Mitochondrial pathway of apoptosis and related proteins in placenta of pregnant Egyptian women with pre-eclampsia

Apoptosis within the placenta is increased in pregnancies complicated by pre-eclampsia [PE].This study aimed at evaluating the mitochondrial pathway of apoptosis in placenta of pregnant women with pre-eclampsia and correlate it with severity and pregnancy outcome. Apoptosis was assessed by measuring DNA fragmentation%,Bcl-2, p53 and caspase-9 in placental tissues from 25 pregnancies complicated by pre-eclampsia, and 25 placentas of normal pregnancy [NP]. DNA fragmentation, p53 and caspase-9, were significantly increased while, Bcl-2 was significantly decreased in the placenta of pre-eclampsia group compared to control. No significant difference between mild and severe pre-eclampsia subgroups regarding these parameters could be found. DNA fragmentation was negatively correlated with Bcl-2 in PE group. Moreover, DNA fragmentation was negatively correlated with maternal age in both PE and control groups. A significant positive correlation between placental DNA fragmentation and gestational age in the NP group was observed. A significant negative correlation between caspase9 activity, and fetal weight in PE group was found. It can be concluded that Hypoxia and ischemia induced by pre-eclampsia, up regulate p53 and reduce Bcl-2 expression with activation of caspase-9 and increasing DNA fragmentation in placental tissue. These results implicate the mitochondrial pathway in enhancing apoptosis in preeclamptic placenta and affecting fetal outcome but not the severity

Antiphospholipid antibodies enhance monocyte procoagulant activity in primary antiphospholipid syndrome

Fifty cases with unexplained recurrent fetal loss were examined for antiphospholipid antibodies [APA] both by phospholipid-dependent coagulation tests to detect lupus anticoagulant [LA], and by a specific enzyme -linked immunosorbent assay [ELISA]. 18 patients were APA+ve : 6 [12%] by coagulation tests [LA+ve] and 12 [24%] by ELISA. Mononuclear cells were isolated from normal healthy volunteers by Ficoll-hypaque and cultured in RPMI-1640 medium [2 x 10[6] cells/ml]. LA+ve plasma, ELISA+ve plasma, and APA-ve control plasma were incubated with cultured cells for 4 hours in presence of lipopolysaccharide [LPS] at a concentration of 100 ng/ml. Significantly higher monocyte procoagulant activity [PCA] was induced by LA+ve and ELISA+ve plasma than by control APA-ve plasma. Immunoglobulin G [IgG] proteins were isolated from patient and control sera by anion exchange chromatography [DEAE Sephadex A50]and were incubated with cultured mononuclear cells under the same conditions. Antiphospholipid IgG [n = 5] induced significantly higher levels of PCA than control IgG [n = 6]. The stimulating effect of APA +ve plasma and antiphospholipid IgG on PCA was not detected in absence of LPS and was dependent on the presence of factor VII, but not factor IX, in the one stage clotting assay of PCA. This indicates that antiphispholipid antibodies probably increase monocyte PCA by enhancing the LPS-stimulated expression of tissue factor [TF]

Erythrocyte antioxidant enzymes and plasma copper, zinc and selenium in preeclampsia

The activities of superoxide dismutase [SOD] and glutathione peroxidase [GSHPx] were measured in the erythrocyte hemolysates of 25 primigravida preeclamptic [PE] patients [14 with severe and 11 with mild preeclampsia] during the third trimester. Plasma copper [Cu], zinc [Zn] and selenium [Se] levels were also assayed. The results were compared to normal pregnant values obtained from a control age matched primigravida normotensive group in the third trimester [n = 20]. There was insignificant lowering of SOD activity in PE than normotensive women. Normal GSHPx activity was found in total PE patients with insignificantly higher activities in severe than in mild PE group. While plasma Cu and Se were significantly higher in PE than normotensive group [p <0.01, p <0.001 respectively], Zn values did not differ between the two groups. The significant elevation of Se was evident both in severe and mild PE groups compared to normal pregnancy, but the elevation of Cu was only significant in the severe PE group and not in the mild PE group

High plasma lipid peroxides as a major predisposing factor for diabetic retinopathy

To examine the role of lipid peroxidation products in the pathogenesis of diabetic retinopathy, plasma malondialdehyde [MDA] levels were measured in type II non-insulin diabetic patients [n = 16] and without [n = 14] retinopathy and compared with a control group [n = 20] of normal subjects of the same age range [45 - 60 years]. Significantly elevated levels of MDA were found in diabetics with and without retinopathy, as compared with the control group [P <0.05]. There were also insignificantly higher MDA levels in diabetics with retinopathy than in those without retinopathy [P <0.05]. In addition, MDA levels were not correlated with fasting blood glucose, total lipids, triglycerides, total cholesterol, HDL and LDL cholesterol in diabetics with and without retinopathy. ADP and collagen-induced platelet aggregation were also tested and there were no statistical difference of the percent aggregation between diabetic groups and the control group [P >0.05]. Platelet function was neither related to MDA levels nor to the lipid profile of diabetic patients. The results of this study emphasized the role of lipid peroxides as a primary cause of vascular endothelial damage with eventual genesis of retinopathy. The administration of antioxidants in diabetics was consequently recommended