• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.56-66
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• 2003

Purpose : Human umbilical vein endothelial cells(HUVECs) play an important role in regulating blood flow by releasing vasoactive substances. It has been reported that endothelial impairment and dysfunction might be a primary cause of placental vascular disease, which is manifested clinically as preeclampsia in mother and intrauterine growth restriction in fetus. Furthermore, the frequency of apoptotic changes is increased in umbilical and placental tissues from growth-restricted pregnancies. However, the various mechanisms of umbilical endothelial cell apoptosis have not been broadly proposed. We investigate the effects of amiloride derivatives on apoptotic death of HUVECs and identify their ionic mechanism. Methods : HUVECs were purchased from Clonetics, and cultured on endothelial cell growth medium. MTT assay and flow cytometry were used for assessing cytotoxic effect and confirming the apoptosis. Changes in intracellular ion concentrations were measured with specific fluorescent dyes and fluorescence imaging analysis system. Results : Amiloride derivatives elicited cytotoxic effects on HUVECs with dose-dependent manners and the rank order of potency is HMA($IC_{50}\;11.2{\mu}M$), MIA>EIPA>>amiloride. HMA-induced cytotoxicity is dependent on extra- and intracellular pH, that is, increase extra- and intracellular pH augmented the cytotoxic effects of HMA. HMA dose-dependently reduced intracellular major ions, such as $K^+$ and $Cl^-$. Interestingly, the depletion of intracellular ions induced by HMA was also significantly enhanced at alkaline extracellular pH. Conclusion : Amiloride derivatives induce apoptosis of HUVECs with dose and pH dependent manners. They reduce intracellular $K^+$ and $Cl^-$ concentration, which is also extracellular pH dependent.

• Neonatal Medicine
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• v.17 no.1
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• pp.21-33
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• 2010

Purpose : The increased survival of preterm infants in the neonatal intensive care unit recently has resulted in an increased frequency of bronchopulmonary dysplasia (BPD), especially with atypical forms. However, there have been few studies compairing classic and atypical BPD. The aim of this study was to investigate the differences between these two types of BPD. Methods : Infants with a gestational age less than 32 weeks born at the Seoul National University Hospital and Bundang Seoul National University Hospital from May 2004 to April 2007 were included. The data were categorized in 2 groups, classic and atypical BPD. We determined the incidence of BPD, and compared perinatal factors and postnatal managements between two groups. Results : Among 260 study subjects, 141 (54.2%) infants had BPD. Classic BPD infants were 64 and atypical BPD infants were 77. Comparison of differences between 2 groups, classic BPD infants were associated with respiratory distress syndrome, patent ductus arteriosus, intrauterine growth restriction, more high-frequency ventilator (HFV) use, low 1 and 5 minute Apgar scores. Atypical BPD infants were associated with antenatal steroid use, maternal premature rupture of membrane and chorioamnionitis (CAM). In multivariate analysis, more HFV use was associated with classic BPD. Antenatal steroid use, clinical CAM and histological CAM were associated with atypical BPD. Conclusion : The results of this study showed that antenatal factors (antenatal steroid use, clinical CAM, histological CAM) were associated with atypical BPD and postnatal factors (HFV used more) were associated with classic BPD. Further studies are needed for prevention and treatment of BPD.