Pediatric research
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The purpose of this study was to determine whether mild hypothermia after a moderate hypoxic-ischemic insult reduces the extent of brain damage. Hypoxia was achieved in newborn piglets (n = 24; age, 14-72 h) by abrupt reduction of the inspired oxygen concentration (FiO2) to the maximum concentration (approximately 6%) giving low amplitude (< 7.0 microV) EEG. FiO2 was temporarily increased if heart rate, blood pressure, or end expiratory partial pressure of alveolar CO2 (PAco2) were markedly reduced. ⋯ It was concluded that there was no general beneficial effect of postinsult hypothermia. However, when controlling for the duration of the insult and occurrence of seizures, hypothermia reduced the severity of brain damage. This indicates a significant neuroprotective effect of 3 h of mild hypothermia on moderate, but not severe, hypoxic-ischemic insults.
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The aim of this study was to produce a neonatal piglet model which, avoiding vessel ligation, exposed the whole animal to hypoxia and produced dose-dependent clinical encephalopathy and neuropathologic damage similar to that seen after birth asphyxia. Twenty-three piglets were halothane-anesthetized. Hypoxia was induced in 19 piglets by reducing the fractional concentration of inspired oxygen (FiO2) to the maximum concentration at which the EEG amplitude was below 7 microV (low amplitude) for 17-55 min. ⋯ We conclude that EEG-controlled hypoxia and subsequent intensive care enabled the animals to survive with an encephalopathy which correlated with the cerebral hypoxic insult. The encephalopathy was clinically, electrophysiologically, and neuropathologically similar to that in the asphyxiated term infant. This model is suitable for examining mechanisms of damage and evaluation of potential protective therapies after birth asphyxia.
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Because the antiprotease defense in cystic fibrosis (CF) airways is overwhelmed by neutrophil elastase (NE), substitution of antiproteases such as secretory leukoprotease inhibitor (SLPI) seems to be a reasonable therapeutic approach. Knowing, however, that native antiproteases may be liable to rapid inactivation by the locally abundant oxidants, we comparatively investigated the interactions of CF sputum with recombinant native SLPI (rSLPI) and its partially oxidation-resistant variant (rSLPI-242), respectively, to estimate their therapeutic potentials. NE activity in supernatants from diluted CF sputum samples was dose-dependently inhibited by both rSLPI and rSLPI-242, with comparable potency. ⋯ Furthermore, secretion of radiolabeled macromolecules from porcine tracheal glands induced by purified NE or by CF sputum was inhibited dose-dependently by rSLPI and even better by rSLPI-242. We conclude that both rSLPI and rSLPI-242 effectively inhibit NE activity and NE-induced gland hypersecretion in vitro. In vivo effects of CF remain to be analyzed; an advantage of the partially oxidation-resistant rSLPI-242 can be expected.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Serum cortisol, dehydroepiandrosterone sulfate, and steroid-binding globulins in preterm neonates: effect of gestational age and dexamethasone therapy.
Our aim was to assess adrenocortical function in very low birth weight infants, specifically to evaluate the impact of gestational age and dexamethasone (DEX) therapy on serum concentrations of total and free cortisol, dehydroepiandrosterone sulfate (DHEAS), and steroid-binding globulins. Twelve moderately preterm or full-term neonates of 38 +/- 4 (mean +/- SD) wk of gestation and 36 ill preterm neonates of 26 +/- 2 (mean +/- SD) wk of gestation were studied. Twenty-three of the 36 ill preterm neonates participated in a randomized neonatal DEX trial for the treatment of early chronic lung disease and received a 1-wk treatment of DEX or placebo. ⋯ One week after discontinuation of DEX or placebo, basal cortisol concentrations did not differ significantly, but ACTH-stimulated cortisol levels were lower in the DEX-treated than in the placebo-treated infants. DEX therapy decreased the serum CBG and DHEAS concentrations and caused a transient suppression in the adrenocortical function. Despite severe illness, the very preterm neonates had relatively low basal cortisol concentrations, suggesting their reduced ability to respond adequately to stress during intensive care.
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Low dose ATP-MgCl2 is reported to cause selective pulmonary vasodilation during hypoxic and thromboxane mimetic-induced constriction. In addition, it has been shown to increase cardiac output and improve cellular function during circulatory shock. Based on these properties we hypothesized that ATP-MgCl2 might ameliorate the cardiopulmonary manifestations of sepsis secondary to group B streptococci (GBS). ⋯ Also dynamic lung compliance was higher (p < 0.001) and pulmonary airway resistance lower (p < 0.001) in treated animals. Median survival in control animals was 153 min, whereas all treated animals survived to 240 min (p < 0.001). These data demonstrate that ATP-MgCl2 ameliorates the deleterious cardiopulmonary manifestations of GBS sepsis and results in improved survival in a young animal model.