6 research outputs found
Genome-wide association study of bronchopulmonary dysplasia: a potential role for variants near the CRP gene
Bronchopulmonary dysplasia (BPD), the main consequence of prematurity, has a significant heritability, but little is known about predisposing genes. The aim of this study was to identify gene loci predisposing infants to BPD. The initial genome-wide association study (GWAS) included 174 Finnish preterm infants of gestational age 24-30 weeks. Thereafter, the most promising single-nucleotide polymorphisms (SNPs) associated with BPD were genotyped in both Finnish (n = 555) and non-Finnish (n = 388) replication cohorts. Finally, plasma CRP levels from the first week of life and the risk of BPD were assessed. SNP rs11265269, flanking the CRP gene, showed the strongest signal in GWAS (odds ratio [ OR] 3.2, p = 3.4 x 10(-6)). This association was nominally replicated in Finnish and French African populations. A number of other SNPs in the CRP region, including rs3093059, had nominal associations with BPD. During the first week of life the elevated plasma levels of CRP predicted the risk of BPD (OR 3.4, p = 2.9 x 10(-4)) and the SNP rs3093059 associated nominally with plasma CRP levels. Finally, SNP rs11265269 was identified as a risk factor of BPD (OR 1.8, p = 5.3 x 10(-5)), independently of the robust antenatal risk factors. As such, in BPD, a potential role for variants near CRP gene is proposed
Impaired early neurologic outcome in newborn piglets reoxygenated with 100% oxygen compared with room air after pneumothorax-induced asphyxia
Birth asphyxia is a serious problem worldwide, resulting in 1 million deaths and
an equal number of neurologic sequelae annually. It is therefore important to
develop new and better ways to treat asphyxia. In the present study we tested the
effects of reoxygenation with room air or with 100% oxygen (O2) after
experimental pneumothorax-induced asphyxia on the blood oxidative stress
indicators, early neurologic outcome, and cerebral histopathology of newborn
piglets. Twenty-six animals were studied in three experimental groups: 1)
sham-operated animals (SHAM, n = 6), 2) animals reoxygenated with room air after
pneumothorax (R21, n = 10), and 3) animals reoxygenated with 100% O2 after
pneumothorax (R100, n = 10). In groups R21 and R100, asphyxia was induced under
anesthesia with bilateral intrapleural room air insufflation. Gasping,
bradyarrhythmia, arterial hypotension, hypoxemia, hypercarbia, and combined
acidosis occurred 62 +/- 6 min (R21) or 65 +/- 7 min (R100; mean +/- SD) after
the start of the experiments; then pneumothorax was relieved, and a 10-min
reoxygenation period was started with mechanical ventilation with room air (R21)
or with 100% O2 (R100). The newborn piglets then breathed room air spontaneously
during the next 3 h. Blood oxidative stress indicators (oxidized and reduced
glutathione, plasma Hb, and malondialdehyde concentrations) were measured at
different stages of the experiments. Early neurologic outcome examinations
(neurologic score of 20 indicates normal, 5 indicates brain-dead) were performed
at the end of the study. The brains were next fixed, and various regions were
stained for cerebral histopathology. In the SHAM group, the blood gas and
acid-base status differed significantly from those measured in groups R21 and
R100. In group R100, arterial PO2 was significantly higher after 5 (13.8 +/- 5.6
kPa) and 10 min (13.2 +/- 6.3 kPa) of reoxygenation than in group R21 (8.7 +/-
2.8 kPa and 9.2 +/- 3.1 kPa). The levels of all oxidative stress indicators
remained unchanged in the study groups (SHAM, R21, and R100). The neurologic
examination score in the SHAM group was 18 +/- 0, in group R21 it was 13.5 +/-
3.1, and in group R100 it was 9.5 +/- 4.1 (significant differences between SHAM
and R21 or R100, and between R21 and R100). Cerebral histopathology revealed
marked damage of similar severity in both asphyxiated groups. We conclude that
the blood oxidative stress indicators and cerebral histopathology did not differ
significantly after a 10-min period of reoxygenation with room air or with 100%
O2 after pneumothorax-induced asphyxia, but reoxygenation with 100% O2 might
impair the early neurologic outcome of newborn piglets