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    All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis
    (Karger, 2013) Ozdemir, Ramazan; Yurttutan, Sadik; Sari, Fatma Nur; Oncel, Mehmet Yekta; Erdeve, Omer; Unverdi, Hatice Germen; Uysal, Bulent
    Background: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. Objectives: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4 degrees C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. Results: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-alpha levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001). Conclusions: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties. Copyright (c) 2013 S. Karger AG, Basel
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    Beneficial effects of Etanercept on experimental necrotizing enterocolitis
    (Springer, 2014) Yurttutan, Sadik; Ozdemir, Ramazan; Canpolat, Fuat Emre; Oncel, Mehmet Yekta; Unverdi, Hatice Germen; Uysal, Bulent; Erdeve, Omer
    Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-alpha, interleukin-1 beta, and malondialdehyde were higher in the placebo group compared to the Etanercept group. Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-alpha and interleukin-1 beta.
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    Colchicine Protects against Hyperoxic Lung Injury in Neonatal Rats
    (Karger, 2012) Ozdemir, Ramazan; Yurttutan, Sadik; Talim, Beril; Uysal, Bulent; Erdeve, Omer; Oguz, Serife Suna; Dilmen, Ugur
    Background: Bronchopulmonary dysplasia (BPD) is characterized by inflammation, fibrosis and mucosal necrosis, which leads to emphysematous coalescence of alveoli. Objective: We tested whether prophylaxis with colchicine, an anti-inflammatory, antioxidant and antifibrotic drug, would decrease the severity of lung injury in an animal model of BPD. Methods: Twenty-five rat pups were divided into three groups: control (n = 8), hyperoxia (n = 7), and hyperoxia + colchicine (n = 10). The hyperoxia groups were exposed to >95% oxygen from day 1 to 10 of life. On day 10, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Lung morphology was assessed by the mean linear intercept (MLI), a measure of alveolar size. The degree of lung inflammation and antioxidant capacity were assessed by quantifying lung homogenate tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), malondialde-hyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Results: Colchicine significantly decreased lung damage as determined by the MLI in the c groups (p < 0.01). The median level of lung MDA was significantly higher in the hyperoxia group compared with the control group (p < 0.05) and the colchicine-treated group (p < 0.05). Lung homogenate SOD and GSH-Px activities in the colchicine-treated group were significantly higher than in the hyperoxia group (p < 0.05). Furthermore, colchicine-treated pups had lower lung homogenate TNF-alpha and IL-1 beta levels compared with the hyperoxia group (p < 0.05). Conclusions: Colchicine has favorable effects on alveolarization as well as inflammation and oxidative stress markers in an animal model of BPD. Copyright (C) 2012 S. Karger AG, Basel
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    Combined (dual) drug therapy for the treatment of patent ductus arteriosus: last approach prior to ligation
    (Cambridge Univ Press, 2023) Deveci, Mehmet F.; Kaya, Huseyin; Yurttutan, Sadik; Alagoz, Meral; Gokce, Ismail K.; Karakurt, Cemsit; Gullu, Ufuk U.
    Objective: We aimed to evaluate the efficacy of combined (ibuprofen+paracetamol) medical therapy in cases of persistent haemodynamically significant patent ductus arteriosus that are resistant to standard medical monotherapy (ibuprofen and/or paracetamol) in this retrospective multi-centre study. Methods: The combined therapy included the administration of 15mg/kg/dose of paracetamol every 6 h for 3 days and ibuprofen at an initial dose of 10mg/kg/dose followed by 5 mg/kg/dose every 24 h. After 2 days following the administration of the last dose, the researchers evaluated the efficacy of combined treatment by conducting an echocardiographic examination. Results: Of all 42 patients who received combined therapy, 37 (88.1%) patients exhibited closure of the haemodynamically significant patent ductus arteriosus without requiring surgical ligation. Patients who did not respond to combined therapy had a higher mean birth weight and gestational age compared to those who responded (p < 0.05). Conclusion: The researchers believe the success of ibuprofen and paracetamol in haemodynamically significant patent ductus arteriosus treatment may be due to their synergistic efficacy and inhibition of the prostaglandin synthesis pathway through different enzymes. The results of our retrospective trial suggest that combination therapy with paracetamol and ibuprofen can be attempted when monotherapy is unsuccessful in treating haemodynamically significant patent ductus arteriosus, especially in centres without a surgical department.
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    Effect of partially hydrolyzed synbiotic formula milk on weight gain of late preterm and term infants-a multicenter study
    (Frontiers Media Sa, 2023) Sahin, Suzan; Buyuktiryaki, Mehmet; Okur, Nilufer; Akcan, Abdullah Baris; Deveci, Mehmet Fatih; Yurttutan, Sadik; Gunes, Sezgin
    Introduction: Data on the effectiveness of hydrolyzed infant formula containing both pre- and probiotics (synbiotic formula) on the growth of infants is still scarce. This retrospective study was designed to evaluate the effect of a partially hydrolyzed synbiotic formula on growth parameters and the possible occurrence of major gastrointestinal adverse events or morbidities in infants born via cesarean section (C-section) delivery.Methods: C-section-delivered term and late preterm infants who received either partially hydrolyzed synbiotic formula, standard formula, or maternal milk and followed at seven different hospitals from five different regions of Turkey, during a 1-year period with a minimum follow-up duration of 3 months were evaluated retrospectively. All the included infants were evaluated for their growth patterns and any kind of morbidity such as diarrhea, constipation, vomiting, infection, or history of hospitalization.Results: A total of 198 infants (73 in the human milk group, 61 in the standard formula group, and 64 in the partially hydrolyzed synbiotic formula group) reached the final analysis. The groups were similar regarding their demographic and perinatal characteristics. No difference was observed between the three groups regarding gastrointestinal major side effects. Growth velocities of the infants in the human milk and partially hydrolyzed synbiotic formula groups during the first month of life were similar whereas the weight gain of infants in the standard formula group was significantly less than these two groups (p < 0.001). Growth velocities were similar among the three groups between 1st and 3rd months of age.Discussion: A partially hydrolyzed synbiotic formula provided better weight gain in late-preterm and term infants who were delivered via C-section delivery compared to the standard formula during the first month of life. This weight gain was similar to the infants receiving exclusively human milk. This difference was not observed in length and head circumference gain. No difference was observed in any of the parameters during the 1st-3rd months of age. Specially formulated partially hydrolyzed synbiotic formulas may reverse at least some of the negative impacts of C-section delivery on the infant and help to provide better growth, especially during the early periods of life.
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    Is Folic Acid Supplementation Really Necessary in Preterm Infants ?32 Weeks of Gestation?
    (Lippincott Williams & Wilkins, 2014) Oncel, Mehmet Yekta; Calisici, Erhan; Ozdemir, Ramazan; Yurttutan, Sadik; Erdeve, Omer; Karahan, Sevilay; Dilmen, Ugur
    Objectives: The aim of this study was to define whether there was folate deficiency in hospitalized preterm infants, and, second, to define the effect of feeding modalities on serum folate levels. Methods: Infants born <= 32 weeks of gestation were included in the study. Blood samples for the determination of serum folate levels were obtained on days 14 and 28 postnatally, as well as 36 weeks postconceptionally (or just before discharge if patients are discharged <36 weeks)-samples A, B, and C, respectively. Infants were divided into 3 groups based on mode of feeding; human breast milk (HBM), fortified HBM (fHBM), or preterm formula (PF). Results: A total of 162 preterm infants were enrolled: 17 (10.5%) of whom received HBM alone, 94 (58%) received fHBM, and 51 (31.5%) were fed with PF. None of the preterm infants developed folate deficiency during the study period. Preterm infants in the fHBM and PF groups had significant higher serum folate levels in samples C when compared with those receiving HBM alone (P < 0.001 for both). Multivariate analysis to evaluate the effects of maternal supplementation, smoking habit, gestational age, birth weight, and cumulative folic acid intake in samples A, B, and C suggested that maternal smoking and maternal folic acid supplementation had significant effects on serum folate levels in sample A and B. Conclusions: Preterm infants receiving parenteral nutrition with high folic acid content have no risk of folate deficiency during the 2 months of age; however, preterm infants fed orally from birth with HBM or PF with a low folic acid content could be at risk for folate deficiency, especially when mothers are smokers and/or do not receive folic acid supplementation during pregnancy.
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    Mean Platelet Volume in Neonatal Sepsis
    (Wiley, 2012) Oncel, Mehmet Yekta; Ozdemir, Ramazan; Yurttutan, Sadik; Canpolat, Fuat Emre; Erdeve, Omer; Oguz, Serife Suna; Uras, Nurdan
    Background The aim of this study was to investigate any changes in mean platelet volume (MPV) in patients with neonatal sepsis (NS). Methods Subjects were stratified into two groups: proven sepsis (Group 1a) and clinical sepsis (Group 1b). The control group (Group 2) consisted of healthy newborns matched for gestational age and birth weight. Results A total of 100 patients with NS (35 with proven sepsis and 65 with clinical sepsis) and 50 healthy controls were enrolled. A comparison of markers of sepsis obtained at baseline revealed white blood cell count (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), and MPV levels to be significantly higher in newborns with sepsis compared to healthy controls (P = 0.01, <0.001, <0.001, and 0.001, respectively). Mean baseline serum levels of CRP and MPV were significantly higher in Group 1a compared to Group 1b (P = 0.003, P = 0.007, respectively), whereas the difference between group with regards to baseline serum levels of IL-6 and platelet count was statistically insignificant (P = 0.14, P = 0.28, respectively). Conclusion This is the first study to demonstrate a statistically significant difference with regard to baseline MPV values between patients with sepsis (proven or clinical) and healthy controls. J. Clin. Lab. Anal. 26:493-496, 2012. (C) 2012 Wiley Periodicals, Inc.
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    The relationship between trough drug concentrations and ductal closure in preterm infants treated with three-dose-oral ibuprofen
    (Taylor & Francis Ltd, 2013) Yurttutan, Sadik; Erdeve, Omer; Oncel, Mehmet Yekta; Ozdemir, Ramazan; Dilmen, Ugur
    The aim of the present study was to characterize the pharmacokinetic profile of oral ibuprofen on consecutive 3 d by trough serum levels, and if possible to define a cut-off level for ductal closure in preterm infants. The study enrolled 20 preterm infants with gestational age <= 30 weeks, birth weight <1250 g and hemodynamically significant patent ductus arteriosus (hsPDA). Patients received oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. Patients were compared for serum ibuprofen levels in addition to their demographic and clinical data in case of their response to the treatment. hsPDA closed in 16 (80%) of the patients. Although mean ibuprofen levels on consecutive 3 d showed a plateau in general, ibuprofen serum levels on the first treatment day were statistically low in patients with unclosed hsPDA (p = 0.003). The optimal cut-off value for serum ibuprofen level on the first treatment day was measured as 5.5 mg/l with 100% sensitivity and 93% specificity. Serum ibuprofen level on the first treatment day seems to be an important factor for a successful ductal closure. Target concentration approach by the evaluation of trough level may be applicable to real-time dosing strategy.