Phenylketonuric (PKU) subjects have a limited supply of selenium (Se) in their phenylalanine-restricted diet. A Se repletion (1 microgram Se/kg/day)/depletion study was conducted in PKU children to determine the effect of Se on thyroid function parameters. The initial plasma Se concentration (mean +/- SD: 0.26 +/- 0.12 mumol/L, p < 0.00003, n = 10) and glutathione peroxidase (GSH-Px) activity (140 +/- 58 U/L, p < 0.00003, n = 10) were significantly lower compared to age-matched controls. After 14 weeks of supplementation, the plasma Se concentration (mean +/- SD: 0.74 +/- 0.20 mumol/L) normalized (normal range: 0.57-1.15 mumol/L, mean +/- SD: 0.76 +/- 0.13 mumol/L, n = 32) and remained stable thereafter during repletion. Plasma GSH-Px activity reached normal values after 18 weeks of supplementation (312 +/- 57 U/L; normal range: 238-492 U/L, mean +/- SD: 345 +/- 54 U/L, n = 32) and increased significantly for up to eight weeks thereafter (332 +/- 52 U/L). Individual and mean thyroid parameters were initially normal in all cases. The mean concentrations of plasma thyroxine (T4: p < 0.025), free T4 (FT4: p < 0.01) and reverse triiodothyronine (rT3: p < 0.005) decreased to 75% of their initial value within three weeks of Se supplementation and remained stable thereafter, within a normal physiological range during selenium supplementation. They increased back to their initial values three weeks (T4: p < 0.05, FT4: p < 0.05) and six weeks (rT3: p < 0.025) respectively, after the end of the supplementation. In conclusion, Se supplementation modifies thyroid function parameters in Se-deficient PKU subjects most likely by an increase in activity of type I 5'-deiodinase (5'-DIase I).

Background The effects of docosahexaenoic acid (DHA) on cardiovascular disease are controversial and a mechanistic understanding of how this omega‐3 polyunsaturated fatty acid (ω‐3 PUFA) regulates platelet reactivity and the subsequent risk of a thrombotic event is warranted. In platelets, DHA is oxidized by 12‐lipoxygenase (12‐LOX) producing the oxidized lipids (oxylipins) 11‐HDHA and 14‐HDHA. We hypothesized that 12‐LOX DHA‐oxylipins may be involved in the beneficial effects observed in dietary supplemental treatment with ω‐3 PUFAs or DHA itself. Objectives To determine the effects of DHA, 11‐HDHA, and 14‐HDHA on platelet function and thrombus formation, and to elucidate the mechanism by which these ω‐3 PUFAs regulate platelet activation. Methods and results DHA, 11‐HDHA, and 14‐HDHA attenuated collagen‐induced human platelet aggregation, but only the oxylipins inhibited ⍺IIbβ3 activation and decreased ⍺‐granule secretion. Furthermore, treatment of whole blood with DHA and its oxylipins impaired platelet adhesion and accumulation to a collagen‐coated surface. Interestingly, thrombus formation was only diminished in mice treated with 11‐HDHA or 14‐HDHA, and mouse platelet activation was inhibited following acute treatment with these oxylipins or chronic treatment with DHA, suggesting that under physiologic conditions, the effects of DHA are mediated through its oxylipins. Finally, the protective mechanism of DHA oxylipins was shown to be mediated via activation of protein kinase A. Conclusions This study provides the first mechanistic evidence of how DHA and its 12‐LOX oxylipins inhibit platelet activity and thrombus formation. These findings support the beneficial effects of DHA as therapeutic intervention in atherothrombotic diseases.

No abstract

Type I 5'-deiodinase was recently characterized as a selenocysteine-containing enzyme in humans and other mammals. Up to now, the effect of selenium (Se) supplementation on thyroid hormone metabolism in humans has only been reported in the very peculiar nutritional environment of Central Africa, where combined severe iodine and Se deficiency occurs. In this study, a group of phenylketonuria subjects with a low selenium status, but a normal iodine intake were supplemented with selenium to investigate changes in their thyroid hormone metabolism. After 3 wk of selenium supplementation (1 microgram/kg/d), both the concentrations of the prohormone thyroxine (T4) and the metabolic inactive reverse triiodothyronine (rT3) decreased significantly. Clinically, the phenylketonuria subjects remained euthyroid before and after selenium supplementation. The individual changes of plasma Se and glutathione peroxidase activity were closely associated with individual changes of plasma T4 and rT3.

BackgroundThe World Health Assembly 2012 Polio Eradication and Endgame Strategic Plan calls for the eventual cessation of all oral polio vaccines (OPVs), to be replaced with inactivated polio vaccine (IPV); however, IPV induces less robust mucosal immunity than OPV. This study characterized household and community OPV shedding and transmission after OPV vaccination within primarily IPV-vaccinated communities.MethodsHouseholds in 3 IPV-vaccinated Mexican communities were randomized to receive 3 levels of OPV vaccination coverage (70%, 30%, or 10%). Ten stool samples were collected from all household members over 71 days. Analysis compared vaccinated subjects, household contacts of vaccinated subjects, and subjects in unvaccinated households. Logistic and Cox regression models were fitted to characterize transmission of OPV by coverage and household vaccination status.ResultsAmong 148 vaccinated children, 380 household contacts, and 1124 unvaccinated community contacts, 78%, 18%, and 7%, respectively, shed OPV. Community and household contacts showed no differences in transmission (odds ratio [OR], 0.67; 95% confidence interval [CI], .37–1.20), in shedding trajectory (OR, 0.61; 95% CI, .35–1.07), or in time to shedding (hazard ratio, 0.68; 95% CI, .39–1.19). Transmission began as quickly as 1 day after vaccination and persisted as long as 71 days after vaccination. Transmission within unvaccinated households differed significantly across vaccination coverage communities, with the 70% community experiencing the most transmissions (15%), and the 10% community experiencing the least (4%). These trends persisted over time and in the time to first shedding analyses.ConclusionsTransmission did not differ between household contacts of vaccinees and unvaccinated households. Understanding poliovirus transmission dynamics is important for postcertification control.