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Objectives: To evaluate oxidative and antioxidative status in pregnant diabetic women between 26 and 32 weeks of gestation. Design and Methods: Free and total malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and vitamins A and E were determined in plasma and erythrocytes of 54 pregnant women. Among these, 27 were diabetics with either gestational diabetes mellitus (GDM), sub-group I, or previous insulin-dependent diabetes mellitus (type 1 diabetes), sub-group II. The other 27 patients were controls. Fasting plasma glucose and HbA 1c levels were determined in all women. Results: HbA 1c levels, plasma-, and erythrocyte-free MDA levels were significantly higher in all diabetic women and in both sub-groups than in controls. Plasma vitamin E and erythrocyte vitamin A levels were significantly lower in all diabetic women than in controls. Moreover, GPX and SOD activities were significantly reduced in all diabetic women, GPX in both sub-groups and SOD only in type 1 diabetes. Conclusions: The increased oxidative stress we demonstrated in pregnant women with previous type 1 diabetes or with GDM should be monitored by strictly controlling blood glucose during pregnancy with stringent recommendations and perhaps antioxidant supplementation.

Objective: To analyse the relation between antioxidant vitamins A, E, and malondialdehyde (MDA) lipoperoxidation product plasma concentrations with incident dementia. Design: A nested case–control within the PAQUID (Personnes Agees QUID) cohort. Setting: The PAQUID population-based prospective cohort in southwestern France. Subjects: Among 626 subjects with blood collection at baseline, 46 developed a dementia during the follow-up and were considered to be cases. Each case was matched (on age and sex) to three controls. Results: Plasma vitamin E concentrations were lower among cases (mean value at 22.62 μmol/l (s.d.: 7.38) vs 24.99 (s.d.: 6.73 among controls). The same trend was observed for vitamin A concentrations, but the difference was not significant. On the contrary, MDA concentrations tended to be higher (mean value 1.35 μmol/l (s.d.: 0.53) vs 1.23 (s.d.: 0.44)) among cases. In logistic regression models, plasma values were split into tertiles. Adjusted for confounders, the risk of dementia was significantly increased in the lowest vitamin E tertile (≤21.0 μmol/l) (OR=3.12, P=0.033) compared to the highest one (≥25.5 μmol/l). The risk of Alzheimer's disease was also increased, with borderline significance (OR=3.06, P=0.053). Risks associated with vitamin A were nonsignificant. Similarly, there was a trend to an increased risk of dementia in the highest tertile of MDA (OR=1.67, P=0.31). Conclusions: These results suggest that subjects with low plasma vitamin E concentrations are at a higher risk of developing a dementia in subsequent years.

Increased peroxidation of lipids in red blood cells (RBC) in patients with advanced chronic renal failure (CRF) reflects increased generation of reactive oxygen species (ROS), which may contribute to the metabolic damage induced by CRF and to its progression. We have evaluated parameters indicative of lipoperoxidation (LPO) of RBC at baseline in patients with CRF compared to controls, and the effects of a very low protein diet supplemented with amino and keto acids and vitamins A, C, E (VLPD) over a 6-month period. The presence of peroxidation damage in CRF patients before the administration VLPD was demonstrated by elevated levels of free malondialdehyde (MDA) (p.0003) and decreased levels of polyunsaturated fatty acids (PUFA), particularly C20:4 (p.001), C22:4 (p.0001) and C22:5 (p.0001) when compared to controls. Similarly, RBC vitamin E content was significantly decreased (p.0001) while enzymatic activities were unalterated. VLPD reduced erythrocyte LPO as suggested by (a) decreased levels of free and total RBC MDA (p.003 and p.03, respectively), (b) increased levels of PUFA, particularly C22:4 and C22:5 (p.003 and p.03, respectively), and (c) increased levels of vitamins A and E (p.001 and p.04, respectively) as compared to prediet results. Antioxidant enzyme activities were not modified. These results suggest that VLPD has a protective role against LPO of erythrocytes in patients with CRF.

In 14 patients undergoing haemodialysis, lipoperoxidation (LPO) processes were determined in plasma and red blood cells (RBC) before and after a dialysis session by determining (a) the direct substrate, polyunsaturated fatty acids (PUFA); (b) the end product of LPO, malondialdehyde (MDA); and (c) the hydrophobic antioxidant systems, vitamins A and E. In plasma before dialysis, linoleic and arachidonic acid, and the antioxidant vitamin E, were significantly lowered as compared to the healthy controls (p < 0.05). On the contrary, the free MDA level was enhanced (p < 0.05). These results were emphasized by a dialysis session. In RBC of these patients, no difference in linoleic acid, free MDA, or vitamin E level were observed before or after dialysis when compared to controls. However, only vitamin A was significantly higher in haemodialysis patients (before and after dialysis) and in renal failure patients (p < 0.05) than in the healthy control group. The present results suggest that increased RBC vitamin A may offer some degree of protection against oxidative stress in erythrocytes, but not in plasma where LPO is demonstrated.

An association between impaired maternal vitamin A status during pregnancy and increased risk of mother-to-child transmission (MTCT) of HIV has been documented in observational studies.1 However vitamin A supplementation during pregnancy has not shown any efficacy in reducing the overall MTCT risk.2,3 WHO recommends vitamin A supplementation in all women within the first six weeks after delivery, complementary to the child supplementation4. Limited information is available on vitamin A in breastmilk of West-African women and its association with the risk of MTCT. We evaluated such a relationship in Cote d’Ivoire and Burkina Faso. A secondary objective was to assess the association between milk and maternal serum retinol levels at day 45 post-partum.

Chronic production of reactive oxygen species (ROS) and/or deficiency in the antioxidant defense system are observed in non-insulin-dependent diabetes mellitus (NIDDM) patients. As an adjunct to the usual indirect parameters for evaluating oxidative stress, we assessed the feasibility of oxyradicals detection in venous blood by electron spin resonance spectroscopy (ESR). Detection of the ascorbate pool was also performed using the validated ESR analysis of the ascorbyl free radial (AFR)-dimethyl sulfoxide (DMSO) complex.Plasma lipoperoxidation was characterized by higher levels of total MDA (1.50 +/- 0.08 nmol/L), lower levels of GSH (0.54 +/- 0.02 mmol/L) and of vitamin A (2.13 +/- 0.52 mumol/L) in the NIDDM group than in the controls (0.75 +/- 0.05 nmol/L, 0.90 +/- 0.05 mmol/L, 3.52 +/- 1.04 mumol/L, respectively). Improvement of the ESR measurement of oxyradical adducts has been previously obtained by addition of a new sensitive nitrone (DEPMPO), which acts as a spin-trap. However, in our experiment the ESR signal-to-noise ratio was too low to detect significative oxyradicals adducts in total venous blood of NIDDM patients having a weak production of ROS. A significant difference (p0.002) was observed in DMSO/AFR index between controls (24.00 +/- 4.10 nmol/L) and NIDDM patients (7.28 +/- 2.36 nmol/L) suggesting ascorbate depletion related to the free radical production.The DMSO/AFR index could be an interesting additional marker of oxidative stress during a chronic production of ROS.

OBJECTIVE To evaluate erythrocyte lipid peroxidation (LPO) before and after an adaptive short-term insulin therapy in NIDDM patients who were chronically hyperglycemic. RESEARCH DESIGN AND METHODS Twenty-six patients with NIDDM (mean HbA1c, 11.28%) aged 53.04 ± 2.03 years were submitted for 3 days to constant intravenous glucose and continuous insulin perfusion at an adaptable rate to maintain glycemia within the normal range. An evaluation of LPO at baseline and after euglycemic insulin therapy was determined by erythrocyte free and total malondialdehyde (MDA) levels, polyunsaturated fatty acid (PUFA) percentage, vitamin E and glutathione content, and the following antioxidant enzymatic activity determinations: glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). Fasting serum glucose, HbA1c, triglycerides, cholesterol, and HDL cholesterol levels were also determined at these time points. RESULTS At baseline, erythrocyte free and total MDA were significantly higher in NIDDM patients than in control subjects (11.14 ± 0.80 vs. 1.74 ± 0.11 nmol/g Hb [P < 0.0001] for free MDA; 18.04 ± 1.79 vs. 7.85 ± 0.55 nmol/g Hb [P < 0.0001] for total MDA). PUFAs, particularly C20:4 and C22:5, were increased (14.69 ± 0.34 vs. 12.03 ± 0.31 and 2.31 ± 0.04 vs. 1.71 ± 0.03% of total fatty acids, respectively). Vitamin E and glutathione were reduced significantly (6.16 ± 0.61 vs. 14.84 ± 0.64 nmol/g Hb and 0.42 ± 0.04 vs. 0.97 ± 0.06 mmol/l, respectively). No difference was observed for the enzymatic activities. After euglycemic insulin therapy, triglycerides significantly decreased compared with baseline concentrations (1.55 ± 0.13 vs. 2.42 ± 0.22 mmol/l; P < 0.001), whereas other lipidic parameters were unchanged. Free MDA significantly decreased (8.60 ± 0.76 vs. 11.14 ± 0.80 nmol/g Hb [P < 0.01]), while vitamin E increased (7.93 ± 0.73 vs. 6.16 ± 0.61 nmol/g Hb [P < 0.05]). No difference was observed for PUFAs, glutathione, or total MDA. CONCLUSIONS The observed erythrocyte LPO in NIDDM decreased after a short-term adaptive insulin therapy. This decrease could be principally attributed to the normalized glycemia that reduces reactive oxygen species (ROS) production, which in turn may explain the increase in erythrocyte membrane vitamin E and the decrease in MDA. This study shows the value of a euglycemic environment in NIDDM to reduce LPO and, at long range, to minimize clinical diabetes complications.

Objective: To investigate red blood cell (RBC) and plasma fatty acids (FA) in HIV-positive patients in relation to oxidative stress and nutritional or immunologiical status. Design and Methods: FA, plasma selenium, vitamins A and E were measured in 95 patients divided into four groups according to CD4 cells. Results: Poly- and di-unsaturated FA (PUFA, DUFA) decreased and saturated FA (SFA) increased in RBC in the patients below 400/mm3 and in plasma in the patients below 50/mm3 RBC SFA correlated to CD4 cells, PUFA to MDA. Unlike vitamin E, plasma vitamin A and selenium decreased in most groups. Plasma SFA and MUFA correlated negatively to selenium and PUFA and DUFA to vitamin E. No correlation was found between PUFA and nutritional markers. Conclusion: FA seem to be modified during HIV infection by oxidative stress and disease evolution, but not by denutrition.

International audience; The effects of almitrine on ATPase/ATPsynthase previously described in beef heart mitochondria (Rigoulet et al. (1990) Biochim. Biophys. Acta 1018, 91-97) are also observed in liver mitochondria isolated from rats older than 7 weeks. In contrast, in rats younger than 5 weeks, almitrine at the same concentration has no effect on the ATPase/ATPsynthase complex. This age-dependent action of almitrine is well correlated with age-dependent modifications of two fatty acids: linoleic and docosahexaenoic acids. The possibility of a change in H+/ATP stoichiometry of the ATPase/ATPsynthase induced by almitrine seems related to more general modifications of membrane properties during growth of the rat.

The lipid composition of whole brain hemispheres and subcellular fractions of European Hamsters ( Cricetus cricetus ) was investigated at four different periods of the year. 1. 1. No difference was observed in winter between hibernating animals and active animals awake for 24 hr. 2. 2. A slight increase of cholesterol/phospholipid molar ratio was observed in winter. 3. 3. A slight increase of the ratio ethanolamine phosphoglycerides/choline phosphoglycerides was observed in summer and autumn. 4. 4. Some changes in sugar moieties proportions of gangliosides were observed with a tendency of increased polysialylation in winter. 5. 5. An increase of docosahexaenoic acid was observed in summer, while a slight increase of linoleic acid and of the monounsaturated fatty acids was observed in winter. These changes were mainly exhibited in the synaptosomal fraction. All the changes observed were of very small magnitude and might not be sufficient for the maintenance of a fluid state of membranes during hibernation.