Mustafa Kul

Publications of Mustafa Kul

• Role of Cyclooxygenase 2 and Endothelial Nitric Oxide Synthetase in Preclinical Atherosclerosis.

  Authors: Abdulbaki Karaoglu, Turan Tunc, Gokhan Aydemir, Onder Onguru, Bulent Uysal, Mustafa Kul, Secil Aydinoz, Emin Oztas, Umit Sarici

  Fetal and pediatric pathology. 03/2012;

  Cyclooxygenase-2 and endothelial nitric oxide (NO) synthase enzymes may have a role in developing preclinical atherosclerosis. Designed groups were as follows: smoke exposed rats before and duringCyclooxygenase-2 and endothelial nitric oxide (NO) synthase enzymes may have a role in developing preclinical atherosclerosis. Designed groups were as follows: smoke exposed rats before and during pregnancy, only before pregnancy, and controls. Cross-sectional samples of abdominal aorta were examined immunohistochemically. Cyclooxygenase-2 and eNOS expression was evaluated semi-quantitatively through staining extent (focal, diffuse) and staining intensity. Diffuse COX-2 expression was detected in study groups. Endothelial NO synthase expression was diffuse in study groups. COX-2 and eNOS may contribute to the formation of preatherosclerotic lesions in offspring of rats exposed to cigarette smoke through inflammatory response.

• Passive smoke exposure of female rats caused aortic atherosclerotic precursor lesions in their offspring.

  Authors: Turan Tunc, Umit Sarici, Secil Aydinoz, Onder Onguru, Abdulbaki Karaoglu, Bulent Uysal, Mustafa Kul, Yusuf Sinan Sirin, Emin Oztas, Halil Yaman

  Fetal and pediatric pathology. 03/2012; 31(3):120-7.

  The aim of this study was to evaluate the presence and degree of preclinical atherosclerosis in pups of pregnant rats exposed to cigarette smoke. Abdominal aorta examined for atherosclerotic lesionsThe aim of this study was to evaluate the presence and degree of preclinical atherosclerosis in pups of pregnant rats exposed to cigarette smoke. Abdominal aorta examined for atherosclerotic lesions and intimal medial thickness of the abdominal aorta was measured by image analysis. The study groups showed endothelial cellular losses, marked intimal injuries, elastic fiber damages, mononuclear cellular infiltration, and irregularities in internal elastic membrane, with pronounced damages as integrity losses and local fragmentations. The results provide evidence for development of an atherosclerotic process in the neonatal period, even in prenatal stage, long before the formation of smoke-related cardiovascular diseases.

• The relation between delivery type and tau protein levels in cord blood.

  Authors: Turan Tunc, Abdulbaki Karaoglu, Tuncer Cayci, Erkan Demirkaya, Mustafa Kul, Halil Yaman, Sinan Karadeniz, Tayfun Gungor, Faruk Alpay

  Pediatrics international : official journal of the Japan Pediatric Society. 12/2010; 52(6):872-5.

  The perinatal morbidity risk is higher in operative deliveries than normal vaginal deliveries. 'Tau protein' is a cytoskeletal component that is predominantly expressed in axons of neurons. The aimThe perinatal morbidity risk is higher in operative deliveries than normal vaginal deliveries. 'Tau protein' is a cytoskeletal component that is predominantly expressed in axons of neurons. The aim of this study was to investigate whether delivery type, particularly the forceps application, had any effect on cord blood tau levels. Ninety babies born in the Division of Maternal-Fetal Medicine of Ankara Etlik Maternity and Women's Health Teaching Hospital, Ankara, Turkey were involved in the study. The babies were divided into three groups according to delivery type: Group 1: normal vaginal delivery (NVD); Group 2: caesarean section; Group 3: forceps application. Cord blood samples were drawn from umbilical veins of the babies soon after the birth. The cord blood tau protein levels in the caesarean section group (79 pg/mL [45-223]) were found to be significantly lower than those of NVD (135 pg/mL [44-627]) and forceps (175 pg/mL [17-418]) groups (P = 0.001 and P < 0.001, respectively). We have shown that forceps applications uncomplicated with perinatal asphyxia did not affect the cord blood tau protein level significantly. Tau levels in caesarean section group were significantly lower than the other two groups. Caesarean section in this manner might be considered especially in conditions of risk of perinatal asphyxia to avoid hypoxia.

• Evaluation of effects of s-methyl isothiourea and melatonin on intestinal ischemia/reperfusion injury in rats.

  Authors: Turan Tunc, Hilmi Demirin, Abdulbaki Karaoglu, Vural Kesik, Abdulkerim Temiz, Mehmet Ozler, Serdar Sadir, Cuneyt Atabek, Mustafa Kul, Emin Oztas, Ahmet Korkmaz

  Fetal and pediatric pathology. 01/2010; 29(4):212-23.

  The present study was designed to evaluate whether the administration of s-methylisothiourea and melatonin has protective potential in intestinal ischemia/reperfusion injury. Forty maleThe present study was designed to evaluate whether the administration of s-methylisothiourea and melatonin has protective potential in intestinal ischemia/reperfusion injury. Forty male Sprague-Dawley rats were divided into five groups. Ileal specimens were obtained to determine the levels of malondialdehyde, protein carbonyl content, levels of antioxidant enzymes and evaluation of histologic changes. Combination of s-methylisothiourea and melatonin, led to a statistically significant increase in activities of antioxidant enzymes with a decrease in malondialdehyde and protein carbonyl content and intestinal mucosal injury scores. It was shown; combination of SMT and melatonin may exert more promised results.

• Enteral Glutamine and/or Arginine Supplementation Have Favorable Effects on Oxidative Stress Parameters in Neonatal Rat Intestine.

  Authors: Mustafa Kul, Sabahattin Vurucu, Erkan Demirkaya, Turan Tunc, Seçil Aydinoz, Cihan Meral, Vural Kesik, Faruk Alpay

  Journal of pediatric gastroenterology and nutrition. 06/2009;

  OBJECTIVE:: To investigate and compare the effects of enteral glutamine and arginine supply on lipid peroxidation and antioxidant enzyme levels in the small intestine of healthy breast-fed rats.OBJECTIVE:: To investigate and compare the effects of enteral glutamine and arginine supply on lipid peroxidation and antioxidant enzyme levels in the small intestine of healthy breast-fed rats. MATERIALS AND METHODS:: The study comprised 40 newborn Sprague-Dawley rats born to 5 mother rats. Newborn rats were randomly divided into 4 groups. Starting from day 1 until day 21, group I received only breast milk; group II received breast milk and 200 mg/kg/day oral glutamine; group III received breast milk and 200 mg/kg/day oral arginine; and group IV received breast milk, 200 mg/kg/day glutamine, and 200 mg/kg/day arginine. Malondialdehyde levels and glutathione peroxidase (GPx) and superoxide dismutase activities were measured. RESULTS:: The lowest malondialdehyde levels were found in group II (P = 0.0001). Superoxide dismutase activity was found to be significantly higher in group II than group I (P < 0.001). Of the 4 groups, GPx activity was highest in group IV. GPx activity in group II was significantly higher than in group I (P = 0.001) or group III (P = 0.001). GPx activity was higher in group IV than in group I (P = 0.001) or group III (P = 0.001). CONCLUSIONS:: Enteral glutamine alone or in the presence of arginine has favorable effects on oxidative stress not only in experimental models of hypoxia-reoxygenation, but also in healthy newborn rats. This suggests that in premature neonates with insufficient oxidative resistance, glutamine and arginine supplementation may help prevent necrotizing enterocolitis.

• Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress.

  Authors: Mustafa Gulgun, Onur Erdem, Emin Oztas, Vural Kesik, Necati Balamtekin, Sebahattin Vurucu, Mustafa Kul, Erol Kismet, Vedat Koseoglu

  Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie. 04/2009;

  Mucositis is an important dose-limiting side effect of methotrexate for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proanthocyanidin had aMucositis is an important dose-limiting side effect of methotrexate for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proanthocyanidin had a protective effect on methotrexate-induced small intestine damage. Twenty-eight albino rats were randomized into four groups. To the first group, methotrexate was applied as a single dose (20mg/kg) intraperitoneally. To the second group, proanthocyanidin (100mg/kg) was given orally every day by gavage in addition to methotrexate application until the rats were killed. To the third group, only proanthocyanidin was administered. The fourth group was the control. All animals were sacrificed 4 days after the intraperitoneal injection of methotrexate for histopathological examination and the assay for tissue malondialdehyde, superoxide dismutase and glutathione peroxidase levels. Methotrexate caused jejunal injury and increased malondialdehyde levels. Administration of proanthocyanidin decreased the jejunal damage and malondialdehyde level, which were caused by methotrexate treatment and increased superoxide dismutase and glutathione peroxidase levels. These results suggest that proanthocyanidin may protect the small intestine of rats from methotrexate-induced damage. The effects of proanthocyanidin could result from its antioxidant properties.

• Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model.

  Authors: Ahmet Guven, Gokhan Gundogdu, Bulent Uysal, Hakan Cermik, Mustafa Kul, Suzi Demirbag, Haluk Ozturk, Sukru Oter

  Journal of pediatric surgery. 04/2009; 44(3):534-40.

  INTRODUCTION: Hyperbaric oxygen (HBO) therapy is known to increase oxygen concentration in tissues leading to induction of an adaptive increase in antioxidants, stimulation of angiogenesis,INTRODUCTION: Hyperbaric oxygen (HBO) therapy is known to increase oxygen concentration in tissues leading to induction of an adaptive increase in antioxidants, stimulation of angiogenesis, improvement of white blood cell action, and regulation of inflammatory process. Therefore, we tested the potential beneficial effect of HBO in neonatal rat model of necrotizing enterocolitis (NEC). MATERIALS AND METHODS: Thirty newborn Sprague-Dawley rats, provided by the Experimental Research Council, Gulhane Military Medical Academy, Ankara,Turkey, were randomly divided into 3 groups as follows: NEC, NEC + HBO, and control. Necrotizing enterocolitis was induced by enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C and oxygen. The NEC + HBO group received HBO at 2.8 atmosphere absolute (ATA) for 90 minutes daily for 3 days. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood samples were also obtained from the pups. RESULTS: The mortality rate was highest in the NEC group (3 pups in the NEC group vs 1 pup in the NEC + HBO group). Malondialdehyde and protein carbonyl content were significantly increased, whereas superoxide dismutase and glutathione peroxidase were significantly decreased in the NEC group. All these changes were similar to control levels in the NEC group by HBO treatment. Nitrate plus nitrite (NO(x)) levels and serum tumor necrosis factor alpha were increased in the NEC group and histopathologic injury score and apoptosis index in the NEC group were significantly higher than in the NEC + HBO group. CONCLUSION: Hyperbaric oxygen significantly reduced the severity of NEC in our study.

• Protective effect of sulfhydryl-containing antioxidants against ischemia/reperfusion injury of prepubertal rat intestine.

  Authors: Turan Tunc, Sükrü Oter, Ahmet Güven, Turgut Topal, Mustafa Kul, Ahmet Korkmaz, Onder Ongürü, Umit Sarici

  Journal of gastroenterology and hepatology. 01/2009;

  Abstract Background and Aim: Reactive oxygen species generated during reperfusion of the tissue are known to play an important role in the basic pathophysiology of ischemia/reperfusion (I/R) injury.Abstract Background and Aim: Reactive oxygen species generated during reperfusion of the tissue are known to play an important role in the basic pathophysiology of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate and compare the protective effects of three sulfide-based antioxidants, N-acetylcysteine (NAC), erdosteine (ERD), and alpha-lipoic acid (LA), on I/R injury of the small intestine tissue. Methods: Forty male Sprague-Dawley rats weighing between 100-150 g were divided into five groups (n = 8 for each): control (sham operated), I/R, I/R + NAC, I/R + ERD, and I/R + LA. Intestinal ischemia was provided by occluding the superior mesenteric artery via a special microvascular clamp; ischemia for 30 min and reperfusion for 3 days were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehyde (MDA), protein carbonyl contents (PCO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and histological changes. Results: The rats subjected to intestinal I/R exhibited an increase in tissue MDA and PCO; the levels could hardly be ameliorated in the treatment groups. SOD and GPx activities were significantly decreased in the I/R group, whereas their reduction was less expressed in the treatment groups. Additionally, the histopathological injury scores of the disulfide-treated groups were lower than those of the I/R group. Conclusion: All of the sulfhydryl-containing antioxidants used in this study exhibited a significant role in attenuating intestinal I/R injury; however, the outcome of the LA-treated group was significantly marked than that of the others.

• Chitotriosidase activity in human milk from mothers of premature and full-term infants during the first month of lactation.

  Authors: Turan Tunc, Mustafa Kul, Halil Yaman, Erkan Demirkaya, Mehmet Saldir, Ismail Kurt, S Umit Sarici, Faruk Alpay

  Clinical biochemistry. 07/2008; 41(9):693-6.

  OBJECTIVE: The objectives of the present study were to measure the activity of chitotriosidase (ChT) in human milk, to record changes in enzyme activity over time and to determine whether there areOBJECTIVE: The objectives of the present study were to measure the activity of chitotriosidase (ChT) in human milk, to record changes in enzyme activity over time and to determine whether there are differences in activity between the milk of mothers of full-term (FT) and premature (PT) infants. PATIENTS AND METHODS: Three samples were collected from each of 28 mothers (26.9+/-4.3 years of age; mean+/-SD) of FT infants (gestational age, 39.1+/-0.9 weeks; birth weight, 3384.8+/-369.8 g.; median, 3485 g) and 28 mothers (26.6+/-3.6 years of age) of healthy PT infants (gestational age, 30.5+/-3.1 weeks; birth weight, 1400+/-492.9 g.; median, 1285 g). Samples were collected at 3, 7 and 28th days after delivery. ChT activity was estimated using the fluorimetric method. ChT activities were calculated and expressed as nanomoles per milliliter per hour. RESULTS: ChT activity was higher in the PT group than in the FT group at day 3 [170.2 (14.0-294.8) vs. 81.7 (6.9-306.3) nmol/mL/h], day 7 [31.6 (0.0-166.7) vs. 17.2 (0.0-214.1) nmol/mL/h] and day 28 [5.5 (0.0-64.9) vs. 3.4 (0.0-51.6) nmol/mL/h]. CONCLUSION: The higher ChT activity in milk of mothers of PT infants than those of FT infants suggests the presence of activated macrophages as its main source. ChT is well known to play a role in defense against fungi and have the ability to degrade both colloidal chitin and chitin in the cell wall of Candida albicans. Thus, our findings may indicate that infants have a natural advantage for protection from fungus infections when they are fed by their mothers' milk.

• Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy.

  Authors: Sebahattin Vurucu, Erkan Demirkaya, Mustafa Kul, Bulent Unay, Davut Gul, Ridvan Akin, Erdal Gokçay

  Progress in neuro-psychopharmacology & biological psychiatry. 05/2008; 32(3):844-8.

  Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 areHomocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.

• Acinetobacter septicus sp. nov. association with a nosocomial outbreak of bacteremia in a neonatal intensive care unit.

  Authors: Abdullah Kilic, Haijing Li, Alexander Mellmann, Ahmet C Basustaoglu, Mustafa Kul, Zeynep Senses, Hakan Aydogan, Charles W Stratton, Dag Harmsen, Yi-Wei Tang

  Journal of clinical microbiology. 04/2008; 46(3):902-8.

  Acinetobacter species other than Acinetobacter baumannii have rarely been reported to be associated with nosocomial outbreaks of bloodstream infections. Within a period of 1 week, sevenAcinetobacter species other than Acinetobacter baumannii have rarely been reported to be associated with nosocomial outbreaks of bloodstream infections. Within a period of 1 week, seven Acinetobacter-like isolates were recovered from peripheral blood and catheter specimens of five patients at a neonatal intensive care unit (NICU) in a tertiary hospital in Turkey. All five patients had placement of central venous catheters and had received total parenteral nutrition before the onset of bacteremia. Two of the five patients died. Medical devices, tap water, aerators, water samples, various surfaces, intravenous fluids, and the hands of health care workers in the NICU were sampled and were culture negative for the bacterium. All seven of the isolates had identical biochemical reactions, antimicrobial susceptibility results, and pulsed-field gel electrophoresis patterns, indicating a clonal nosocomial outbreak. A panel of standard biochemical reaction profiles and three phenotypic commercial identification systems failed to identify these isolates. Phenotypically, the isolate differed from Acinetobacter ursingii by its hemolysis on sheep blood agar and its negative citrate utilization. Sequences of the full 16S rRNA gene, which contained at least three different gene copies with polymorphic sequences between nucleotide positions 70 and 206, were determined from the first recovered isolate. The complete 1,529- to 1,531-bp 16S rRNA gene sequences and partial 801-bp rpoB gene sequences had similarities of 99.5% and 97.2%, respectively, to an A. ursingii isolate. The DNA-DNA similarities of the strain against the type strain of A. ursingii were 64.7 and 68.7%, which were lower than the recommended threshold value of 70% for the definition of bacterial species. These data indicate that a novel Acinetobacter organism caused the nosocomial outbreak of bacteremia in the NICU unit. We propose the designation of Acinetobacter septicus sp. nov. for these isolates, with isolate AK001 as the type strain.

• alpha-Lipoic acid and ebselen prevent ischemia/reperfusion injury in the rat intestine.

  Authors: Ahmet Guven, Turan Tunc, Turgut Topal, Mustafa Kul, Ahmet Korkmaz, Gokhan Gundogdu, Onder Onguru, Haluk Ozturk

  Surgery today. 01/2008; 38(11):1029-35.

  PURPOSE: Reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study toPURPOSE: Reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study to evaluate the protective effect of alpha-lipoic acid (alpha-LA) and ebselen against intestinal I/R injury. METHODS: Forty Sprague-Dawley rats were divided into five groups: a sham-operated group; an I/R group, subjected to intestinal ischemia for 45 min and reperfusion for 3 days; an I/R+alpha-LA group; an I/R+ebselen group; and an I/R+alpha-LA+ebselen group. We collected ileal specimens, to measure the tissue levels of malondialdehyde (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and to evaluate the histologic changes. RESULTS: There was a significant decrease in SOD and GPx levels, with an increase in MDA and PCC levels and intestinal mucosal injury in the intestinal I/R group (P < 0.05). Superoxide dismutase and GPx levels were significantly higher, MDA and PCC levels were significantly lower, and intestinal injury was significantly less severe in the I/R+alpha-LA+ebselen group than in the I/R group (P < 0.05). Although shortened villi and epithelial lifting were seen in the I/R group, only slight mucosal injury was seen in the treatment groups. CONCLUSION: alpha-Lipoic acid and ebselen played an important role in attenuating I/R injury of the intestine by scavenging ROS and RNS.

• Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid.

  Authors: Nadir Korkmazer, Sebahattin Vurucu, Erkan Demirkaya, Bulent Unay, Mustafa Kul, Ridvan Akin, Erdal Gokcay

  Brain & development. 10/2006; 28(8):515-20.

  Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbancesValproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including anorexia and nausea, and hepatoxicity. As to its dose-dependent side effects are the weight loss, tremor, skin eruption and the alopecia. In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver biotinidase enzyme activities, serum AST, ALT, albumin, and valproic acid levels were measured. Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver biotinidase enzyme activities and the serum valproic acid levels, and the negative correlation between the liver tissues biotinidase activities and the serum valproic acid levels were noted, respectively. As a conclusion, the partial alopecia which is an initial symptom of reduced biotinidase activity may also be created depending on the reduction of biotinidase activity during valproic acid therapy. The alopecia which may further be observed in the patients receiving valproic acid therapy may be prevented by means of administration of biotin in a dose of 10 mg/day.

• Neonatal jaundice coinciding with or resulting from urinary tract infections?

  Authors: S U Sarici, Mustafa Kul, Faruk Alpay

  Pediatrics. 12/2003; 112(5):1212-3; author reply 1212-3.

• Perinatal risk factors affecting the maternal and fetal asymmetric dimethylarginine levels.

  Authors: Mustafa Kul, Erkan Demirkaya, Osman Metin Ipçioğlu, Rahmi Sinan Karadeniz, Turan Tunç, Sebahattin Vurucu, Fahri Gürkan Yeşil, Hasan Oztin, Erdinç Cakir

  The Turkish journal of pediatrics. 51(2):141-5.

  The aim of this study was to investigate the relationship between maternal risk factors, neonatal demographic features and asymmetric dimethylarginine (ADMA) levels in a randomly selected group ofThe aim of this study was to investigate the relationship between maternal risk factors, neonatal demographic features and asymmetric dimethylarginine (ADMA) levels in a randomly selected group of pregnancies during delivery. The subjects were categorized into five groups as having: no maternal risk factor, maternal hypertension, gestational diabetes, maternal smoking history, and meconium staining. Blood samples were taken from the mothers before delivery and from the umbilical vein after delivery. Mean ADMA levels were significantly lower in the cord blood when compared with maternal levels in all groups. Mean ADMA level of neonates in the meconium staining group was found to be significantly higher than in the other groups (p<0.001). Maternal age, delivery type, parity and sex did not show any effect on cord blood ADMA levels. Overall, umbilical vein ADMA levels are modulated independent of several maternal features and risk factors. Although these factors are interrelated and it is difficult to interpret the relevant data separately, the most significant factor affecting umbilical vein ADMA levels seems to be perinatal hypoxia as in the case of meconium staining.

• Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid

  Authors: Nadir Korkmazer, Sebahattin Vurucu, Erkan Demirkaya, Bulent Unay, Mustafa Kul, Rıdvan Akin, Erdal Gokcay

  Brain and Development.

  Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbancesValproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including anorexia and nausea, and hepatoxicity. As to its dose-dependent side effects are the weight loss, tremor, skin eruption and the alopecia. In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver biotinidase enzyme activities, serum AST, ALT, albumin, and valproic acid levels were measured. Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver biotinidase enzyme activities and the serum valproic acid levels, and the negative correlation between the liver tissues biotinidase activities and the serum valproic acid levels were noted, respectively. As a conclusion, the partial alopecia which is an initial symptom of reduced biotinidase activity may also be created depending on the reduction of biotinidase activity during valproic acid therapy. The alopecia which may further be observed in the patients receiving valproic acid therapy may be prevented by means of administration of biotin in a dose of 10 mg/day.

• Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy

  Authors: Sebahattin Vurucu, Erkan Demirkaya, Mustafa Kul, Bulent Unay, Davut Gul, Rıdvan Akin, Erdal Gokçay

  Progress in Neuro-Psychopharmacology and Biological Psychiatry.

  Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 areHomocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them.In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.

• Screening for retinopathy of prematurity in a tertiary care newborn unit in Turkey: frequency, outcomes, and risk factor analysis.

  Authors: Fatih Mehmet Mutlu, H Ibrahim Altinsoy, Tarkan Mumcuoglu, Hürkan Kerimoglu, Selim Kiliç, Mustafa Kul, S Umit Sarici, Faruk Alpay

  Journal of pediatric ophthalmology and strabismus. 45(5):291-8.

  PURPOSE: To report the frequency, risk factors, and outcomes of screening for retinopathy of prematurity (ROP). METHODS: Data of neonates with a gestational age of 34 weeks or less were analyzed andPURPOSE: To report the frequency, risk factors, and outcomes of screening for retinopathy of prematurity (ROP). METHODS: Data of neonates with a gestational age of 34 weeks or less were analyzed and the predictors on the development of ROP were determined by using logistic regression analysis. RESULTS: Of the 318 neonates, the frequency of ROP was 37.1% for any stage and 7.2% for stage 3 or greater. Treatment was needed in 16.1% of neonates with ROP. No treatment was required in neonates with a gestational age of greater than 32 weeks. Oxygen therapy, sepsis, gestational age of 32 weeks or less, and birth weight of less than 1,250 g were determined as the independent risk factors. CONCLUSIONS: Although frequency of ROP in Turkey is similar to that in the United States, the rate of severe ROP necessitating treatment seems to be higher in Turkey. Neonates with a gestational age of 32 weeks or less, a birth weight of less than 1,250 g, sepsis, and oxygen therapy may have a greater risk of developing ROP and screening should be intensified in the presence of these risk factors.