Mansur Tatli

Selective Inhibition of Nitric Oxide in Hypoxic-Ischemic Brain Model in Newborn Rats: Is It an Explanation for the Protective Role of Erythropoietin?

Erythropoietin (Epo) exerts neuroprotection against neuronal death induced by ischemia and hypoxia in vitro and in vivo. Recent studies suggest that the neuroprotective effects of Epo may depend upon different mechanisms, including the inhibition of nitric oxide (NO). We recently demonstrated that Epo exerts neuroprotection in a model of neonatal hypoxic-ischemic brain damage. In the present study, we directly determined whether systemic administration of recombinant Epo modulates cerebral NO production in a neonatal rat model of hypoxic-ischemic brain injury. Seven-day-old Wistar rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure. Brain nitrite levels were evaluated in both hemispheres (carotid ligated or nonligated) by Griess reagent 72 h after the hypoxic-ischemic insult. Our results show that hypoxic-ischemic insult results a significant increase in NO production as compared with NO levels in hypoxic hemispheres and control animals. A single dose of Epo treatment (1,000 U/kg i.p.) significantly decreased NO overproduction in the hypoxic-ischemic hemisphere, whereas no significant change appeared in hypoxia alone or in controls. These data suggest that the selective inhibitory effect of Epo on NO overproduction could have a neuroprotective effect in neonatal hypoxic-ischemic brain injury.

Altered anti-oxidant status and increased lipid peroxidation in marasmic children.

Abstract Background: Protein energy malnutrition (PEM) is a common pediatric health problem in developing countries. Although the clinical features of PEM are well known, its pathophysiology is still unclear. Free radicals have been implicated in pathogenesis of PEM. In the present study, oxidant/anti‐oxidant status in marasmus was investigated.

Spontaneous intestinal perforation after oral ibuprofen treatment of patent ductus arteriosus in two very-low-birthweight infants.

Aim: To discuss intestinal side effects of ibuprofen in the treatment of patent ductus arteriosus, after having observed two cases of spontaneous intestinal perforation following ibuprofen treatment. Methods: Clinical and laboratory records of two preterm infants, who developed intestinal perforation after ibuprofen administration, were evaluated. Results: Gestational ages of infants were 29 wk (male) and 30 wk (female). Both infants developed intestinal perforations without signs of necrotizing enterocolitis. The perforations cured with Penrose drainage alone.

Transient tachypnea of the newborn: Predictive factor for prolonged tachypnea

Background: Because there is a lack of well‐established criteria, the aim of the present paper was to determine risk factors to predict the duration of tachypnea in transient tachypnea of the newborn (TTN).

Erythropoietin Protects against Necrotizing Enterocolitis of Newborn Rats by the Inhibiting Nitric Oxide Formation

Background: Necrotizing enterocolitis (NEC) is an important neonatal disease with a high mortality rate; erythropoietin (Epo) is a hematopoietic growth factor. Functional Epo receptors are in the fetal and postnatal small bowel and their ligands are available for binding. Excessive nitric oxide (NO) production by an isoform of NO synthase inducible by inflammatory stimuli leads to changes in vascular permeability and tissue injury. The aim of this study was to investigate NO formation in an experimental model of NEC and the possible role of NO in the protection Epo provides against NEC. Methods: Twenty-four Wistar albino rat pups were divided into three groups: group 1 = control; group 2 = hypoxia-reoxygenation and saline; group 3 = hypoxia-reoxygenation and recombinant human EPO (rhEpo) pretreatment. rhEpo was given 750 U/kg/week by intraperitoneal injection 3 times a week for 2 weeks. On the 15th day, hypoxia was induced by placing the pups in a 100% CO2 chamber for 5 min. After the hypoxia period the pups were reoxygenated for 10 min with 100% O2 and returned to their mothers. All pups were killed 4 h after the hypoxia-reoxygenation period was over. The abdomen was opened and representative samples of injured areas were taken for histopathologic examination. Then nitrite levels were determined in the intestine by Griess Reagent. Results: On histopathological examination, injury scores in group-2 animals were found to be significantly higher than in group-3 animals (p = 0.001). Significantly increased intestinal nitrite levels were found in group-2 rats compared to the rats of groups 1 and 3 (p = 0.001 and p = 0.001, respectively). There was a positive correlation between the histological findings and the intestinal nitrite levels in group-2 and -3 animals (r = 0.94, p = 0.001; r = 0.99, p = 0.001, respectively). Conclusion: The present study demonstrates that the Epo-pretreated group had decreased levels of NO and limited mucosal necrosis in intestinal tissue samples. We believe that these results deserve further experimental studies in order to elucidate the possible effector mechanisms involved in the inhibitory relationship between Epo, NO and NEC.

Hyperbilirubinemic Serum Is Cytotoxic and Induces Apoptosis in Murine Astrocytes

Background: High levels of unconjugated bilirubin can be neurotoxic and gliotoxic. However, the effect of serum from patients with neonatal indirect hyperbilirubinemia on astrocyte viability has never been investigated. Objectives: In the present study, we searched for the possible toxic effect of hyperbilirubinemic serum on murine astrocytes. Methods: Heat-inactivated patient serum was added to astrocyte cultures at different concentrations varying from 1 to 20%, and cultures were incubated for 24, 48, and 72 h. Sera from healthy infants without hyperbilirubinemia were used as controls. Cytotoxicity was evaluated according to the release of lactate dehydrogenase in the culture medium. Apoptotic cell death was determined by anti-single-strand DNA immunostaining. Results: The results of the present study show that hyperbilirubinemic serum induces cytotoxicity and apoptotic astrocyte death in a concentration- and time-dependent manner. Conclusions: We conclude that serum from patients with neonatal indirect hyperbilirubinemia is cytotoxic to murine astrocytes.

Feasibility of neonatal hearing screening program with two-stage transient otoacoustic emissions in Turkey

Background: The objective of this study was to investigate the incidence of hearing loss in neonates and evaluate the feasibility of a two‐stage Transient Evoked Otoacoustic Emission (TEOAE) screening test. Maternal concerns about hearing screening were also studied.

Erythroid Apoptosis in Idiopathic Neonatal Jaundice

OBJECTIVES. The objectives of this study were to evaluate the contribution of erythroid apoptosis to neonatal idiopathic pathologic jaundice and to determine whether a measurement of the erythroid apoptosis value at birth could predict the development of hyperbilirubinemia during the first 15 days of life. PATIENTS AND METHODS. Three groups were defined: group 1 (n = 101), healthy newborns whose erythroid apoptosis value and serum total bilirubin levels were detected from birth to day 15; group 2 (n = 24), newborns who were hospitalized for jaundice (serum total bilirubin level: >12.9 mg/dL) without any identifiable pathologic cause; and group 3 (control group, n = 24), healthy newborns whose serum total bilirubin levels were ≤12.9 mg/dL. Erythroid apoptosis value was assessed by flow cytometry using an annexin-V fluorescein isothiocyanate kit. RESULTS. In group 1, there was no correlation between the erythroid apoptosis value and serum total bilirubin levels obtained at birth and at the fourth and 15th days of life; the erythrocyte apoptosis value obtained at birth was not significantly different between the neonates whose serum total bilirubin levels were >12.9 and ≤12.9 mg/dL and who had prolonged and nonprolonged jaundice during follow-up. The erythroid apoptosis value differed significantly between the newborns in groups 2 and 3. There was no significant correlation between the erythroid apoptosis value and serum total bilirubin levels of the infants in groups 2 and 3. CONCLUSIONS. The erythroid apoptosis value obtained at birth could not predict the development of hyperbilirubinemia in neonates, but it was increased significantly in jaundiced neonates whose serum total bilirubin levels were >12.9 mg/dL. In these infants, increase in the erythroid apoptosis value may be a result of the toxic effect of bilirubin or of a protective mechanism of neonates to increase heme turnover and bilirubin production to diminish oxidative stress.