Association of Thrombomodulin Gene Polymorphism (C1418T) With Coronary Artery Disease in Pakistani Population.

OBJECTIVES: To find out the association between Thrombomodulin gene polymorphism (C1418T) with coronary artery disease in population of Karachi, Pakistan. METHODS: This case-control study was conducted in Tabba Heart Institute in collaboration with the National Institute of Blood Diseases, Karachi. We compared C/T dimorphism in 92 cases with 90 control subjects by allele-specific amplification. The results of PCR were confirmed by Gene sequencing. All the laboratory methods were strictly in compliance with the international standards. All variables that were either statistically significant in the univariate analyses or potentially important with respect to prevention or biologically relevant variables were included in logistic-regression analyses. Potential confounding was assessed with the use of multivariate models adjusted for participant's characteristics and other major risk factors for coronary artery disease. All reported p values are two-tailed, with statistical significance at p value < 0.05. RESULTS: The frequency of CC, C/T and TT genotype was 81 (90%), 6 (6.7%) 3 (3.3%) in controls and 67 (72.8%), 20 (21.7%) and 5 (5.4%) in cases respectively. In cases group the CT/TT genotypes were found to be significantly highly represented among the patients with coronary artery diseases when compared with control group (p-value 0.009). CONCLUSION: TM C1418T polymorphism emerges as a risk marker in Coronary Artery Disease patients in the population of Karachi, Pakistan.

Reversal of difluoromethylornithine effects by the administration of putrescine in rats.

OBJECTIVE: To assess the reversal of Di-fluoromethyl ornithine (DFMO) effects by administration of putrescine on thyroid glands in rats. METHODS: The study was conducted on female rats weighing 248 to 320 grams at Quaid-e-Azam University, Islamabad in November end 2006. They were divided into three groups namely control group I treated with normal saline, DFMO treated group II at a dose of 50 mg/rat and DFMO and Putrescine group III received a combination of 50 mg/rat of DFMO and 150 microg of Putrescine, subcutaneously for five consecutive days. On sixth day, blood was collected by cardiac puncture and radioimmunoassay was performed to measure Serum T3, T4 and TSH levels in all groups. RESULTS: In group II there was a fall in T3, T4 concentration with significant rise in TSH concentration as compared to the control group. The combined administration of Putrescine and DFMO resulted in a rise in serum T3 and T4 with negligible fall in TSH. CONCLUSION: DFMO induced hypothyroidism was reversed by the administration of Putrescine. It is thus concluded that hormone mediated response in thyroid tissue can be altered by altering ODC responsiveness of target tissue of female rats.

Effect of difluoromethylornithine on thyroid function in rats.

BACKGROUND: A variety of stimuli cause a rapid increase in polyamine synthesis by increasing an enzyme ornithine decarboxylase required for the biosynthetic pathway of protein synthesis. Difluoromethyl ornithine is a selective inhibitor of this enzyme and hence arrests cell replication strikingly. Its effects on thyroid gland are studied with respect to change in animal's weight and levels of Triiodothyronine, Thyroxine and Thyroid stimulating hormone. The study was conducted to evaluate the inhibitory effects of Di-fluoromethyl ornithine (DFMO) administration on polyamine metabolism of thyroid gland in rats. METHODS: The study was conducted on rats weighing 248 to 320 grams, divided into control and DFMO treated group. A dose of 50 mg/rat was administered subcutaneously to the treated group for 5 consecutive days and placebo (normal saline) injections to control group. On sixth day, blood was collected by cardiac puncture and serum was separated. Serum T3, T4 and TSH were analyzed with the help of radioimmunoassay in both groups. RESULTS: In treated group there was a fall in T3, T4 concentration with significant rise in TSH concentration as compared to control group. CONCLUSION: DFMO (Difluoro methyl ornithine) decreases cellular proliferation of thyroid gland as is assessed by decrease in thyroid hormone levels. The hypothalamo pituitary thyroid axis however remains intact as is shown by a feedback rise in TSH concentration. DFMO can thus be employed for anti-neoplastic clinical trials on account of interference with activity of ODC (Ornithine Decarboxylase) fundamental for polyamine biosynthesis.