Ali Haydar Turhan

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.

Bilateral adrenal cystic neuroblastoma with massive hepatomegaly and intracystic hemorrhage

To The Editor: Cystic neuroblastoma (CNB) is a rare form of this tumor which is characterized by a large cystic lesion and microscopic cysts, and is frequently located in the adrenal gland. It has a little tendency to metastasis and it has an excellent prognosis if early diagnosis can be made [1–10]. Furthermore, bilateral adrenal CNB is an extremely unusual presentation of NB which may represent a second primary tumor or a contralateral metastasis [4]. Most of the patients with CNB are under 1 year of age. Moreover, massive intratumoral hemorrhage, hepatic metastases, and advanced clinical stage are also rare clinical findings. The differential diagnosis of a cystic suprarenal mass is difficult since it occurs not only in CNB, but also in adrenal hemorrhage, enteric cyst, extralobar sequestration, dilatation of upper-pole renal calyces, congenital adrenal cyst, cystic Wilms tumor, and adrenal abscess [2–4]. A 19-day-old girl, being born in another hospital, was admitted to our hospital with the symptoms of paleness, respiratory distress, and abdominal distention. Physical examination revealed tachycardia, tachypnea, hepatomegaly, and a large left-sided abdominal mass. Laboratory findings were as follows: hemoglobin 5.6 g/dl, serum lactate dehydrogenase 1,367 U/L, neuron specific enolase 56 ng/ml, ferritin 220 ng/ml, and urine vanillylmandelic acid 29.5 mg/day. Bone marrow infiltration with tumor cells (8%) was also found. Thorax CT revealed geometric shaped subpleural densities in the lungs consistent with atelectasis. Furthermore, CT scan of the abdomen showed bilateral adrenal cystic mass lesions with intracystic echogenities and fluid levels, suggesting intracystic hemorrhage. Besides hepatosplenomegaly, multiple hypodense lesions conforming to metastases in the liver were also observed (Fig. 1). Radionuclide bone scan was negative. Clinical diagnosis was congenital bilateral CNBwith liver metastases. However, lung metastases were also suspected. Since primary surgery could not be performed, chemotherapy was initiated. On the 8th day of chemotherapy, the patient died of extensive hepatic involvement, which caused respiratory and inferior vena cava compromise. Histopathologic examination revealed neuroblastoma cells at the wall of the almost entirely hemorrhagic cystic masses with favorable histology according to the Shimada classification, and lung, liver, and spleen involvement (Fig. 2). DNAcontent, N-myc expression, and allelic loss of chromosome 1p could not be obtained. Differentiation between adrenal hemorrhage and adrenal CNB is especially important because the treatment of hemorrhage is generally conservative. Although intratumoral hemorrhage is common in CNB, massive symptomatic hemorrhage is a rare finding [1,4,6]. To our knowledge, there have been only three reported cases with bilateral adrenalCNBwith intracystic hemorrhage [4,6,8]. In the newborn, reported by Lee et al. [4] the presence of the liver metastases made differential diagnosis easier as in our case. Since the other two reported cases with bilateral CNB which were diagnosed after the first month of life did not have liver involvement, the differential diagnosis of adrenal hemorrhagewas difficult [6,8]. MR imaging seems to be a good alternative radiological method in this differential diagnosis [6,9]. Most patientswithCNBare diagnosed in the early stage of disease with an excellent long-term prognosis, except patients with stage IV disease, hydrops, or massive hepatomegaly [2,3,10]. Only 9.7% of cases with CNB have metastatic disease at diagnosis [7]. When present, as in our case, the fetal liver is themost common site [5]. Two of three reported children with bilateral CNB had stage IVS, but one patient had stage IV disease. In children with CNB, less aggressive management may be warranted in the absence of stage IV disease. Some authors recommend that prenatally suspected non-metastatic CNB should undergo surgical intervention, unless tumor size decreases within about 1 month after birth [2,9]. While chemotherapy is necessary for advanced disease, as in our case, radiotherapy may be used in patients with unresectable or incompletely resected tumors [4]. One of two reported cases with bilateral CNB of stage IVS, to whom only surgical resection was performed, was lost to follow up,

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.

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.

Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome

ABSTRACT Background: Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). Purpose of the Study: The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. Materials and Methods: In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. Results: Intrapulmonary instillation of meconium resulted in the increase of TNF-α (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1β, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). Conclusion: rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements.

Comparison of selective head cooling therapy and whole body cooling therapy in newborns with hypoxic ischemic encephalopathy: short term results.

AIM In this study, it was aimed to investigate which method was superior by applying selective head cooling or whole body cooling therapy in newborns diagnosed with moderate or severe hypoxic ischemic encephalopathy. MATERIALS AND METHOD Newborns above the 35th gestational age diagnosed with moderate or severe hypoxic ischemic encephalopathy were included in the study and selective head cooling or whole body cooling therapy was performed randomly. The newborns who were treated by both methods were compared in terms of adverse effects in the early stage and in terms of short-term results. Ethics committee approval was obtained for the study (06.01.2010/35). RESULTS Fifty three babies diagnosed with hypoxic ischemic encephalopathy were studied. Selective head cooling was applied to 17 babies and whole body cooling was applied to 12 babies. There was no significant difference in terms of adverse effects related to cooling therapy between the two groups. When the short-term results were examined, it was found that the hospitalization time was 34 (7-65) days in the selective head cooling group and 18 (7-57) days in the whole body cooling group and there was no significant difference between the two groups (p=0.097). Four patients in the selective head cooling group and two patients in the whole body cooling group were discharged with tracheostomy because of the need for prolonged mechanical ventilation and there was no difference between the groups in terms of discharge with tracheostomy (p=0.528). Five patients in the selective head cooling group and three patients in the whole body cooling group were discharged with a gastrostomy tube because they could not be fed orally and there was no difference between the groups in terms of discharge with a gastrostomy tube (p=0.586). One patient who was applied selective head cooling and one patient who was applied whole body cooling died during hospitalization and there was no difference between the groups in terms of mortality (p=0.665). CONCLUSIONS There is no difference between the methods of selective head cooling and whole body cooling in terms of adverse effects and short-term results.

Effects of hypothermia on lung inflammation in a rat model of meconium aspiration syndrome

PURPOSE To evaluate the effects of hypothermia treatment on meconium-induced inflammation. METHODS Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. RESULTS The BAL fluid TNF-α, IL-1β, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). CONCLUSION Meconium-induced inflammatory cytokine production is affected by the body temperature control.

Accessory Nostril: A Rare Congenital Nasal Anomaly.

Accessory nostril is a very rare congenital anomaly with an unknown etiology also known as supernumerary nostril. A few accessory nostrils have been reported up to the present time, and extremely rare cases located on columella. A newborn infant with respiratory distress was referred to our hospital. The authors observed that accessory nasal nostril is not related to normal nasal cavity on the median line of columella. In this article, the authors reported accessory nostril case in newborn and review the literature.

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

ABS TRACT Ob jec ti ve: Ne o na tal hypo xic-isc he mic (HI) in sult has acu te and long term de le te ri o us ef fects on many tis su es inc lu ding the pe rip he ral ner ves. To da te, no study has in ves ti ga ted the ro le of pla te let-ac ti va ting fac tor (PAF) an ta go nists on pe rip he ral ner ve da ma ge in a ne o na tal rat mo del of HI. In this study, we exa mi ned the ef fects of PAF an ta go nist (ABT-491) on pe rip he ral ner ve da ma ge in rats in the 16th we ek that we re ex po sed to HI on 7th day af ter birth. Ma te ri al and Met hods: Se ven-day-old Wis tar rat pups we re sub jec ted to right com mon ca ro tid ar tery li ga ti on and hypo xi a (92% nit ro gen and 8% oxy gen) for one ho ur. They we re tre a ted eit her with ABT-491 (n=19) or sa li ne (n=20) im me di a tely af ter hypo xi a. In sham gro up (n=20), ne it her li ga ti on nor hypo xi a was per for med. The com po und mo tor ac ti on po ten ti al (CMAP) re cor dings of all ani mals we re ma de in the six te enth we ek fol lo wing the HI. For CMAP re cor dings, bi po lar sti mu la ting elec tro des we re pla ced on the sci a tic ner ve. Upon sti mu la ti on, two sur fa ce elec tro des, pla ced over the gas troc ne mi us musc le, re cor ded com po und musc le ac ti on po ten ti als. Re sults: The amp li tu de of CMAP re cor ded from the rats tre a ted with sa li ne af ter hypo xi a was smaller com pa red to the sham gro up. However, the CMAP re cor ded from the gro up tre a ted with ABT-491 af ter HI was not sig ni fi cantly dif fe rent from the sham gro up. Conc lu si on: This study imp li es that HI has axo nal da ma ge on pe rip he ral ner ve but a PAF an ta go nist ABT-491 has a pre ven ti ve ef fect on the axo nal dysfunc ti on af ter HI.