Apoptosis of cardiomyocytes assessed by a novel apoptotic marker [annexin V] and the role of vitamin E in cardioprotection in diabetic rats

Recently it has been shown that annexin V is an apoplolic marker in the heart. The aim of the present study was to explore whether annexin V content in the heart changes during diabetes in order to use it as a prognostic tailor in diabetic cardiac affection. In addition, the study attempted to show the effect of treatment of insulin and vitamin E [300mg and 600mg/Kg] used separately or in combination. The study included 70 male albino rats weighing I70-200gm. They were divided into the following groups of 10 rats each: Group I [cont]: Control group, Group II [DM]: Diabetic, untreated group. Diabetes was induced by intraperitoneal injection of streptozotocin [stz] at a dose of 40mg/kg body weight, Group III [Ins]: Diabetic group, treated with 1 unit insulin injected subcutaneously, Group IV [E-300]: Diabetic group, receiving 300mg/kg vitamin E injected intramuscularly, 3 times/week for one month, Group V [E-600]: Diabetic group, receiving vitamin E i.m injection at a dose of 600mg/kg, 3 times/week for one month, Group VI [I+E-300]: Diabetic group treated with insulin and vitamin E [300mg/kg/dose] and Group VII [I+E-600]: Diabetic group treated with insulin and vitamin E [600mg/kg/dose]. Annexin V and inducible nitric oxide synthase [iNOS] were examined in the hearts of animals by RT-PCR. Also, cGMP, malondialdehyde [MDA], glutathione peroxidase [GPX] and cardiac enzymes were measured. There were three major new findings in the present study. First; annexin V levels were significantly elevated in the heart of diabetic rats compared to controls. This elevation in annexin V content indicates that apoptosis is the basis of cardiac injury as shown by the elevated cardiac enzymes AST, ALT and CPK. Second, levels of iNOS protein of the heart were elevated in diabetic rats. On the basis of theses findings, we can suggest that inflammation could play a role in the pathogenesis of diabetic cardiomyopathy in type I diabetes. Third, the effect of various types of treatment of diabetes which were used here showed the beneficial effects of the use of the antioxidant, vitamin E. These results suggest that annexin V can be used as a prognostic factor in cardiac affection in DM. In addition, they provide further evidence that pharmacological intervention by different antioxidants may have significant implications in the prevention of the pro-oxidant features of diabetes

Correlation between level of soluble receptors of advanced glycated end products [sRAGE] and gene polymorphism of glycine 82 serine [G82S] in patients with rheumatoid arthritis

The receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA. To evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity. The study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine 82 serine [G82S] of the RAGE gene. RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE. The levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine 82 serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions

Correlation between level of soluble receptors of advanced glycated end products [sRAGE] and gene polymorphism of glycine 82 serine [G825] in patients with rheumatoid arthritis

Background: the receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA

Objective: to evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity

Methods: the study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine82serine [G82S] of the RAGE gene

Results: RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE

Conclusion: the levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine82serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions