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

It has been suggested that aspartame facilitates seizures in man and animals because phenylalanine, one of its major metabolites, interferes with brain transport of neurotransmitter precursors and alters the synthesis of monoamine neurotransmitters such as norepinephrine, dopamine and/or serotonin. This facilitation is purportedly more likely in subjects predisposed to seizures. One test of this hypothesis would be to administer a wide range of aspartame doses to subjects whose seizure predisposition is dependent on abnormalities in monoaminergic function. Genetically epilepsy-prone rats (GEPRs) have a broadly based seizure predisposition that is based, in part, on widespread central nervous system noradrenergic and serotonergic deficits. Further reductions in the functional state of these neurotransmitters increases seizure severity in GEPRs. Thus, GEPRs appear ideally suited for testing the hypothesis that aspartame facilitates seizures by interfering with central nervous system monoamines. Oral administration of acute (50-2000 mg/kg) or sub-chronic (up to 863 mg/kg/day for 28 days) doses of aspartame did not alter seizure severity in either of two types of GEPRs. Not surprisingly, acute aspartame doses produced dramatic changes in plasma and brain amino acid concentrations. Hypothesized alterations in monoamine neurotransmitter systems were largely absent. Indeed, increases in norepinephrine concentration, rather than the hypothesized decreases, were the most evident alterations in these neurotransmitter systems. We conclude that aspartame does not facilitate seizures in GEPRs and that convincing evidence of seizure facilitation in any species is lacking.
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PMID:Amino acids, monoamines and audiogenic seizures in genetically epilepsy-prone rats: effects of aspartame. 164 76

The effects of three dipeptide analogues of N-acetylaspartylglutamate on seizures elicited by intracerebroventricular (i.c.v.) injection of L-glutamate (GLU), N-methyl-D-aspartate (NMDA), kainate (KA) and intraperitoneal (i.p.) injection of pentylentetrazol (PTZ) were studied in mice. N-Ac-L-Phe-L-Glu was active against myoclonic seizures induced by GLU and NMDA under simultaneous i.c.v. injection. All dipeptides were ineffective against KA and PTZ convulsions. The anticonvulsant activity and potency of N-Ac-L-Phe-L-Glu were similar to that of gamma-D-glutamylglycine (gamma-DGG) for excitatory amino acids (EAA) induced seizures. These results indicate EAA antagonistic activity among dipeptides which have L-glutamic acid on C-terminal and acetylated N-terminal.
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PMID:Dipeptides--analogues of N-acetylaspartylglutamate inhibit convulsive effects of excitatory amino acids in mice. 167 19

Male rats were treated by oral intubation with tyrosine (Tyr), at doses of 0.5 and 1.0 g/kg body weight, alone or together with 1 g aspartame (APM)/kg body weight, or an equivalent dose of phenylalanine (Phe; 0.5 g/kg body weight); the effects on seizures induced by an effective dose of metrazol (ED50) were observed. Tyr (0.5 g/kg body weight) had a protective effect against the Phe-potentiation of metrazol-induced clonic-tonic convulsions. At the same dose Tyr had no effect on the seizure-promoting activity of APM, but at 1 g/kg it reduced the proconvulsant potential of the sweetener. Analysis of the brain and plasma amino acid concentrations indicated that the Tyr to Phe ratio tended to be enhanced in Tyr-Phe treated rats compared with those treated with Phe alone. This ratio remained essentially constant in the brain of APM-treated rats, compared with those treated with APM plus 1 g Tyr/kg body weight, whereas an increase in this ratio in the plasma was observed. These results confirm that Tyr antagonizes the proconvulsant effect of Phe and APM and they further suggest that no simple relationship exists between the relative brain concentrations of the two amino acids and the response to metrazol convulsions.
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PMID:Effect of tyrosine on the potentiation by aspartame and phenylalanine of metrazol-induced convulsions in rats. 176 32

Derivatives of beta-casomorphin(1-5) at a dose level of 1 mumol/kg body weight were tested for their influence on pentylenetetrazol, picrotoxin, or electrically induced seizures after subcutaneous injection in mice. Tyr-Pro-Phe-D-Pro-Gly was found to facilitate pentylenetetrazol-evoked seizures, whereas desTyr derivatives Pro-Phe-D-Pro-Gly and Pro-Phe-Pyr exhibited anticonvulsant properties against those convulsions. The tripeptide was effective only 10 min after application. The beta-casomorphin derivative Pro-D-Phe-Pro-Gly was effective against electrically induced seizures. The protective action of this tetrapeptide lasted for about 5 h. Additionally, we tested the influence of orally administered Pro-Phe-D-Pro-Gly on pentylenetetrazol-induced seizures and Pro-D-Phe-Pro-Gly on electrically induced seizures. Both peptides were effective at a dose of 5 mumol/kg body weight.
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PMID:Influence of beta-casomorphin derivatives on chemically and electrically induced seizures. 205 99

Screening newborns for phenylketonuria (PKU) is a mandatory practice based on measuring a raised blood phenylalanine level. Many factors influence the rate of blood phenylalanine rise so that there are many pitfalls in detecting the 1:10,000 affected infant. About one percent of all babies tested proves to be "false positives." Two-thirds of those with persistent hyperphenylalaninemia prove to have classic PKU. Non-classic PKU with less intense, persistent hyperphenylalaninemia is due to different alterations in the enzyme, phenylalanine hydroxylase. Additionally, about one percent of the confirmed positive patients is due to either a defect in the synthesis or regeneration of the cofactor, tetrahydrobiopterin; these latter forms are not amenable to treatment with the low phenylalanine diet. Screening programs have developed directives regarding the timing and conditions for obtaining the specimens for testing. Specific confirmatory tests of those with positive results must be performed. Even so, about one in 70 affected babies is "missed," resulting in mental retardation, seizures, and neurologic deficits.
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PMID:Phenylketonuria: contemporary screening and diagnosis. 207 89

The role of the ventral hippocampal dentate granule neurons in the mu opioid receptor agonist-induced motor seizures and wet dog shakes was examined in this study. [NMe-Phe3-D-Pro4]morphiceptin (9.4 nmol) was injected into the left ventral hippocampus of rats 14 days after unilateral or bilateral colchicine (5 nmol/site) lesions of ventral hippocampal dentate granule cells and the subsequent behavioral and neuropathological responses were observed. [NMe-Phe3-D-Pro4]morphiceptin injected into control animals produced convulsions and numerous wet dog shakes that lasted for less than 1 h. [NMe-Phe-D-Pro4]morphiceptin-induced wet dog shakes were significantly reduced in unilateral colchicine-pretreated rats, and completely inhibited in bilateral colchicine-pretreated animals. In contrast, generalized motor seizures evoked by [NMe-Phe3-D-Pro4]morphiceptin were potentiated and prolonged in colchicine-pretreated animals as status epilepticus (sustained clonus of forepaws and head for more than 1 h) was observed in both unilateral and bilateral colchicine-pretreated animals but not in control rats. No morphological damage of granule or pyramidal cells was found in the ventral hippocampus of control animals following [NMe-Phe3-D-Pro4]morphiceptin injection. Colchicine treatment by itself produced a selective lesion of dentate granule cells. In colchicine-pretreated animals, [NMe-Phe3-D-Pro4]morphiceptin induced widespread seizure-related damage of CA3/CA1 pyramidal cells. These results suggest that dentate granule cells in the ventral hippocampus are essential for the elaboration of wet dog shakes. However, these neurons may play an inhibitory role in the spread of seizure activity within the hippocampus or limbic structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventral hippocampal dentate granule cell lesions enhance motor seizures but reduce wet dog shakes induced by mu opioid receptor agonist. 216 33

D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.
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PMID:Involvement of multiple opiate receptors in opioid kindling. 216 33

Concentrations of plasma amino acids and brain monoamines as well as pentylenetetrazol-induced seizures were monitored in CD-1 mice treated with aspartame in acute oral doses from 0 to 2500 mg/kg. One hour after administration aspartame produced increases in plasma concentrations of phenylalanine and tyrosine and modest reductions in concentrations of brain serotonin and 5-hydroxyindole acetic acid. However, these effects of the sweetener had no influence on the convulsive dose fifty (CD50) of pentylenetetrazol. Moreover, aspartame failed to alter the percentage of mice exhibiting seizures when exposed to an approximate CD50 of pentylenetetrazol. Finally, aspartame had no effect on brain norepinephrine or dopamine concentrations. In sharp contrast to previously reported studies, these observations suggest that aspartame, given in heroic doses, does not alter the propensity to seizure activity in CD-1 mice. We conclude that changes in plasma amino acids and brain serotonin produced by large oral bolus doses of aspartame are insufficient to result in functional deficits which might have the capacity to facilitate pentylenetetrazol-induced seizures.
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PMID:Aspartame fails to facilitate pentylenetetrazol-induced convulsions in CD-1 mice. 247 Jan 65

The effects of large doses of L-phenylalanine and of aspartame on seizure susceptibility and severity have been assessed in baboons Papio papio from Senegal which show photosensitive epileptic responses similar to primary generalised epilepsy in man. L-Phenylalanine, 50, 150 or 450 mg/kg, or aspartame, 300 or 1000 mg/kg, were administered orally. Peak plasma L-phenylalanine concentrations of approximately 2000 mumoles/l occurred 1-4 h after the highest dose of L-phenylalanine or aspartame. The plasma L-phenylalanine to large neutral amino acid ratio increased approximately 30-fold at this time. Compared with water administration there were no changes in epileptic responses 1-5 h after either treatment. In this primate model of epilepsy acute increases in plasma phenylalanine concentration are neither pro- nor anticonvulsant.
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PMID:Lack of effect of aspartame or of L-phenylalanine on photically induced myoclonus in the baboon, Papio papio. 250 88

A 28-year-old man with classical phenylketonuria had increased seizure frequency and rapidly progressive spasticity. There was a marked reduction of biogenic amine neurotransmitter metabolites in cerebrospinal fluid. Dietary therapy reduced serum phenylalanine levels, improved symptoms of hypertonicity, and cerebrospinal fluid neurotransmitter metabolites became normal. An adolescent male with classical phenylketonuria, treated by dietary restriction until age 6 years, was assessed for decreasing school performance at 18 years. Cerebrospinal fluid biogenic amine neurotransmitter metabolites were significantly reduced. Magnetic resonance imaging in both subjects showed multiple areas of increased signal intensity in cerebral white matter. Neuropathological changes in classical phenylketonuria have been characterized as a dysmyelinating or demyelinating process. Neurochemical studies show a defect in brain lipids and biogenic amine metabolism. In the past, dietary therapy was directed at reducing hyperphenylalaninaemia only during the first decade of life. This report, as well as other studies, indicates that dietary therapy should be lifelong in patients with classical phenylketonuria, in order to prevent progressive and insidious neurological deterioration in later life.
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PMID:Neurological deterioration in adult phenylketonuria. 251 76


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