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

The effect of pharmacological doses of phenytoin (DPH) administered for a maximum of 28 days was studied in pregnant and nonpregnant rats as well as in 14- and 21-day fetuses. The following parameters were monitored in the adult rats: maximal electroshock seizures, serum DPH and folate, liver microsomal P-450, and 14C-DPH tissue distribution. 14C-DPH distribution was also evaluated in fetal tissues. Pregnant animals demonstrated an increase in anticonvulsant activity as well as increased serum concentrations of DPH throughout pregnancy and on the 7th post-partum day. Brain concentrations of DPH increased during pregnancy but had returned to the values in the nonpregnant group at the 7th post-partum day. Liver microsomal P-450 was decreased in pregnant animals receiving DPH at days 7 and 14 of pregnancy. Serum folate also decreased at day 14 of pregnancy in animals receiving DPH. Fetal tissue binding of DPH appeared to be related to serum concentrations of the drug at day 14. Teratogenic effects of DPH could be related to the increased serum and tissue concentrations of the drug observed during pregnancy as well as its effect on serum folate at day 14 of gestation.
 ...
PMID:Phenytoin: an evaluation of several potential teratogenic mechanisms. 89 92

This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.
 ...
PMID:Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets. 105 27

Piperonyl butoxide, a microsomal monooxygenase inhibitor, administered intraperitoneally to mice exerts peak anti-maximal electroshock activity and peak neurotoxicity at 5 and 7h, respectively. The median neurotoxic dose is 1,690 mg/kg. In the maximal electroshock seizure test, the median effective dose (ED50) is 457 mg/kg and the protective index (PI) is 3.69. In the subcutaneous pentylenetetrazol test, the ED50 is 443 mg/kg and the PI is 3.81. Piperonyl butoxide prevents seizure spread and elevates seizure threshold. Its PI compares favorably with PIs of clinically useful anticonvulsants.
 ...
PMID:Anticonvulsant activity and neurotoxicity of piperonyl butoxide in mice. 647 6

Mice of the DBA/2 (D2) strain are highly susceptible to sound-induced seizures at 21 days of age; whereas, mice of the C57BL/6 (B6) strain are resistant to these seizures. Although the difference in susceptibility to audiogenic seizures (ASs) between these two strains is inherited as a multiple-factor trait, an association was observed between susceptibility to ASs and the Ah locus. The Ah locus controls the inducibility of aryl hydrocarbon hydroxylase (AHH) activity by a number of aromatic hydrocarbons. B6 mice carry the Ahb allele and have inducible AHH activity; whereas, D2 mice carry the Ahd allele and have noninducible activity. Inducibility is inherited as a Mendelian dominant trait in crosses between these strains. Mice carrying the Ahb allele are generally less susceptible to ASs sat 21 days of age than are mice carrying the Ahd allele. The combined results from B6 X D2 recombinant inbred strains, congenic strains (where the Ahb allele was placed into the D2 genome and the Ahd allele placed into the B6 genome), the B6D2F1 X D2 backcross generation, and a random survey of various inbred strains, suggest that the association between these two traits is due to genetic linkage, rather than to pleiotrophy or to chance. A major gene that inhibits susceptibility to ASs appears to be closely linked to the Ah locus. This gene has been designated Ias, for inhibition of ASs. A large portion of the genetic variability of AS susceptibility may be due to the segregation of Ias.
 ...
PMID:Genetic linkage between the AH locus and a major gene that inhibits susceptibility to audiogenic seizures in mice. 734 53