pronounced activity was observed for hydantoins 1 and protected amino acids 6. Within each series of compounds, enhanced anticonvulsant activity was often noted for compounds containing an aromatic group one carbon removed from a nitrogen atom. Among the most active compounds observed were the amino acid derivative N-acetyl-D,L-alanine benzylamide (6d) and the two 2-imidazolones 4-methyl-1-(phenylmethyl)-1,3-dihydro-2H-imidazol-2-one (3e) and 1-phenyl-1,3-dihydro-2H-imidazol-2-one (3g). Compound 6d proved to be slightly more potent in the MES test than phenacemide.
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PMID:Effect of structural modification of the hydantoin ring on anticonvulsant activity. 398 20

Rats and mice were submitted either to the convulsant methionine sulfoximine (MSO) alone or to MSO combined with actinomycin D or methionine respectively. Twenty-four hours after the intraperitoneal administration of these compounds, the animals were killed and tissue samples were prepared for electron microscopy. Methionine sulfoximine induced 'grand mal' type seizures which were abolished by methionine. In saline controls, glycogen was as beta particles located in the cytoplasm of astrocytes, i.e. in perikarya and processes. Liver glycogen was as perinuclear masses of alpha and beta particles or as alpha particles scattered in all the cytoplasm. When the rodents were treated with MSO, glycogen was as alpha and beta particles which invaded all areas of the astrocyte cytoplasm, this increase being tremendous in perivascular end feet. Actinomycin D slowed down the accumulation of glycogen particles while methionine completely abolished it. In any case, glycogen particles were confined to the astrocytes and were never seen in other types of cells. In liver, MSO induced an important decrease or a complete disappearance of glycogen particles. When the convulsant was combined with actinomycin D or with methionine, the figures looked like those of controls. These results have been discussed in relation to the mechanism of glycogenesis in central nervous system of rodents submitted to MSO.
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PMID:Glycogen particles in methionine sulfoximine epileptogenic rodent brain and liver after the administration of methionine and actinomycin D. 402 58

The short-term effects of administering testosterone propionate (TP) to 4-day female rats (androgenized females) on the synthesis of specific brain proteins were investigated. At various times after the intraperitoneal injection of TP or arachis oil, [35S]methionine was injected into the third ventricle and 1 h later proteins were extracted from the hypothalamus-preoptic area (H-POA) and analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Changes in synthesis of two 13,000-14,000 mol. wt. proteins in the 4-day rat brain were detected, and these changes appeared to be specific for the H-POA. In addition, silver staining revealed a 50,000 mol. wt. protein which was present in the male and androgenized female H-POA but not in the oil-treated female H-POA. An incidental, but potentially important finding, was the synthesis of a 77,600 mol. wt. protein in the H-POA of one animal which had several seizures during the experiment. These results show that changes in the synthesis of specific proteins occur in the H-POA of neonatal female rats within 8 h of TP administration and support the hypothesis that hormone-induced changes in brain protein synthesis may be involved in sexual differentiation of the brain.
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PMID:The short-term effects of testosterone on brain protein synthesis in 4-day-old rats: an electrophoretic study of proteins following intraventricular injection of [35S]methionine. 407 17

In this work we analyzed the immunoreactive-methionine-enkephalin (IR-Met-enkephalin) levels in several brain regions of rats sacrificed during the tonic extension, induced by acute treatment with pentylenetetrazol (PTZ). The results show an increased of IR-Met-enkephalin content in striatum but not in amygdala, hypothalamus, septum, hippocampus and cortex. To characterize whether this elevation of enkephalin levels in striatum corresponded to the releasable pool, we studied the in vitro efflux of this peptide in striatal slices of rats sacrificed during the seizures, in acute PTZ and in PTZ-kindled rats (kindling group I). In addition, PTZ-kindled rats were analyzed 24 h after the last stimulus (kindling group II). The striatal slices of acute group and kindling group I displayed a significant increase in the evoked release of IR-Met-enkephalin. However, no significant changes occurred from striatal slices of kindling group II animals. In vitro superfusion of GABA (100 microM) produced a approximately equal to 63% decrease in IR-Met-enkephalin released from striatal slices in both saline and acute PTZ-treated rats. Several studies suggest that opioid peptides may be released in the ictal phase of seizure in order to mediate some transient postictal behavior. Our results suggest that of several brain regions tested, only the striatal IR-Met-enkephalin may be released during the ictus to mediate postictal behavior in the acute PTZ treated and in PTZ-kindled rats. This effect may be regulated by the GABA system.
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PMID:Pentylenetetrazol-induced seizures produce an increased release of IR-Met-enkephalin from rat striatum in vitro. 407 66

Administration of the long latency convulsant, L-methionine-d,1-sulfoximine (MSO) results in an increase in brain methylation flux. We determined the effects of the anticonvulsant, diazepam (DZ) on MSO seizures and on brain levels of S-adenosyl-L-methionine (AdoMet) and S-adenosyl-L-homocysteine (AdoHcy) to indicate possible alterations in the brain methylation pathway. We report a dose related inhibition of MSO seizures by DZ. In addition, DZ significantly increased brain levels of AdoMet and AdoHcy and reversed the MSO-induced decreases in AdoMet and AdoHcy. DZ also blocked the MSO induced increase in the methylation index (AdoMet/AdoHcy). The data indicates an inhibition of MSO induced increases in brain methylation by DZ. Possible mechanisms for the effect of DZ on the cerebral methylation pathway are discussed.
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PMID:The effect of diazepam on brain levels of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine: possible correlation with protection from methionine sulfoximine seizures. 408 23

ACTH1-24 (0.5 or 10 micrograms = 0.17 or 3.45 nmol) and D-Ala2-Met-enkephalinamide (DAME; 10 micrograms = 17.05 nmol) were injected unilaterally into the hippocampus of freely moving rats to examine their effects on EEG activity, DC potentials and behavior. In 85% of the rats DAME elicited spreading depression (SD) with epileptiform discharges preceding and following the wave of SD. The following behavioral changes were recorded. DAME- and KCl-induced SD were accompanied by an increase in locomotor activity and wet-dog shaking behavior, which occurred only during the period of SD. After a wave of SD induced by DAME a biphasic pattern of activity, consisting of an initial depression in locomotion followed by hyperactivity, appeared in 59% of the rats. ACTH1-24 elicited SD in 13% of the rats tested. Neither the dosage of ACTH1-24 nor the strain of rats influenced the occurrence of SD and the incidence of ACTH-induced grooming behavior. SD induced by KCl also resulted in excessive grooming comparable to that induced by ACTH1-24. In the case of KCl-induced SD, grooming began directly after the injection of KCl and was frequently interrupted by short periods of locomotion. ACTH-induced grooming had a later onset and episodes of stretching and yawning were observed. It can be concluded that the behavioral effects of the injection of DAME are unspecific responses to SD and seizure activity. However, ACTH-induced grooming is not solely a byproduct of SD, since it occurred also in the absence of SD.
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PMID:Electroencephalographic spreading depression and concomitant behavioral changes induced by intrahippocampal injections of ACTH1-24 and D-Ala2-Met-enkephalinamide in the rat. 608 54

The cerebral concentrations of pyridoxal-5'-phosphate and divalent transition metal ions (Cu2+ and Zn2+) are appreciably higher in the seizure-susceptible strain of mouse (DBA/2J) than those in normal strains (CBA/Ca and Parkes ). By injecting metal ions intracranially and pyridoxal-5'-phosphate intraperitoneally, we could render the normal mouse prone to sound-induced epilepsy. The behaviour of the treated seizure-susceptible strain of mouse. The levels of glutamate and aspartate in its inferior colliculus were elevated and the concentration of gamma-aminobutyrate was lowered. Glutaminase inhibitors, 6-diazo-5-oxo-L-norleucine (DON) and 0-diazo-acetyl-L-serine (azaserine), and a transaminase inhibitor, 4-amino-3- isoxazolidone (L-cycloserine), when injected intraperitoneally, protected the seizure-susceptible mouse from undergoing convulsions, whereas pyridoxal-5'-phosphate and methionine sulphoximine, a glutamine synthetase inhibitor, exacerbated its epileptic condition. We propose a possible sequence of biochemical events associated with susceptibility to audiogenic seizures.
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PMID:Studies on sound-induced epilepsy in mice. 614 59


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