Supplemental oxygen, used to treat pulmonary insufficiency in newborns, contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome P4501A enzymes are induced by hyperoxia in animal models, but their role in human systems is unknown. Here we investigated the molecular mechanisms of induction of CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were exposed to hyperoxia (95% O 2 ) for 0-72 hours, and CYP1A1 activities, apoprotein contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1 activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction assays showed attenuation of cell injury with the CYP1A1 inducer betanaphthoflavone (BNF). Our results strongly suggest that hyperoxia transcriptionally activates CYP1A1 expression in human lung cell lines by AHR-dependent mechanisms, and that CYP1A1 induction is associated with decreased toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous AHR ligands could lead to novel interventions in the treatment of BPD.

The cDNA for the fifth mammalian aquaporin (AQP5) was isolated from rat, and expression was demonstrated in rat salivary and lacrimal glands, cornea, and lung (Raina, S., Preston, G. M., Guggino, W. B., and Agre, P.

Terminal deletions of chromosome 15q are rare events, with only six cases previously described. Here we describe a seventh case of a terminal deletion of the long arm of chromosome 15, with the present case exhibiting clinical features not previously described.

Background: Recent studies reported conflicting results on the relationship between antenatal magnesium sulfate (MgSO₄) exposure and neonatal intestinal injury. Most studies have not assessed MgSO₄ exposure quantitatively and none reported the exposure timing. Objectives: The aim of this work was to assess whether there is a temporal or dose-dependent relationship between antenatal MgSO₄ exposure and intestinal injury in extremely preterm neonates. Methods: A retrospective study was made of inborn neonates with gestational age ≤28 weeks and/or birth weights ≤1,000 g. Primary outcomes included necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), and/or death prior to discharge or in the first 2 weeks of life. Outcome comparisons were made based on the timing of MgSO₄ exposure, within 7 days (Mg7D) or within 3 days (Mg3D) of birth. Total cumulative doses for the Mg3D group were also computed. Results: A total of 302 neonates were included, 210 in the Mg7D group, out of whom 179 (85.2%) constituted the Mg3D group. There were no differences noted when comparing MgSO₄ exposure timing and the likelihood of NEC, SIP, and/or death. This remained the same for subgroup analysis of neonates < 26 weeks’ gestation. Each 10-g increase in MgSO₄ cumulative dose correlated with a decrease in SIP/NEC/death by 18.9% prior to discharge and by 21.9% in the first 2 weeks of life. Small for gestational age (SGA) was a potential effect modifier by a likelihood ratio test with p = 0.07. Conclusions: Antenatal MgSO₄ exposure in extremely preterm neonates was not associated with an increased risk of intestinal injury or death, and might have reduced these complications in a dose-dependent manner in our study. This protective effect was more noticeable in SGA neonates.