Association between the 2756A> G variant in the gene encoding methionine synthase and myocardial infarction in Tunisian patients

BACKGROUND: Elevated plasma total homocysteine (tHcy), a risk factor for coronary artery disease (CAD), is due to defects in genes encoding for enzymes involved in tHcy metabolism or from inadequate status of vitamins involved in tHcy disposal. Methionine synthase (MS), a vitamin B(12)-dependent enzyme, catalyses the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetra-hydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter tHcy as well as folate levels which are independent risk factors for CAD. The influence of a common genetic polymorphism 2756A>G of the MS gene (MTR) on plasma tHcy, folate and vitamin B(12) levels and its relation to the risk of myocardial infarction (MI) in a Tunisian case-control study was investigated. METHODS: A total of 321 Tunisian patients with MI and 343 healthy controls were included in the study. The 2756A>G variant of the MTR was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Plasma tHcy was assessed with a fluorescent polarising immunoassay method. Plasma vitamin B(12) and folate were determined by microparticular enzyme immunoassay and ion-capture, respectively. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 1.9% for the GG genotype, 26.2% for the AG genotype and 72% for the AA genotype. Controls had a frequency of only 0.9% for the GG genotype, 18.7% for the AG genotype and 80.5% for the AA genotype (chi(2)=6.97, p=0.03). The MI patient group showed a significant higher frequency of the G allele compared to controls (0.149 vs. 0.101; OR 1.55; 95% CI 1.10-2.18; p=0.008). The association between the 2756A>G variant in the gene encoding MS and MI was no longer significant after adjustment for other well-established risk factors. When clinical and laboratory values were compared amongst genotypes in the study groups, no significant differences were noted. CONCLUSIONS: The present study showed a significant but not independent association between the 2756A>G polymorphism of the MTR (presence of G allele) and MI in the Tunisian population.     

In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats

It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.     

Severe pneumococcal community-acquired pneumonia admitted to medical Tunisian ICU

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP). There are no available data about this disease in Tunisian intensive care patients. The objective of this study is to describe the clinical and microbiological features of pneumococcal CAP and determine the prognostic factors. This is a retrospective cohort study of all pneumococcal CAP cases hospitalized in the medical intensive care unit (ICU) of Hospital A. Mami of Ariana (Tunisia) between January 1999 and August 2008. Included were 132 patients (mean age, 49.5 years; 82.6% males); 30 patients had received antimicrobial treatment before hospital admission. The mean of the Simplified Acute Physiology Score II was 32.9. All patients had an acute respiratory failure; 34 patients (25.8%) had pneumococcal bacteremic CAP. Among the isolated strains, 125 antimicrobial susceptibility tests were performed. The use of the new Clinical and Laboratory Standards Institute breakpoints for susceptibility when testing penicillin against S. pneumoniae showed that all isolated strains were susceptible to penicillin. The mortality rate was 25%. The need of mechanical ventilation at admission [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.67–6.94; P = 0.001), Sepsis-related Organ Failure Assessment (SOFA) score at admission ≥4 (OR, 3.1; 95% CI, 1.56–6.13; P = 0.001), and serum creatinine at admission ≥102 μmol/l (OR, 1.8; 95% CI, 1.02–3.17; P = 0.043) were independent factors related to ICU mortality. In conclusion, pneumococcal CAP requiring hospitalization in the ICU is associated with high mortality. All isolated stains were susceptible to penicillin.