Angiotensin I converting enzyme gene polymorphism in glomerulonephritis

Since an insertion / deletion [I/D] polymorphism of the angiotensin converting enzyme [ACE] gene significantly influences circulating ACE levels, we examined the role of this polymorphism in glomerulonephritis. ACE genotypes were retrospectively analyzed in 39 patients with clinical and biopsy proven glomerulonephritis [27 with idiopathic and 12 with lupus nephritis] and compared with ACE genotypes of 36 age and sex matched healthy control subjects. The ACE variants were determined by PCR and the genotypes were classified as DD, ID and II. Patients with glomerulonephritis had significantly higher frequency of DD genotype when compared to the control [DD: ID+II 61.5%: 38.5% vs 25%: 75%, p = 0.001]. Still, patients with lupus nephritis had a higher frequency of DD genotype than those with idiopathic glomerulonephritis [although non-significantly [75% vs 55.6%, p > 0.05]]. The risk of presence of DD genotype was 5 times greater in patients with glomerulonephritis than the control [Odds ratio 4.8, 95% CI - 1.6 - 14.75]. Patients with glomerulonephritis had significantly lower frequency of I allele compared to the control [38.5% vs 75%, p = 0.001]. Patients with DD genotype were significantly younger and belong to the male gender compared to patients having ID+II genotypes [p < 0.05, p < 0.01 respectively]. Taken together, these findings suggest a strong association between the DD genotype and histopathologic proven glomerulonephritis and that it may be a genetic marker identifying patients at risk of developing such disease. Moreover, it may identify patients with systemic lupus erythematosus at risk of developing lupus nephritis. The presence of I allele may be protective against development of glomerulonephritis

Serum levels of interleukin 1 beta and interleukin 1 receptor antagonist in patients with diabetes mellitus. Associations with microvascular complications

To better understand the potential association of serum levels of interleukin- I beta [IL-1B] and interleukin-1 receptor antagonist [IL-1ra] with diabetic rnicroangiopathy, serum concentrations of IL-1B and IL-1ra were determined in 42 patients with diabetes mellitus [22 non Insulin dependent diabetes mellitus [NIDDM] and 20 insulin dependent diabetes mellitus [IDDM]] presenting with varying degrees of diabetic status and late complications. They were compared with 26 age and sex matched healthy subjects. Our results revealed that the concentrations of IL-1B and IL-1ra were elevated in diabetic patients versus control [Mean +/- SE 0.9 +/- 0.25pg /ml for IL-1B and 752.8 +/- 53.7pg / ml for IL-1ra in diabetics vs 0.08 +/- 0.04pg /ml for IL-1B and 446.6 +/- 40.5pg /ml for IL-1ra in the control, P = 0.01 and P< 0.0001 respectively]. Patients with diabetic retinopathy [n = 16] had the highest concentrations of serum IL-1B compared to those with neuropathy [n = 14] and to those with uncomplicated diabetes [n = 12] [Mean +/- SE 1.78 +/- 0.54pg /ml vs 0.37 +/- 0.32pg /ml and 0.35 +/- 0.16 pg /ml respectively, P = 0.05] IL-1ra levels were the highest In patients with diabetic neuropathy compared to those with retinopathy and uncomplicated diabetics [Mean +/- SE 905.9 +/- 95.2pg /ml vs 749.9 +/- 93.9pg /ml and 578.02 +/- 61.8pg/ml respectively. P<0.05]. Patients with proliferative diabetic retinopathy [n = 10] had significantly higher levels of IL-1B compared to those with non proliferative retinopathy [n= 6] [Mean +/- SE 2.7 +/- 0.71pg /ml vs 0.23 +/- 0.15pg /ml, P< 0.01]. IL-1ra / IL-1B ratio was lowest in patients with diabetic retinopathy especially the prolifertive type and highest in those with neuropathy with uncomplicated diabetics having intermediate values comparable to that of the control [P>0.01], Analyzing pooled data from diabetic patients, a weak negative correlation was found between IL-1B and IL-1ra [r = - 0.22, P> 0.05]. Interstirigly IL-lB was significantly correlated with HDL-cholesterol whereas IL-1ra was significantly correlated with serum triglycerides. IL-1ra/IL-1B ratio was significantly correlated with serum total cholesterol and HDL cholesterol. [r= 0.36 r = 0.38, r = 0.35 and r =-0.34 respectively]. Serum levels of IL-B and IL-1ra are elevated in diabetic patients with and without microangiopathy reflecting ongoing inflammation and macrophage endothelial cell activation. Elevated levels of IL-1B and decreased IL-1ra/IL-1B ratio point more to proliferative retinopathy whereas high levels of IL-1ra and IL-1ra/IL-1B ratio may give an idea about the presence of neuropathy

Trace elements in patients with acute cerebrovascular diseases

Free radical oxidation stress has been implicated in the pathogenesis of a variety of human diseases including stroke. Since trace elements act as cofactors for a variety of antioxidant enzymes, we decided to study the status of Copper. Zinc and Manganese in patients with acute cerebrovascular accidents. 45 patients [30 with cerebral infarction [CL] and 15 with cerebral haemorrhage [CH] and 44 control [C] were included in the study. Serum trace elements Cu. Zn and Mn were estimated using atomic absorption spectrophotometry. Routine liver and kidney function tests, pH, serum bicarbonate and random blood glucose were estimated for both patients and control CT scans were done for all patients. Patients with Cl and CH had significantly lower serum Cu, Zn and Mn than the control [P < 0.0001]. Patients with Cl tended to have higher serum Cu an Zn levels than those with CH, but the differences did not reach statistical significance [P > 0.05]. Serum Manganese concentrations were below detection Limit in either Cl or CH while in the control they ranged from 0.04-0.2 Ug/mI. Strong positive correlations were found between serum Cu and prothombin activity [r= 0.38. P < 0.009] and serum Zn and creatinine levels [r = 0.44, P < 0.002] in the whole cases with acute cerebrovascular accidents versus control. Trace elements involved in the antioxidant defense system are reduced in patients with acute cerebrovascular accidents. Replenishment of the deficient elements may help reduce the size of infarction and accordingly the functional disability in patients with strokes