Pediatric research
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Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride (CoCl2) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury in neonatal rat brain. We examined long-term functional and protective actions of preconditioning induced by hypoxia, CoCl(2) and DFX in a neonatal rat model of HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8% oxygen) or injections of CoCl(2), DFX or saline vehicle and 24 h later rats underwent HI or sham surgery. ⋯ HI increased the number of foot faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder test. Only preconditioning with hypoxia reversed all three functional deficits after HI. These findings indicate that preconditioning, especially when induced by hypoxia, has the potential to minimize the morphologic and functional effects of neonatal HI injury.
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Literature suggests that glucocorticoid (GC) exposure during early life may have long-term consequences into adult life. GCs are known to influence hepatic bile acid synthesis and their transport within the enterohepatic circulation. This study addresses effects of early postnatal exposure to GC on hepatic expression of key genes in bile acid metabolism and bile acid kinetics in adult rats. ⋯ DEX acutely induced hepatic mRNA levels of cholesterol 7alpha-hydroxylase (Cyp7a1), cholesterol 27-hydroxylase (Cyp27), and in particular sterol 12alpha-hydroxylase (Cyp8b1), whereas expression of the bile acid transporters bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) was moderately affected. Neonatal DEX administration led to increased bilary lipid secretion, decreased Cyp8B1 mRNA expression and a 3-fold higher Cyp7a1/Cyp8b1 mRNA ratio in rats at week 8 compared with age-matched controls without alterations in bile acid kinetics. Therefore, neonatal DEX administration causes altered gene expressions later in life that are not translated into quantitative changes in bile acid kinetics.
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The genetic mechanisms underlying the regulation of adrenarche are unknown. The aim of the study was to find out whether ACTH receptor (MC2R) promoter polymorphism associates with premature adrenarche (PA) and its characteristics. DNA samples of 74 prepubertal children with PA and their age- and gender-matched 97 healthy controls were genotyped for the -2 bp T/C diallelic MC2R promoter polymorphism (MC2R -2 T>C) All children were examined clinically, and hormonal measurements after an overnight fast and a low-dose ACTH stimulation test were performed. ⋯ The frequency of the MC2R -2 T>C polymorphism was significantly higher in PA children with premature pubarche than in those with milder signs of PA or in control children (p = 0.04). In children with PA, the polymorphism associated with higher baseline serum dehydroepiandrosterone (p = 0.03), androstenedione (p = 0.02), plasma ACTH (p = 0.03) levels and with lower birth weight (p = 0.02). Our study provides evidence that the MC2R promoter polymorphism modulates the hypothalamo-pituitary-adrenal axis in children and may play a role in altered regulation of adrenarche.
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To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of l-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. ⋯ Exogenous Gln decreased muscle free Glu and Gln + Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln + Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.
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Multicenter Study
Post-exercise airway narrowing in healthy primary school children.
Changes in lung function after exercise in healthy primary school children have mostly been described in field studies. More complete description and insight into relevant mechanisms may be provided in lung function laboratory. The aim was to describe airway caliber and response to deep inhalation (DI) after exercise in healthy primary school children. ⋯ DI induced significant decrease in Rrs (p = 0.01) that was not different between E5 and baseline. Healthy primary school children exhibit changes in Rrs and spirometry after exercise indicating small but significant airway narrowing. The response to DI similar at baseline and E5 suggests airway narrowing from hyperemia in the bronchial wall rather than airway smooth muscle constriction.