“
“BACKGROUND: Bronchopulmonary dysplasia is an inflammatory lung disease that afflicts preterm infants requiring supplemental oxygen and is associated with impaired pulmonary angiogenesis. We tested the hypothesis that there is a critical threshold of inspired O-2 (FiO(2)) that alters pulmonary angiogenesis.\n\nMETHODS: Within 2-6h of birth, rat pups were exposed to 10%, 21%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% FiO(2) for 2h. Mixed

arterial venous blood gases, serum and pulmonary levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1, and pulmonary angiogenesis gene profiles were determined.\n\nRESULTS: Po-2 increased with hyperoxia from 35.6 +/- 5.0 (range: 31.5-39.8) Rabusertib at 10% O-2 to 108.5 +/- 25.0 (range: 82.2-134.8) at 100% O-2. Po-2 at 21% O-2 was 42.4 +/- 7.3 (range: 36.8-48.1). Lung VEGF levels declined at 40%-100%. The critical Po-2 associated with

decreased lung VEGF was 66 mm Hg, achieved with a FiO(2) of 0.4. Po-2 was inversely correlated with VEGF levels in the lungs (R = 0.377; P < 0.008). Antiangiogenesis genes were robustly upregulated at 70%, predominantly in males. Data are reported as mean +/- SD.\n\nCONCLUSIONS: A critical threshold of FiO(2) affecting angiogenesis exists in immature lungs. Exposure of preterm lungs to >40% inspired NVP-HSP990 O-2, even for 2 h, may result in abnormal expression of biomarkers regulating lung angiogenesis.”
“BACKGROUND: A recent meta-analysis based on data from

> 7,000 pregnancies reported an -association between prenatal polychlorinated biphenyl (PCB)-153 exposure and reduced birth weight. Gestational weight gain, which is associated negatively with PCB levels in maternal and cord blood, and positively with birth weight, could substantially confound this association.\n\nOBJECTIVE: We sought to estimate the influence of gestational weight gain on the association between PCB-153 exposure and birth weight using a pharmacokinetic JNJ-26481585 model.\n\nMETHODS: We modified a recently published pharmacokinetic model and ran Monte Carlo simulations accounting for variability in physiologic parameters and their correlations. We evaluated the pharmacokinetic model by comparing simulated plasma PCB-153 levels during pregnancy to serial measurements in 10 pregnant women from another study population. We estimated the association between simulated plasma PCB-153 levels and birth weight using linear regression models.\n\nRESULTS: The plasma PCB-153 level profiles generated with the pharmacokinetic model were comparable to measured levels in 10 pregnant women. We estimated a 118-g decrease in birth weight (95% CI: -129, -106 g) for each 1-mu g/L increase in simulated cord plasma PCB-153, compared with the 150-g decrease estimated based on the previous meta-analysis.