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)

C57BL/10Bg sps/sps mice display behavioral arrest, similar to generalized absence seizures. Compared with the parent strain C57BL/10Bg SPS/SPS, the activities of glutamate decarboxylase (GAD, E. C. 2.6.1.15), GABA aminotransferase (GABA-T, E. C. 2.6.1.19), aspartate aminotransferase (ASP-T, E. C. 2.6.1.1), and glutamate dehydrogenase (GDH, E. C. 1.4.1.3) in whole brain crude supernatant were significantly reduced in the sps/sps mice. Alanine aminotransferase activity (ALA-T, E. C. 2.6.1.2), was not altered in any of the strains, and normalization of GAD, GABA-T and GDH activities by that of ALA-T, further revealed significant differences between the normal strain (SPS/SPS), the heterozygotes (SPS/sps), and behavioral arrest (sps/sps) mice. These results suggest the possible involvement of GABAergic and glutamatergic neurotransmission in the absence-like behavior displayed by sps/sps mice. Open field behavior of C57BL/10Bg sps/sps mice is characterized by periods of marked inactivity which easily distinguish affected homozygotes, from their heterozygotes littermates.
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PMID:The C57BL/10Bg sps/sps mouse: a mutant with absence-like seizures; neurochemical and behavioral correlates. 239 34

The short-term effects of sodium valproate (VPA) on haem biosynthesis were assessed in a placebo-controlled crossover trial in eight healthy male subjects who ingested VPA 500 mg t.i.d. and matched placebo for 5 days. All showed augmented activity of leucocyte 5-aminolaevulinate synthase (ALA-S) activity, the rate-limiting enzyme of the haem biosynthetic pathway, following 3 and 5 days of VPA treatment (P less than 0.001). This was accompanied by increased urinary excretion of 5-aminolaevulinic acid (ALA; P less than 0.02) and total porphyrins (P less than 0.01). Mean (+/- SD) total VPA concentrations on day 3 (89 +/- 16 mg 1-1) and day 5 (91 +/- 22 mg 1-1) were within the target range for the drug. The long-term effects of VPA administration were examined in epileptic patients on established monotherapy. Leucocyte ALA-S activity (P less than 0.001), and daily urinary excretion of porphobilinogen (P less than 0.01) and total porphyrins (P less than 0.01) were all higher than in age-matched controls. No significant differences in erythrocyte ALA-dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase activities were found between the groups. These data suggest that VPA is porphyrinogenic in man and cannot be recommended as safe for seizure management in the porphyric patient.
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PMID:Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient. 313 Feb 56

delta-Aminolevulinic acid, an intermediate in heme formation, is elevated in certain human disorders including acute intermittent porphyria, tyrosinemia, and lead poisoning. It has been implicated in the central nervous system manifestations of these disorders via interactions with the GABAergic system. This potential interaction was examined by testing whether or not delta-aminolevulinic acid could alter the latency to seizure in mice. Seizures were induced in a variety of inbred strains of mice including C57BL, C3H, DBA mice and in a heterogeneous stock of mice. Flurothyl and 3-mercaptopropionic acid were used to induce seizures in the presence and absence of delta-aminolevulinic acid administered either i.p. (0.5 and 1.5 mmol/kg), or i.c.v. (4.5 and 450 nmol). delta-Aminolevulinic acid increased the latency to myoclonic and clonic seizures induced by flurothyl when administered i.p.; i.c.v. injections also delayed clonic seizures induced by flurothyl, and increased the latency to tonic seizures induced by 3-mercaptopropionic acid. The degree to which delta-aminolevulinic acid altered seizure latency in all tests was dependent on strain of mouse tested. These data support the conclusion that delta-aminolevulinic acid can act as an anticonvulsant agent, and mimic the effects of GABA. Moreover, there is genetic variation in the sensitivity of the various strains of mice to delta-aminolevulinic acid.
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PMID:Genetic differences in the effects of delta-aminolevulinic acid on seizure latency in mice. 377 Jan 19

Hereditary coproporphyria (Hepatic coproporphyria: HCP); HCP is the rarest and least recognized among hepatic porphyrias and is characterised by an excess of faecal and urinary excretion of coproporphyrin (mainly isomer III). The deficiency is in coproporphyrinogen oxidase. HCP was first described by Berger and Goldberg in 1955 and was considered an asymptomatic biochemical abnormality. It later became evident that HCP could provoke acute attacks similar to those of acute intermittent porphyria (AIP) and variegate porphyria (VP). Such episodes are often provoked by barbiturates, sulphonamides and other drugs, and include automatic symptoms (hypertension, tachycardia, abdominal pain, constipation), central (epileptic seizures, mental disturbances) and peripheral nervous system dysfunction. During acute attacks, urinary ALA (delta-aminole-vulinic acid) and PBG (porphobilinogen) are elevated just as in AIP and VP, however, a marked elevation of faecal COPRO (coproporphyrin) is diagnostic of HCP. Laparoscopic finding of our case showed a map-like appearance of the liver surface with slightly depressed dark-bluish areas and reddish-brown areas. The liver biopsy specimen showed red fluorescence under ultraviolet light. On HE staining, hydropic degeneration of the hepatocytes and many brown granules in the hepatocytes were seen. A part of the granules stained positive for iron. Schmorl's stain showed many needle-shaped crystallines. Erythropoietic coproporphyria (ECP); Heilmeyer and Clotten have described that elevated PROTO (protoporphyrin) and COPRO were found in the RBC of the patient. Topi et al. described two brothers with cutaneous photosensitivity similar to that of erythropoietic protoporphyria, but with elevated RBC PROTO and COPRO III in both. Very little is known about this disease.
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PMID:[Hereditary coproporphyria (Hepatic coproporphyria), Erythropoietic coproporphyria]. 761 59

We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy.
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PMID:Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome. 793 5

delta-Aminolevulinic acid dehydratase (ALAD) is the second enzyme in the heme biosynthetic pathway and catalyzes two molecules of delta-aminolevulinate (ALA), which is a potent agonist for GABA autoreceptors. ALAD has two common alleles and thus consists of three distinct isozymes, designated 1-1, 1-2, and 2-2. It has been shown recently that ALAD1 allele is associated with alcoholic liver injury. This association was ascribed to possible differences among isozymes in sensitivity to oxidized glutathione (GSSG), and this sensitivity is increased in erythrocytes of alcoholic patients. In the present study we measured erythrocyte ALAD activity from subjects with different ALAD genotype and found ALAD-1 is most sensitive to GSSG. We then investigated allele frequencies of ALAD in alcoholics (n = 126) and healthy controls (n = 115). For the control group, the frequencies were 0.94 (ALAD1) and 0.06 (ALAD2) and for the overall alcoholic group, 0.91 (ALAD1) and 0.09 (ALAD2). There were no significant differences in allele frequencies at the ALAD locus between the two groups. Subtyping the alcoholics according to the presence or absence of delirium tremens, hallucinosis, withdrawal seizure or liver cirrhosis failed to show statistically significant differences in the allele frequencies. We conclude that our data do not support the evidence of an allelic association between the ALAD1 and alcoholism.
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PMID:[Lack of association between alcoholism and alleles in the delta-aminolevulinic acid dehydratase (ALAD) gene]. 808 Apr

Certain of the hepatic porphyrias are classified as belonging to the acute hepatic prophyrias, namely acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP) and ALA-dehydrase deficiency. The common feature of all acute hepatic porphyrias is the sudden onset of neurological symptoms. The whole syndrome consists of acute abdominal pain crises with autonomic dysfunction, global or focal central nervous system involvement and a predominantly motor polyneuropathy. Mono- or oligosymptomatic manifestations of acute porphyrias occur and are probably underestimated. The laboratory diagnosis of porphyria depends on the measurement of porphyrin precursors in urine, whereas the measurement of porphyrins in urine and feces is essential for evaluation of the porphyria type. Enzyme measurements are used to identify asymptomatic family members whose quantitative excretions of porphyrins are normal. At present the pathogenesis of neurological manifestations of acute porphyrias remains an unsettled question. The major hypotheses are discussed in this paper. The most important precipitating factor in acute hepatic porphyrias is drug ingestion. As many new drugs have not been in use for sufficiently long periods to assess their porphyrogenic activity, it is safer to avoid drugs in patients with porphyria. The most effective treatment of porphyria attacks is the administration of heme. Among the porphyria patients with epileptic seizures requiring antiepileptic medication, treatment with bromides should be taken into consideration.
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PMID:[Acute hepatic porphyria and its neurological syndrome]. 857 Nov 13

In the present study the potential neurotoxicity of diphenyl diselenide, as measured by the manifestation of seizures in rat pups (postnatal days, PND, 12-14) was evaluated. The results suggest that the latency for the appearance of tonic-clonic seizures, characterized by rearing and falling of rat pups body, was dependent of the dose tested. Diphenyl diselenide at high doses induced seizure episodes in rat pups. The highest dose of diphenyl diselenide (500 mg/kg) increased the levels of lipid peroxidation and catalase activity as well as decreased delta-ALA-D (delta-aminolevulinate dehydratase) and Na(+), K(+) ATPase activity in the brain of rat pups. Our results indicate the possible involvement of free radical oxygen injury in diphenyl diselenide-induced seizures. The data obtained with the dose of 150 mg/kg in the brain of rats that exhibited seizures are: an increase in lipid peroxidation levels; the lack of effect on catalase activity; an inhibition of delta-ALA-D activity, supporting that the enzyme activity is more sensitive than other parameters analyzed as an indicator of oxidative stress. The lowest dose of diphenyl diselenide emphasizes the relationship between the appearance of seizures and the latency for the onset of the first episode. Taken together, this paper could add to our understanding of diphenyl diselenide neurotoxic effect demonstrated by the appearance of seizures which are, at least in part, related to the oxidative stress.
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PMID:Involvement of oxidative stress in seizures induced by diphenyl diselenide in rat pups. 1732 Aug 26

The aims of the present study were to investigate the possible involvement of glutamatergic system in seizures induced by diphenyl diselenide in rat pups (postnatal day, 12-14) and to evaluate the role of oxidative stress in seizures induced by diphenyl diselenide/glutamate. Glutamate (4 g/kg of body weight) administered in association with diphenyl diselenide (500 mg/kg of body weight) increased the latency for the appearance of the first seizure episode, reduced lipid peroxidation levels and catalase, Na+,K+-ATPase and delta-ALA-D activities. At the lowest dose (5 mg/kg of body weight), diphenyl diselenide reduced the appearance of seizure episodes induced by glutamate but did not alter the latency for the onset of the first episode. Glutamate uptake was inhibited in glutamate, diphenyl diselenide (the highest dose) and in the association of diphenyl diselenide (both doses) and glutamate groups. Pre-treatment with a N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (5S,10R-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), significantly prolonged the latency for the onset for the first convulsive episode. A non-NMDA receptor antagonist, DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect seizures induced by diphenyl diselenide. The results of the present study demonstrated that: (a) when diphenyl diselenide and glutamate were administered concomitantly in pups, glutamate was the main responsible for the neurotoxic effects; (b) oxidative stress was not involved in glutamate-induced seizures; (c) NMDA glutamatergic receptors, were at least in part, involved in diphenyl diselenide- induced seizures; and (d) diphenyl diselenide, at the lowest dose, protected seizures induced by glutamate.
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PMID:Diphenyl diselenide-induced seizures in rat pups: possible interaction with glutamatergic system. 1808 Jan 89

One of the most frequent precipitating factors for attacks of porphyria is the administration of drugs. Use of drugs with porphyrinogenic potential often worsens the condition and often poses a therapeutic dilemma. A 23-year-old female patient presented to the casualty room with abdominal pain, chest pain and vomiting. Her past medical history was significant with episodes of generalised abdominal pain. The patient was initially treated for her abdominal pain and vomiting. She developed seizures and was treated with diazepam and phenytoin. Based on the positive investigation reports (positive urine porphyrins, elevated urine ALA and positive porphobilinogen) and symptoms, a diagnosis of acute intermittent porphyria (AIP) was done. Before the diagnosis of AIP was made, the patient was treated with drugs which are not considered to be safe in porphyric patients, such as phenytoin, metoclopramide, and diclofenac. The use of these drugs probably contributed to the initial worsening of the patient's clinical condition. After the diagnosis of AIP was made, the patient was treated with safer alternatives; gabapentin as the antiepileptic agent, promethazine as antiemetic, and propanalol as the antihypertensive agent. Withdrawal of the unsafe agents and symptomatic management with the safer alternatives contributed to the recovery of the patient. Along with the case report and the observations made on the various drugs used in the patient, the importance of the various information sources available on the safety potential of these agents is discussed. The observations with the drugs used in our case will be a useful addition to the existing information on the safety of these agents.
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PMID:Drug use in porphyria: a therapeutic dilemma. 1894 96


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