AAA (abdominal aortic aneurysm) is an important cause of sudden death in older adults, but there is no current effective drug therapy for this disease. The UCNs (urocortins1-3) and their receptors: CRFR (corticotrophin-releasing factor receptor)-1 and -2 have been implicated in various CVDs (cardiovascular diseases). We assessed the relative expression of UCN1-3 in AAA by qRT-PCR (quantitative reverse transcription-PCR) and ELISA, and examined in vitro how UCN2 affects human aortic VSMC (vascular smooth muscle cell) Akt phosphorylation, pro-inflammatory cytokine IL (interleukin)-6 secretion, proliferation, cell cycle and apoptosis. UCN2 and CRFR2 expression were significantly up-regulated in biopsies from the AAA body. AAA body biopsies released high amounts of UCN2 in vitro. Median plasma UCN2 concentrations were 2.20 ng/ml (interquartile range 1.14-4.55 ng/ml, n=67) in AAA patients and 1.11 ng/ml (interquartile range 0.76-2.55 ng/ml, n=67) in patients with non-aneurysmal PAD (peripheral artery disease) (P=0.001). Patients with UCN2 in the highest quartile had a 4.12-fold (95% confidence interval, 1.37-12.40) greater prevalence of AAA independent of other risk factors, P=0.012. In vitro, UCN2 significantly inhibited VSMC Akt phosphorylation and proliferation in a dose-dependent manner. UCN2 induced VSMC G1 cell-cycle arrest and increased IL-6 secretion over 24 h. The CRFR2 antagonist astressin-2B significantly abrogated the effects of UCN2 on VSMCs. In conclusion, UCN2 is significantly associated with AAA and inhibits VSMC proliferation by inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA pathogenesis.
Steroids should be administered wherever there is any possibility of the provision of intensive care for periviable babies. Place of birth and ethnicity of mother should not unduly influence antenatal counselling.
DesignA qualitative study informed by grounded theory principles to explore the experiences of parents who had extremely preterm or babies with antenatally diagnosed life-threatening diagnoses who were cared for in a regional tertiary neonatal unit. The study was conducted when the child was old enough to be diagnosed with long-term neurodevelopmental or medical sequelae.SettingNorth Queensland is a large area in Eastern Australia of 500 000 km2, which is served by one tertiary neonatal unit.ParticipantsSeventeen families representing 21 extremely preterm babies and one baby with congenital malformations who was not expected to survive prior to delivery (but did) were interviewed using grounded theory principles. Interviews were coded and themes derived.ResultsParents who recollect their neonatal experiences from 3 to 7 years after the baby was cared for in the neonatal intensive care described negative themes of grief and loss, guilt and disempowerment. Positive enhancers of care included parental strengths, religion and culture, family supports and neonatal unit practices. Novel findings included that prior pregnancy loss and infertility formed part of the narrative for parents, and hope was engendered by religion for parents who did not usually have a religious faith.ConclusionsAn understanding of both the negative aspects of neonatal care and the positive enhancers is necessary to improve the neonatal experience for parents. Parents are able to contextualise their previous neonatal experiences within both the long-term outcome for the child and their own life history.
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