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PubMed ID: 20453525, Background: Mannose-binding lectin (MBL) as a component of innate immunity plays an important role in preterm infants in whom adaptive immunity is not sufficiently developed. Polymorphisms in immunoregulatory genes influence the response to infection and subsequent inflammation. Infection and inflammation have been implicated in the mechanisms responsible for many of the diseases in the preterm newborns. Objectives: The aim of the study was to investigate the relationship between MBL gene polymorphism and early neonatal outcome in preterm infants. Methods: Codon 54 and 57 polymorphisms in MBL2 gene were genotyped in 99 preterm infants admitted to the Neonatal Intensive Care Unit at Ege University Children's Hospital. Results: Overall frequencies of sepsis and early-onset sepsis were higher in the group of infants with MBL polymorphism when compared to infants with wild-type MBL genotype (p = 0.008, 0.009, respectively). Maximum Tollner sepsis score in the first 3 days of life was higher for the infants with variant MBL genotype (p = 0.0278). More infants in the variant MBL group had significant patent ductus arteriosus when compared to infants with wild-type MBL (27.8 vs. 9.5% respectively, p = 0.037). Conclusion: MBL gene polymorphism was associated with increased frequency of clinical sepsis particularly with early neonatal sepsis and also with higher Tollner sepsis scores and increased frequency of patent ductus arteriosus in infants. Overall mortality and incidence of culture proven sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia and necrotizing enterocolitis were not found to be related to MBL genotype. © 2010 S. Karger AG, Basel.

Oxygen-derived free radicals are important components of gastrointestinal injury in necrotizing enterocolitis (NEC). In the present investigation, we examined the protective actions of L-arginine, a nitric oxide synthase substrate, and L-carnitine against hypoxia-reoxygenation (H/R) induced NEC in young mice. Young mice were divided into four groups: group 1 mice were subjected to H/R only; group 2 H/R mice were supplemented with L-arginine in the drinking water (2 g/l) for 7 days; group 3 H/R mice were given L-carnitine solution in water (50 mg/kg p.o.) for 7 days, and group 4 mice served as controls.Hypoxia was induced by placing the mice in a 100% CO2 chamber for 5 min. After hypoxia, the mice were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions by light microscopy and measured the intestinal generation of thiobarbituric acid reactive substances (TBARS) and the activities of superoxide dismutase and catalase in the H/R-induced model of NEC. In both L-arginine and L-carnitine groups, the NEC-induced intestinal tissue damage was greatly attenuated, with necrosis limited partially to the mucosa. The tissue TBARS level was significantly higher in group 1 than in any of the other groups (p < 0.001). However, those treated with L-arginine and L-carnitine had TBARS levels similar to those in the control animals. An increased tissue concentration of nitrate, a stable metabolite of nitric oxide, was found in the L-arginine-supplemented group as compared with the control group (p < 0.05). Both superoxide dismutase and catalase activities in the intestine were similar in H/R groups when compared with the intestine of control animals. The present study suggests that oxygen-derived free radicals are involved in the pathogenesis of H/R-induced NEC. This study also shows that dietary supplementation with L-arginine and L-carnitine ameliorates the histological evidence of H/R-induced intestinal injury and significantly decreases lipid peroxidation in H/R-induced bowel injury. Based on these findings, the beneficial effects of L-arginine and L-carnitine in this model may be mediated via mechanisms preventing free radical damage.

Necrotizing entercolitis (NEC) is an important neonatal disease with a high mortality rate. Inflammatory mediators, such as mainly platelet-activating factor (PAF), leukotrienes (LT) and tumor necrosis factor play an important role in the genesis of NEC. Diets in Ω–3 (n–3) fatty acids appear to have an antiinflammatory effect, which is thought to be due to decreased active prostaglandins and leukotrienes production after incorporation of these fatty acids into cell membrane phospholipids. We investigated the protective effect of fish oil (source of n–3 fatty acids) on hypoxia-induced model of NEC. Young mice were divided into three groups; group 1 mice were fed standard chow (n–3 fatty acids-free), group 2 was fed a chow supplemented by 10% fish oil for 4 weeks. Group 3 mice served as control. We examined the intestinal lesions by light microscopy and measured intestinal tissue PAF and LB4 levels in hypoxia-induced model of NEC. Significantly increased intestinal PAF and LTB4 levels were found in group 1 mice when compared to group 2 and group 3 mice. The histopathology of the intestinal lesions in group 1 animals was characteristic of ischemic injury. In the n–3 fatty acids-supplemented animals these lesions were milder. The present study shows that endogenously released PAF and LTB4 play an important role in mediating hypoxia-induced intestinal necrosis. The present study also suggests that dietary supplementation with n–3 fatty acids suppress intestinal PAF and LTB4 generation in hypoxia-induced bowel necrosis. The intestinal protective effect of n–3 fatty acids in an experimental model of NEC may open new insight into the treatment and preventation of NEC in neonates.

Hypoxic-ischemic encephalopathy is still a very important cause of neonatal mortality and morbidity. Recently, platelet-activating factor (PAF) has been accused of being responsible for the neuronal damage in hypoxic-ischemic brain. We investigated tissue PAF concentrations in hypoxic-ischemic brain injury in immature rats. Endogenous PAF concentration in brain tissue showed a marked increase in hypoxic-ischemic pups (85.6 ± 15.5 pg/mg protein) when compared to that of control (9.05 ± 3.1 pg/mg protein). In addition, we examined the effects of flunarizine, a selective calcium channel blocker, and Ginkgo biloba extract (EGb 761) on endogenous PAF concentration in hypoxic-ischemic brain injury. Endogenous PAF concentrations in both flunarizine-pretreated (16.6 ± 4.8 pg/mg protein) and EGb 761-pretreated (33.5 ± 8.9 pg/mg protein) pups were significantly lower than the untreated group. These results indicate that PAF is an important mediator in immature rat model of cerebral hypoxic-ischemic injury. The suppressor effect of flunarizine and EGb 761 on PAF production may open new insight into the treatment of hypoxic-ischemic brain injury.

It is well known that necrotizing enterocolitis (NEC) is less frequent in newborns being fed human breast milk. Since recent studies indicated that platelet-activating factor (PAF) plays an important role in pathogenesis of NEC, this study was conducted to investigate the PAF levels in human milk. Colostrum and mature human milk (samples obtained in the third week) of three groups of mothers were investigated. The first group had given birth within less than 32 weeks, the second between 33–37 weeks and the third group after 38 weeks of gestation. The PAF levels in colostrum of all three groups were similar (0.95 ± 0.57, 1.05 ± 0.52 and 1.19 ± 0.64 ng/ml, respectively). Mature human milk in groups I and II had similar PAF levels (1.16 ± 0.54 and 1.21 ± 0.60 ng/ml, respectively), however, mature human milk in group III had a significantly higher PAF concentration (2.04 ± 0.59 ng/ml) than both groups’ levels. However, this phenomenon by itself does not explain the protective effect of human milk against NEC.

Background: A limited number of studies have reported various short-term cardiovascular changes in bronchopulmonary dysplasia (BPD) patients in the postsurfactant era. Little is known about the course of these changes in children with BPD. Objectives: It was the aim of this study to investigate cardiovascular consequences of BPD at preschool ages and to find out possible risk factors related to cardiovascular sequelae. Methods: Prematurely born children with (n = 21) and without BPD (n = 20) were evaluated with conventional and myocardial tissue Doppler echocardiography at the age of 2-4 years. Results: BPD patients had a decreased pulmonary artery acceleration time and higher left and right ventricular myocardial performance indexes, consistent with higher pulmonary pressures and impaired biventricular systolic and diastolic functions at preschool ages. Low birth weight, disease severity and postnatal cumulative steroid dose were related to these changes. Conclusion: Negative effects of BPD on global cardiac performances of both ventricles and pulmonary arterial pressure persist up to preschool ages.