The sizes of the exchangeable pools of selenium in elderly women and their relation to institutionalization

Exchangeable pools of Se after an intravenous injection of 74Se-enriched isotope as sodium selenite were measured in two groups (n 9) of elderly women (free-living aged 64-82 years and institutionalized aged 68-82 years), and a comparison group (n 9) of young women aged 31-40 years to evaluate the effect of age and institutionalization on Se reserves. Dietary Se intake was not different among the three groups. Plasma Se and glutathione peroxidase (EC 1.11.1.9) levels were significantly lower in the institutionalized elderly women (P < 0.05). In each of the three groups, two pools were determined from our model. The size of the first pool and the sum of the two pools were lower in the group of institutionalized elderly women than in the other two groups. The significant correlation between plasma Se level and total Se pool size (r 0.66, P < 0.01) indicated that this last variable could serve as a new marker of Se status. Finally, these data suggest that the Se status of elderly women is more related to lifestyle, in terms of institutionalization or not, than to age per s

DYRK1A, a Novel Determinant of the Methionine-Homocysteine Cycle in Different Mouse Models Overexpressing this Down-Syndrome-Associated Kinase

BACKGROUND:Hyperhomocysteinemia, characterized by increased plasma homocysteine level, is associated with an increased risk of atherosclerosis. On the contrary, patients with Down syndrome appear to be protected from the development of atherosclerosis. We previously found a deleterious effect of hyperhomocysteinemia on expression of DYRK1A, a Down-syndrome-associated kinase. As increased expression of DYRK1A and low plasma homocysteine level have been associated with Down syndrome, we aimed to analyze the effect of its over-expression on homocysteine metabolism in mice. METHODOLOGY/PRINCIPAL FINDINGS:Effects of DYRK1A over-expression were examined by biochemical analysis of methionine metabolites, real-time quantitative reverse-transcription polymerase chain reaction, and enzyme activities. We found that over-expression of Dyrk1a increased the hepatic NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase activities, concomitant with decreased level of plasma homocysteine in three mice models overexpressing Dyrk1a. Moreover, these effects were abolished by treatment with harmine, the most potent and specific inhibitor of Dyrk1a. The increased NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase activities were also found in lymphoblastoid cell lines from patients with Down syndrome. CONCLUSIONS/SIGNIFICANCE:Our results might give clues to understand the protective effect of Down syndrome against vascular defect through a decrease of homocysteine level by DYRK1A over-expression. They reveal a link between the Dyrk1a signaling pathway and the homocysteine cycle

[The SFBC scientific workgroups].

International audienceEditoria

Hyperhomocysteinaemia is associated with osteoporosis in patients with Crohn's disease.

International audienceBACKGROUND: A high prevalence of osteoporosis is observed in Crohn's disease. Recent data have shown that homocysteinaemia is an important risk factor in low-bone mineralization and fracture. AIM: To look for an association between homocysteinaemia and low-bone mineralization in Crohn's disease patients. PATIENTS AND METHODS: Ninety-two consecutive patients (sex ratio M/F 0.87; mean age: 36.6 +/- 13.2 years) were recruited between 2003 and 2005. Bone densitometry was performed on inclusion. The following parameters were analysed: age, sex, Crohn's Disease Activity Index, duration and extent of Crohn's disease, smoking status, corticosteroid treatment, immunosuppressive drugs, plasma homocysteine, folate and vitamin B12 concentration. RESULTS: The prevalence of a high homocysteine level (>15 micromol/L) was 60%. Osteoporosis and low-bone mineralization observed in 26 (28%), and 60 (65%) patients, respectively. On a multivariate analysis, associated factors for osteoporosis and low-bone mineralization were respectively: hyperhomocysteinaemia (OR: 61.4; CI: 95: 23-250; P < 0.001), and ileal Crohn's disease [OR: 13.8; CI: 95: 2.5-150; P = 0.036] for osteoporosis and hyperhomocysteinaemia [OR: 63.7; CI: 95: 8.5-250; P < 0.001] and disease duration of at least 5 years [OR: 11.4; CI: 95: 1.31-99; P = 0.039] for low-bone mineralization. Results were similar whichever site osteoporosis was detected. CONCLUSION: Hyperhomocysteinaemia was observed in 60% of our Crohn's disease patients and was strongly associated with low-bone mineralization and osteoporosis (OR: 61.4)

Cross-sectional association between homocysteine and motor function in the elderly.

International audienceOBJECTIVE: To determine if there is a cross-sectional association between homocysteine (tHcy) level and measures of gait and balance in elderly subjects. METHODS: We studied 3,609 noninstitutionalized subjects aged 65 to 85 years from the Dijon (France) center of the Three-City Study. tHcy concentration was measured from fasting blood samples. Motor function was assessed by measuring walking speed and by using a modified version of the Tinetti scale. RESULTS: After adjustment for confounders, mean maximum walking speed (MWS) decreased with increasing tHcy levels (p = 0.001). The odds ratio (OR) (95% CI) for having a MWS below the 40th percentile was 1.9 (1.4 to 2.5) in subjects with tHcy levels in the upper quintile compared with those in the lowest quintile. Compared with subjects in the lowest tHcy quintile, the OR for having a modified Tinetti score below 16 ranged from 1.0 (0.8 to 1.4) in the second quintile to 1.9 (1.3 to 2.6) in the upper quintile (p < 0.0001). CONCLUSIONS: Elevated homocysteine concentrations are associated with worse motor performances in the elderly. These findings support the hypothesis of a vascular contribution to motor function

Plasma carotenoids and retinol and overall and breast cancer risk: A nested case-control study

International audienceExperimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU. VI. MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/ case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 mu mol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma beta-carotene (ORD 0.95, 95% CID 0.90-0.99, P-trend= 0.04) and beta-cryptoxanthin concentrations (OR D 0.89, 95% CI D 0.81-0.99, P-trend = 0.03) were inversely associated with overall cancer risk. Plasma beta-cryptoxanthin concentration was inversely associated with breast cancer risk (OR D 0.83, 95% CI D 0.71-0.96, P-trend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99-1.15), P-trend = 0.06. This association turned significant (P-trend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of beta-cryptoxanthin and both overall and breast cancer risk, and an inverse association between beta-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation

Dietary selenium intake affects cardiac susceptibility to ischaemia/reperfusion in male senescent rats.

International audienceBACKGROUND: cardiovascular ageing is associated with an increase in cardiac susceptibility to ischaemia and reperfusion. This has been suggested to be partly related to an increased sensitivity of the myocardium to the reactive oxygen species that are produced during post-ischaemic reperfusion. The aim of the present study was therefore to determine whether increasing cardiac glutathione peroxidase activity by a selenium-enriched diet could afford some protection against ischaemia and reperfusion to senescent rat hearts. METHODS: 22 months old male Wistar rats received either a high-selenium (1.5 mg Se/kg diet) or a low-selenium (0.05 mg Se/kg diet) diet for 10 weeks. At the end of the diet, hearts were submitted to ischaemia and reperfusion ex vivo and either fixed for semi-quantitative analysis of ultrastructural damage by electron microscopy or used for glutathione peroxidase activity assessment. RESULTS: high-selenium supply increased cardiac total, mitochondrial and cytosolic glutathione peroxidase activities. Moreover, this diet induced a significant improvement of cardiac post-ischaemic functional recovery. Finally, this preservation of cardiac function was associated with a significant limitation of ultrastructural alterations of sarcomeres and mitochondria. CONCLUSION: our high-selenium diet considerably limits the sensitivity of senescent rat hearts to ischaemia and reperfusion. This finding suggests that peroxides might play a key role in the increase in cardiac sensitivity to ischaemia and reperfusion during ageing. Together with the observation that selenium status decreases with age in humans, our results indicate that reinforcing selenium supply could improve the prognosis of cardiovascular diseases in old patients

Determination of dansylated polyamines in red blood cells by liquid chromatography-tandem mass spectrometry.

International audienceThe concentration of polyamines in red blood cells (RBCs) is considered to be an index of cell proliferation. This index has been demonstrated to be of clinical importance for the follow-up and treatment of some cancer patients. The concentration of polyamines in RBCs is usually determined by high-performance liquid chromatography (HPLC) with fluorescence detection. In the current work, we present a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of putrescine, spermidine, and spermine, the three major polyamines in RBCs. The polyamines were dansylated and analyzed by an LC gradient of 20-min duration on a C18 column on-line with a tandem mass spectrometer. An internal standard (1,8-diaminooctane) was used for quantification. This method exhibited excellent linearity for the three polyamines with regression coefficients higher than 0.99. The limits of detection for putrescine, spermidine, and spermine were 0.10, 0.75, and 0.50 pmol/ml, respectively. The intrarun precision values for putrescine, spermidine, and spermine all were better than 10%, and the interrun precision values were 13%, 9%, and 20%, respectively. The LC-MS/MS method is sufficiently simple and reliable enough to replace the currently used HPLC method with fluorescence detection in which putrescine is not always detectable

Carotenoid-rich dietary patterns during midlife and subsequent cognitive function

International audienceCarotenoids may help to prevent the ageing of the brain. Previous findings regarding beta-carotene alone are not consistent. In the present study, we evaluated the cross-time association between a carotenoid-rich dietary pattern (CDP) and subsequent cognitive performance using a sample of 2983 middle-aged adults participating in the SU.VI.MAX (Supplementation en Vitamines et Mineraux Antioxydants) study. Cognitive performance was assessed in 2007-9 using six neuropsychological tests, and a composite cognitive score was computed. The cognitive data were related to dietary data obtained by repeated 24 h dietary records (1994-6) and to measurements of baseline plasma concentrations of carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene and cis-beta-carotene). DP were extracted using the reduced rank regression method for 381 participants and then extrapolated to the whole sample using plasma carotenoid concentrations as response variables. Associations between a CDP and cognitive function measured 13 years later were estimated with ANCOVA providing mean difference values and 95% CI across the tertiles of CDP. A correlation between CDP and consumption of orange-and green-coloured fruits and vegetables, vegetable oils and soup was observed. CDP was found to be associated with a higher composite cognitive score (mean difference 1.04, 95% CI 0.20, 1.87, P for trend 0.02), after adjustment for sociodemographic, lifestyle and health factors. Similar findings were obtained for scores obtained in the cued recall task, backward digit span task, trail making test and semantic fluency task (all P for trend,0.05). Further studies ought to confirm whether a diet providing sufficient quantity and variety of coloured fruits and vegetables may contribute to the preservation of cognitive function during ageing