Impact of gene polymorphism on therapeutic drug monitoring of phenytoin and outcome in epileptic patients

This work was performed to explore the effect of polymorphism in multidrug resistant gene [MDR1] on plasma phenytoin levels and patients' outcome to evaluate its involvement in drug resistance and toxicity that is usually associated with antiepileptic drugs. Therefore, we genotyped the MDR1 in 100 patients, suffering from partial or generalized tonic-clonic seizures and receiving phenytoin, and 50 healthy control subjects. Steady state plasma phenytoin levels were also determined in the epileptic patients. Patients were evaluated after three and six months and were classified either as drug resistant patients or responsive patients. Results revealed 37 patients with drug-responsive epilepsy and 63 patients with drug-resistant epilepsy. Genotyping of our patients and control subjects revealed a genotype distribution of [CC, CT, TT: 55.50%, 38.00%, 6.50%] for drug resistant patients, [CC, CT, TT: 13.50%, 46.00%, 40.50%] for drug responsive patients, and [CC, CT, TT: 24.00%, 48.00%, 28.00%] for the control subjects. Patients with drug-resistant epilepsy were more likely to have the CC than the TT genotype compared with either responsive patients [P< 0.0001] or control [P <0.0001]. The C polymorphism was overrepresented among patients with drug-resistant epilepsy as compared with either those with drug-responsive epilepsy [P <0.001] or control [P <0.001]. Out of the total 100 epileptic patients; 13 patients had their plasma phenytoin levels exceeding the maximum safe concentration. These 13 patients were more likely to have TT genotype than the CC genotype compared with the remainder patients who had their plasma phenytoin levels 0.05] or allele frequency [P>0.05]. In Since most of the antiepileptic drugs are MDR1 substrates, thus the MDR1 is an important candidate gene potentially influencing the response to antiepileptic drugs. Our findings suggest that using genotype data may make it possible to safely reduce the time required to reach an effective dose. Therefore, it is a priority to assess the utility of dose adjustment on the basis of genotype for these medicines that are substrates for this gene

protective role of the neurohormone [melatonin] and garlic against paraquat toxicity in albino rats

This study was carried out on 150 rats of both sexes to investigate the possible protective role of melatonin and fresh garlic homogenate [FGH] either alone or in combination against paraquat-induced toxicity. The rats were divided into ten equal groups: One negative control, two positive controls and seven test groups. The test groups received paraquat 60 ng/kg single dose orally, melatonin 20 mg/kg orally and FGH 5 g/kg orally. Both melatonin and FGH were given with paraquat under variable conditions of timing. The rats were sacrificed 48 hours after paraquat administration. Liver and kidney functions were investigated in addition to light microscopic examination of the lung, liver and kidney. The study showed that the administration of melatonin and FGH either alone or in combination with paraquat did not show any significant improvement in paraquat- induced toxicity. On the other h and, melatonin or FGH 24 hours after paraquat showed a significant change in paraquat-induced damage, but melatonin appeared to be more potent than FGH

Effect of some vitamins administration on methotrexate-induced damage of rat jejunal mucosa

This work aimed to evaluate the prospective effect of some antioxidants against MTX toxicity. 90 adult albino rats, kept on a standard diet and water, were divided into 5 groups. Group I served as a control group, group II received methotrexate [MTX] in a dose of 2.5 mg/kg b.wt. for 3 consecutive days, group III received MTX concomitantly with vitamin E 600 mg/kg, group IV received MTX concomitantly with vitamin A 5000 IU/kg, and group V received MTX concomitantly with both vitamin E and vitamin A. The results were statistically analyzed and revealed that jejunum of rats with MTX [group I] showed significantly short, wide villi and deep crypts, marked lymphocytic infiltration in epithelium and lamina propria of the villi. Union of the villi either at the bases or their tips was a protective mechanism to decrease the oozing of plasma from the tissue to the lumen. Goblet cells showed decreased intensity of alcian blue stain. Alkaline phosphatase reaction was reduced at the brush border of the villi despite of its increased serum level. The electron microscopic results revealed markedly swollen mitochondria, reduction in the number and size of microvilli at the brush border, the nuclei showed signs of degeneration. Laboratory investigation revealed a significant reduction of TLC, PC, a significant elevation of serum AST, ALT, ALP, urea and creatinine in group II when compared with control group. In the same time, there was significant improvement of the previous parameters in groups III, IV and V when compared with MTX group. Concomitant administration of vitamins E and A with MTX gave the best protection against MTX-induced damage of both intestinal mucosa and laboratory parameters