Aytuğ Atıcı

Platelet-activating factor antagonist (ABT-491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury

Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. To date, no study has investigated the role of platelet-activating factor (PAF) antagonists on neuronal apoptosis in neonatal rat model of HIBI. In the present study, we evaluated the effect of a highly potent and selective PAF antagonist (ABT-491) on neuronal apoptosis in neonatal rat model of HIBI. Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2 h. They were treated with ABT-491 or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal-transferase mediated dUTP biotin nick-end-labeling (TUNEL) and caspase-3 staining methods. Administration of ABT-491 either before or after hypoxia resulted in significant reduction of the numbers of apoptotic cells in both hemispheres, when compared to saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups were significantly higher than that in the left hemispheres. These results suggested that ABT-491, a highly potent and selective PAF antagonist, administration either before or after hypoxia reduces apoptosis and we propose that ABT-491 may be a novel approach in the treatment of HIBI.

Bispectral Index Monitoring in Confirmation of Brain Death in Children

Although the guidelines for the diagnosis of brain death in children are well established, the diagnosis is still under debate, and further confirmatory tests are required. Performing these confirmatory tests presents some drawbacks, such as high costs, the need for specialized personnel and technology, transportation of patients out of the intensive care unit, and the use of contrast media. Bispectral index monitoring can provide real-time, objective, continuous monitoring of the consciousness level in critically ill children. The aim of this prospective study was to define the role of bispectral index monitoring in the confirmation and diagnosis of brain death. Eight children who had fulfilled the diagnostic criteria of brain death were included in the study. The age of patients ranged from 3 months to 15 years. All patients had electrocerebral silence on their electroencephalographic recordings. After the diagnosis of brain death, at least 2-hour monitoring was performed, and all patients expressed a score of 0, indicating brain death. According to our study, the decrease in bispectral index score to 0 in patients with suspected brain death can support and confirm brain death diagnosis in children and can enable scheduling of expensive tests, such as cerebral angiography, in the appropriate time. Nevertheless, further studies are needed to determine the role of the bispectral index in the diagnosis and confirmation of brain death in children. In this article, we review clinical utility, application time, and interpretation of bispectral index monitoring in confirmation of brain death diagnosis in children. (J Child Neurol 2006;21:799—801; DOI 10.2310/7010.2006.00131).

The effects of pentoxifylline on lung inflammation in a rat model of meconium aspiration syndrome

ABSTRACT To examine the effects of pentoxifylline (PTX) on regional pulmonary and systemic inflammation after meconium aspiration, we studied 26 anesthetized and ventilated adult rats for 3 hours. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally. After instillation of meconium, PTX (20 mg/kg, i.a.; n = 9) or saline (n = 8) was given to the subjects. Nine rats that were ventilated and not instilled with meconium served as sham group. Meconium instillation resulted in increased bronchoalveolar lavage (BAL) fluid tumor necrosis factor-α (TNF-α; P = 0.004 and P = 0.002, respectively), protein (P = 0.005 and P = 0.001, respectively) levels, and arterial oxygenation index (OI) in PTX and saline groups. PTX treatment prevented the increase of BAL fluid TNF-α, protein concentrations, and OI in the meconium-instilled lungs but had no statistically significant effect. These results indicate that meconium aspiration induces severe inflammation in the lung. PTX treatment affects the TNF-α production in the lungs and it may attenuate meconium-induced derangements.

A girl with spastic tetraparesis associated with biotinidase deficiency

Biotinidase deficiency is a disorder of biotin metabolism that manifests with cutaneous, ophthalmological and neurologyical symptoms in childhood. Spinal cord involvement has rarely been reported and all of the reported cases are spastic paraparesis. A 3 year-old girl with biotinidase deficiency was admitted to our clinic with hyperventilation, hair loss and spastic tetraparesis. To our knowledge, our case is the first reported tetraparesis associated with biotinidase deficiency. She was treated with oral biotin and benefited significantly from this therapy.

Mesenchymal stem cell treatment in hyperoxia-induced lung injury in newborn rats.

The aim of this study was to evaluate the effectiveness of tracheally delivered mesenchymal stem cells (MSC) on lung pathology in a hyperoxia‐induced lung injury (HILI) model in neonatal rats.

Comparison of selective head cooling versus whole-body cooling

This study compared selective head cooling (SHC) and whole‐body cooling (WBC) in newborns with hypoxic–ischemic encephalopathy (HIE).

Antioxidant Capacity of Breast Milk of Mothers who Delivered Prematurely is Higher Than That of Mothers who Delivered at Term

BACKGROUND The total antioxidant capacity of plasma of preterm infants has been suggested to be lower than that of term infants. The objective of this study was to compare the total antioxidant capacity of the breast milk of mothers who delivered prematurely with that of mothers who delivered at term. MATERIALS AND METHODS A total of 71 breast milk samples were collected, 41 from mothers who delivered preterm (27 to 37 weeks) and 30 from mothers who delivered at term (38 to 42 weeks). RESULTS The mean total antioxidant capacity of the breast milk of mothers who delivered prematurely was higher (2.19 ± 0.88 mmol/L) than that of mothers who delivered at term (1.7 ± 0.86 mmol/L) (p = 0.024). CONCLUSION Breastfeeding may protect preterm infants against oxidative stress and related disorders in the neonatal period.

The effect of tumor necrosis factor-α inhibitor soon after hypoxia-ischemia on heart in neonatal rats

AIMS Perinatal hypoxic-ischemic insult has acute and long term deleterious effects on many organs including heart. Although tumor necrosis factor alpha (TNF-α) has been reported to increase soon after hypoxia, the inhibition of this mediator has not been documented. The aim of this study was to investigate the effects of a TNF-α inhibitor (etanercept) on contractility and ultrastructure of rat heart muscles exposed to hypoxia-ischemia during neonatal period. MAIN METHODS Forty-five seven-day old rats divided into three groups were included in this study. The right carotid arteries of Saline and Etanercept groups of rats were ligated and kept in a hypoxia chamber containing 8% oxygen for 2h. Immediately after hypoxia, while Etanercept group was administered 10mg/kg etanercept, Saline group had only saline intraperitoneally. The carotid arteries of rats in Sham group were located without ligation and hypoxia. Mechanical activity of heart was recorded and tissue samples were examined by electron microscopy in the sixteenth week following the hypoxia-ischemia. KEY FINDINGS While atrial contractile force in Etanercept group was similar to Sham group, there was significant decrease in Saline group (p<0.001). However, there was only non-significant decrease in ventricular contractility of Saline group comparing to Sham group (p>0.05). After hypoxia-ischemia, ultrastructural degenerative changes and mitochondrial damage in atriums of Etanercept group were significantly less severe than Saline group. SIGNIFICANCE This study demonstrated that neonatal hypoxia-ischemia caused long term cardiac dysfunction and ultrastructural degenerative changes in the heart of rats. TNF-α inhibitor administration soon after hypoxia-ischemia may have heart protective effect.

The effects of fibroblast growth factor-2 and pluripotent astrocytic stem cells on cognitive function in a rat model of neonatal hypoxic-ischemic brain injury.

Abstract Objective: This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI). Methods: The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats’ cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months. Results: PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1–4 of MWM testing (p < 0.001). On day 2–4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3–4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms. Conclusions: Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance.

A case of thanatophoric dysplasia type 2: a novel mutation.

Thanatophoric dysplasia (TD) is a lethal form of skeletal dysplasia with short-limb dwarfism. Two types distinguished with their radiological characteristics have been defined clinically. The femur is curved in type 1, while it is straight in type 2. TD is known to be due to a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. We report a male patient who showed clinical findings congruent with TD type 2 and a new mutation in the FGFR3 gene, a finding which has not been reported previously.