ABSTRACT
RATIONALE: Respiratory Distress Syndrome (RDS) due to prematurity is one of the most important causes of morbidity and mortality in Neonatal Intensive Care Units. According to few studies in recent years, endothelial nitric oxide synthase (eNOS) gene polymorphisms are found to be partially responsible for liability to RDS. The purpose of this study was to determine the association between eNOS gene polymorphism and RDS in preterm neonates. PATIENTS AND METHODS: The patient group consisted of 152 premature neonates born before 37 weeks of gestation and diagnosed as RDS. The control group consisted of 125 premature neonates born before 37 weeks of gestation, but was not diagnosed as RDS. Genomic DNA from patients and controls was analyzed by polymerase chain reaction. RESULTS: It was found that Glu/Glu, Glu/Asp, and Asp/Asp genotype frequencies of the eNOS gene polymorphism were 35.2%, 59.2%, and 5.6% of the control group, and 32.9%, 65.1%, and 2.0% of the patient group, respectively (P > 0.05). However, significant increases in Glu/Glu genotype and Glu allele frequencies were noted in the RDS groups when the preterm neonates were divided into two groups (24-30 weeks and 31-36 weeks) by gestational age. Additionally, Glu/Asp genotype and Asp allele were markedly less frequent among the RDS groups (P < 0.05). Asp allele frequency in boys and Glu allele frequency in girls were significantly high in RDS group (P < 0.05). CONCLUSIONS: These data suggest that there were significant gestational age-related differences between RDS and control groups in terms of Glu298Asp polymorphism. Therefore, RDS seems to develop with alterations in eNOS Glu298Asp genotype frequencies in the Turkish population.
Subject(s)
Nitric Oxide Synthase Type III/genetics , Polymorphism, Genetic , Respiratory Distress Syndrome, Newborn/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Infant, Newborn , Infant, Premature , Male , Polymerase Chain Reaction , TurkeyABSTRACT
BACKGROUND/PURPOSE: Necrotizing enterocolitis (NEC) is a major cause of mortality in neonates and is associated with a disruption in the protective intestinal barrier. The precise cause of NEC is elusive. However, ischemia/reperfusion injury of the intestine has been considered a major contributing factor. We examined the role of Y-27632, a selective Rho-kinase inhibitor, on a hypoxia/reoxygenation (H/R)-induced intestinal injury of newborn rat pups. METHODS: Hypoxia/reoxygenation was achieved by placing rat pups in an airtight chamber aerated with 95% N(2) + 5% CO(2) for 10 minutes followed by 10-minute 100% oxygen. Forty newborn rat pups were randomly allocated into 4 groups. Group 1 served as untreated controls. The pups in group 2 were subjected to H/R only. In groups 3 and 4, the rats were treated with intraperitoneal injection of 0.3 and 3 mg kg(-1) day(-1) of Y-27632 for 5 days following H/R, respectively. The pups were killed 6 days following the H/R injury. Intestine specimens were evaluated for histopathology and biochemical investigation. RESULTS: The microscopic lesions in H/R rat pups were virtually the same as those seen in neonatal NEC, with severe destruction of villi and crypts. Hypoxia/reoxygenation resulted in significant elevation in malondialdehyde levels, but decreased tissue nitric oxide levels (P < .05). Protective effects of Y-27632 on H/R-induced intestinal injury of newborn rat pups were observed with a significant decrease in the intestinal injury score, suppression in malondialdehyde levels, and increase in nitric oxide levels (P < .05). CONCLUSIONS: In this experimental study, Y-27632 significantly attenuated H/R-induced intestinal injury. These findings indicate that inhibition of Rho-kinase may offer a novel therapeutic approach in the treatment of NEC.
