Oxidative stress early in pregnancy and pregnancy outcome.

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.

Association of glutathione peroxidase activity with insulin resistance and dietary fat intake during normal pregnancy.

Glutathione peroxidase (GPx) is one of the most important antioxidant enzymes in humans. We studied the relationship between erythrocyte GPx activity and fasting serum insulin, plasma glucose, and C-peptide, estimates of insulin resistance from the homeostasis model of assessment as well as dietary fat intake in 408 normotensive nondiabetic pregnant women from Camden, NJ. GPx activity and the metabolic parameters were determined at entry to care (16 wk of pregnancy) and during the third trimester. GPx activity and the levels of insulin resistance increased significantly between entry and the third trimester. Statistically significant associations, all positive, were observed between GPx activity and fasting insulin (beta = 0.009, P < 0.001), glucose (beta = 0.975, P < 0.05), C-peptide (beta = 1.537, P < 0.01), and insulin resistance from the homeostasis model of assessment (beta = 0.209, P < 0.01). Dietary intakes of fat and polyunsaturated fatty acids were positively correlated with GPx activity as well. African Americans had significantly higher GPx activity, dietary fat, and polyunsaturated fatty acid intake than Hispanics and Caucasians. In conclusion, we demonstrated that normal pregnancy is associated with increased GPx activity and insulin resistance. There are ethnic differences in antioxidant response and dietary fat intake. Our findings suggest a potential link among antioxidant defenses, insulin resistance, and dietary fat intake.

Protein kinetics in stable heart failure patients.

Heart failure (HF) is a slow progressive syndrome characterized by low cardiac output and peripheral metabolic, biochemical, and histological alterations. Protein loss and reduced protein turnover occur with aging, but the consequences of congestive HF (CHF) superimposed on the normal aging response are unknown. This study has two objectives: 1) to determine whether there was a difference between older age-matched controls and those with stable HF (i.e., ischemic pathology) in whole body protein turnover and 2) to determine whether protein metabolism in liver and skeletal muscle protein turnover is impacted by CHF. We measured the whole body protein synthesis rate with a U-(15)N-labeled algal protein hydrolysate in 10 patients with CHF and in 10 age-matched controls. Muscle fractional synthesis rate of lateral vastus muscle was determined with [U-(13)C]alanine on muscle biopsies obtained by a standard percutaneous needle biopsy technique. Fractional synthesis rates of five plasma proteins of hepatic origin (fibrinogen, complement C-3, ceruloplasmin, transferrin, and very low-density lipoprotein apoliprotein B-100) were determined by using (2)H(5)-labeled l-phenylalanine as tracer. Results showed that whole body protein synthesis rate was reduced in CHF patients (3.09 +/- 0.19 vs. 2.25 +/- 0.71 g protein x kg(-1) x day(-1), P < 0.05) as was muscle fractional synthesis rate (3.02 +/- 0.58 vs. 1.33 +/- 0.71%/day, P < 0.05) and very low-density lipoprotein apoliprotein B-100 (265 +/- 25 vs. 197 +/- 16%/day, P < 0.05). CHF patients were hyperinsulinemic (9.6 +/- 3.1 vs. 47.0 +/- 7.8 microU/ml, P < 0.01). The results were compared with those found with bed rest patients. In conclusion, protein turnover is depressed in CHF patients, and both skeletal muscle and liver are impacted. These results are similar to those found with bed rest, which suggests that inactivity is a factor in depressed protein metabolism.