Glutathione reductase is essential for host defense against bacterial infection.

Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, a major cellular antioxidant. We have recently shown that Gsr is essential for host defense against the gram-negative bacteria Escherichia coli in a mouse model of sepsis. Although we have demonstrated that Gsr is required for sustaining the oxidative burst and the development of neutrophil extracellular traps, the role of Gsr in other phagocytic functions remains unclear. It is also unclear whether Gsr-deficient mice exhibit host defense defects against gram-positive bacteria. In this study, we characterized the effects of Gsr deficiency on the innate immune responses to a gram-positive bacterium, group B Streptococcus, and to the gram-negative bacterial cell wall component lipopolysaccharide (LPS). We found that, like E. coli, group B Streptococcus resulted in a substantially more robust cytokine response and a markedly higher morbidity and mortality in Gsr-deficient mice than in wild-type mice. The increased morbidity and mortality were associated with greater bacterial burden in the Gsr-deficient mice. Interestingly, Gsr-deficient mice did not exhibit a greater sensitivity to LPS than did wild-type mice. Analysis of the neutrophils of Gsr-deficient mice revealed impaired phagocytosis. In response to thioglycollate stimulation, Gsr-deficient mice mobilized far fewer phagocytes, including neutrophils, macrophages, and eosinophils, into their peritoneal cavities than did wild-type mice. The defective phagocyte mobilization is associated with profound oxidation and aggregation of ascitic proteins, particularly albumin. Our results indicate that the oxidative defense mechanism mediated by Gsr is required for an effective innate immune response against bacteria, probably by preventing phagocyte dysfunction due to oxidative damage.

Changes in dynamic insulin and gastrointestinal hormone secretion in obese children.

BACKGROUND: Disturbed satiety and hunger perception in obese individuals has been reported, however data on the dynamic changes of hormonal mediators are sparse. OBJECTIVE: To evaluate the secretion pattern of insulin, ghrelin, peptide-YY (PYY), and amylin via 0 to 180 min oral glucose tolerance testing in obese and lean children. SUBJECTS AND METHODS: A prospective clinical study was conducted on lean (n=9) and obese (n=20) Caucasian children of comparable age, gender, and pubertal stage. Serial blood samples were collected. RESULTS: Compared to baseline, levels of acylated ghrelin showed a significant decrease in lean (p<0.05) but not in obese children. PYY increase was blunted and of shorter duration (60 min) in obese children. Amylin levels increased in both groups, and attained significantly higher levels in obese children (p<0.05). CONCLUSION: Glucose stimulated gut hormone secretion differed between obese and lean children, and may explain the disturbed satiety observed in obese children.

Neonatal growth rate and development of mice raised on milk transgenically enriched with omega-3 fatty acids.

The n-3 polyunsaturated fatty acid (PUFA) status of the neonatal brain has been associated with cognitive capability in mice. Previously, transgenic mice expressing the Caenorhabditis elegans (C. elegans) n-3 fatty acid (FA) desaturase gene under the control of a lactation-induced mammary gland promoter were found to produce milk containing significantly elevated levels of alpha-linolenic (ALA) and eicosapentaenoic (EPA) acid. In this study, the preweaning growth rate and development of mouse pups consuming elevated n-3 PUFA milk produced by transgenic dams were evaluated using the Wahlsten observational test battery and the object novelty preference test. Brains were collected at weaning and analyzed for FA composition. Pups nursed on transgenic dams had earlier eye opening, higher visual placement scores, and 1.6-fold more docosahexaenoic acid (DHA) in their brains compared with pups raised on wildtype dams. There was no significant effect of milk treatment (transgenic versus control) on other developmental parameters or novelty preference behavior. The pups consuming the elevated n-3 PUFA transgenic milk had slower preweaning growth rates such that pups reared on wildtype dams producing control milk were heavier than pups reared on transgenic dams producing high n-3 PUFA milk by postnatal day 18. This transgenic model enables the provision of a high n-3 PUFA lactational environment independent of maternal diet or gestational FA status.