Association between hyperhomocysteinemia and vascular dysfunction on molecular basis in acute and chronic models of experimental renal failure-possible role of folic acid

Hyperhomocysteinemia [HHcy] has recently been suggested as a risk factor for atherosclerosis [AS] in patients with chronic renal disease. Several mechanisms for HHcy-induced AS have been proposed but the molecular pathogenesis of this relation is still unclear. So far, there are no reports showing the changes in homocysteine levels in acute renal failure. We investigated whether HHcy is a common finding in acute and chronic renal failure, its relation to the pathogenesis of vascular dysfunction and its possible treatment by folic acid. 35 rats were divided into 5 groups [Gp]: Gp1 [sham operated]; Gp2 [acute ischemic renal failure]; Gp3 [treated acute ischemic renal failure]; Gp4 [chronic renal failure]; Gp5 [treated chronic renal failure]. Blood samples were collected for determination of urea, creatinine and homocysteine. Aortae were harvested for assessment of vascular endothelial growth factor [VEGF] expression and aortic content of tumor necrosis factor alpha [TNF]. Both acute [Gp2] and chronic [Gp4] models of renal failure showed higher homocysteine concentrations; increased VEGF expression and increased TNF alpha than Gpl. Folic acid treatment caused significantly lower homocysteine levels and VEGF expression in Gp3 and Gp5 than Gp2 and Gp4, while its reducing effect on TNF was only evident in acute treated model compared to Gp2. Homocysteine significantly correlates with creatinine and VEGF expression in acute models [Gp2 and 3], with urea, creatinine, TNF alpha in chronic model [Gp4] and with TNF alpha in Gp5. Our findings demonstrate that HHcy is evident in acute and chronic renal failure. Increased VEGF expression in acute failure and enhanced vascular inflammation in chronic failure could be possible mechanisms by which HHcy accelerates AS. However, the direct causal relationship between them needs further investigations. Folic acid decreases HHcy and could be useful in reducing cardiovascular risk factors in uremic patients

Effect of partial sleep deprivation on gastric functions in rats

Sleep deprivation has been associated with metabolic abnormalities, host defense failure and a variety of health problems including gastric discomforts. However, the effects of partial sleep deprivation on gastric functions have not been clearly elucidated. The present study aimed to investigate the effects of partial sleep deprivation for 2 weeks on gastric acid secretion, gastric mucosal integrity and gastric motility in rats. A specific apparatus was designed to induce sleep deprivation in our lab through random lighting of 4 lamps and ringing of a bell. Partial sleep deprivation was continued for 12 hours daily for 2 weeks. 80 male rats were used in this study, 40 as control and the other 40 were subjected to sleep deprivation. Control and partially sleep deprived rats were classified into 5 groups: in the 1[st] group, gastric contents were collected 3 hours after pyloric ligation and titrated for measurement of gastric free and total acid secretion. In the 2[nd] group, gastric mucosa was examined for detection of ulcers and calculation of mean ulcer index. In the 3[rd] group, calculation of ulcer index was done following oral administration of aspirin. In the 4[th] group, basal gastric content was determined and in the 5[th] group, gastric content after 4 hours fasting was determined and the values obtained were used to calculate percentage of food emptied through the 4 hours fasting period to the basal gastric content. Partial sleep deprivation significantly increased gastric acid secretion, induced the formation of gastric ulcers and increased ulcer index following aspirin administration. Sleep deprivation also inhibited gastric motility and emptying when compared to sleep undisturbed control group. Our results suggest that partial sleep deprivation could impair gastric functions especially gastric motility which has not been previously clarified