Huray Islekel

Aim: IDH mutations have been identified as frequent molecular lesions in several tumor types, particularly in gliomas. As a putative marker of IDH mutations, elevated D-2-HG has been reported in gl...

To analyze the clinical and laboratory factors that potentially affect the diagnosis-to-delivery time in preeclamptic pregnancies.

Objective: The aim of this study was to investigate serum and tissue levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) and to evaluate correlations between serum and tissue parameters with respect to clinicopathological features in patients with lung cancer. Methods: The study was conducted on 34 patients with stage I-IV primary lung cancer and 32 healthy controls. Preoperative serum, tumor and matched normal tissue VEGF, Ang-1 and Ang-2 levels were determined with ELISA. Results: Serum Ang-2 levels were significantly increased in lung cancer patients (p<0.001). VEGF levels were significantly higher in tumor tissue than in matched normal tissue (p<0.001). Ang-1 and Ang-2 levels were significantly higher in normal tissue than in tumor tissue (p<0.001). A significant negative correlation was found between normal lung tissue Ang-2 and serum VEGF levels (r=−0.400, p=0.019). A significant correlation was observed between serum and lung tissue Ang-2 levels (r=0.397, p=0.020). Conclusion: This study clearly demonstrated that VEGF, Ang-1 and Ang-2 are all involved in lung cancer process. This was the first study to show a correlation between serum and tissue levels of Ang-2 in lung cancer. This finding might be the basis for therapeutic strategies against lung cancer.

Objective: The objective of the study is to assess the predictive power of mean uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF) and placenta associated plasma protein A levels for the development of ischemic placental diseases (IPD) in a cohort of unselected singleton pregnancies during the first trimester combined test period.Materials and Methods: A sample of 880 pregnancies was registered between September 2014 and January 2016. After routine examination for first trimester combined test, UtA PI was measured, and maternal serum was obtained and stored at −80 °C for PlGF assessment.Results: Early‐onset preeclampsia, late‐onset preeclampsia and placental dysfunction‐related fetal growth restriction were observed in 6 (0.7%), 17 (2.0%) and 27 (3.2%) cases, respectively. IPD requiring delivery before 34 weeks of gestation could be predicted with a sensitivity, specificity, positive predictive value and negative predictive value of 76.2%, 90.2%, 20.2% and 99.1%, respectively.Conclusion: A combination of UtA PI, placenta associated plasma protein A and PlGF was proven to be successful in the first trimester prediction of IPD, with the highest sensitivity in the subgroup who required delivery before 34 weeks of gestation. In reducing the number of pregnancies that should be followed‐up, further studies for new biomarkers are needed. © 2017 John Wiley & Sons, Ltd.

The identification of early markers of atopy in cord blood of newborns at delivery may offer prediction of future allergic sensitization. The aim of this study was to evaluate the relationship between cord blood interleukin-13 (IL-13) and interferon-gamma (IFN-γ) and development of allergic diseases during the first five years of life. Umbilical cord blood samples were collected at the time of delivery from 62 newborns. The families of these newborns were asked to complete a questionnaire about age and education of parents, number of siblings, allergic diseases in family members, cigarette exposure during pregnancy and presence of pets in their house. The same subjects were evaluated when they were five years old. Venous blood samples were drawn and epidermal skin prick tests were performed. IL-13 and interferon-gamma (IFN-γ) levels were studied from the blood samples which were taken during birth and five years later. There was no significant relationship between gender, type of delivery, educational levels of parents, exposure to cigarette smoke, atopy in parents, presence of pets in the house and IL-13 and IFN-γ levels in cord blood and at five years. Higher levels of IL-13 in newborns and five years olds, were found significantly related to skin prick test positivity (p=0.004 and p<0.0001, respectively) and presence of allergic diseases (p= 0.008 and p= 0.001, respectively). Levels of IFN-γ, both in cord blood and five years after, were not related with the future of allergic status of children. Higher levels of IL-13 in cord blood may be a predictor of future development of allergic sensitization.

Aim: To evaluate the significance of the cord blood ischemia‐modified albumin (IMA) level as a diagnostic marker for perinatal asphyxia and to determine the associations of IMA levels with the complexity of pregnancy and abnormal Doppler findings, regardless of perinatal asphyxia.Methods: This prospective study included 169 newborns, sixteen of whom had perinatal asphyxia and 33 who were from complicated pregnancies. Doppler measurements were obtained from the uterine, umbilical and middle cerebral arteries, and the cerebro/placental ratio (C/P). IMA was measured by means of commercially available ELISA kits and was expressed as picomoles per milliliter.Results: Ischemia‐modified albumin levels were significantly higher in neonates of complicated pregnancies as compared to uncomplicated pregnancies (P < 0.0001). They were higher in newborns with perinatal asphyxia as compared to healthy controls (P = 0.015). The C/P ratio‐pulsatility index (PI) showed a significant difference between normal and complicated pregnancies without perinatal asphyxia (P < 0.0001). IMA levels were significantly increased in cases with abnormal C/P ratio‐PI.Conclusions: Elevated cord blood IMA levels may be accepted as a useful marker in perinatal asphyxia. Abnormal Doppler examinations are associated with elevated IMA levels in complicated pregnancies.

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

Endothelial cells lining the inner blood vessel walls play a key role in the response to hypoxia, which is frequently encountered in clinical conditions such as myocardial infarction, renal ischemia and cerebral ischemia. In the present study we investigated the effects of hypoxia and hypoxia/reoxygenation on gelatinases (matrix metalloproteinase-2 and -9), their inhibitor (TIMP-2) and activator (MT1-MMP), in human umbilical vein endothelial (HUVE) cells. HUVE cells were subjected to 4 h of hypoxia or hypoxia followed by 4 and 24 h of reoxygenation. The pro- and active forms of MMP-2 and MMP-9 were analyzed by gelatin zymography; TIMP-2 protein level was assayed using ELISA, while MT1-MMP activity was measured using an activity assay. The secretion of MMP-2 proform increased significantly in cells subjected to 4 h of hypoxia followed by 4 or 24 h of reoxygenation, compared with the normoxic group. TIMP-2 protein level also increased significantly in the hypoxia/reoxygenation groups, compared with the normoxic group. There were no statistically significant differences in the levels of active MT1-MMP in all groups. This study indicates that MMP-2 and TIMP-2 could be regarded as important components of a mechanism in the pathophysiology of ischemic injury following reperfusion.