Nuray Bozkurt

Role of Oxidative Stress in Intrauterine Growth Restriction

Aims: The objectives of this study were to determine the role of oxidative stress in intrauterine growth restriction (IUGR) and to investigate the possible molecular mechanism(s) leading to oxidant stress in IUGR. Methods: Parameters of the oxidative and antioxidant system were evaluated in maternal plasma, umbilical cord blood, and placental tissue of pregnant women with IUGR fetuses. The same samples were obtained from women with normal pregnancies and were evaluated. Results: The results of this study indicate that while the levels of malondialdehyde (MDA) and xanthine oxidase (XO) were higher in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR when compared to the control group [MDA: 142.8 ± 18.0 vs. 86.4 ± 22.5 nmol/ml, 151.6 ± 25.8 vs. 93.3 ± 7.4 nmol/ml, and 0.72 ± 0.19 vs. 0.42 ± 0.09 nmol/mg protein, respectively (for all p < 0.0005); XO: 1.251 ± 0.674 vs. 0.20 ± 0.019 mIU/ml (p < 0.0005), 1.97 ± 0.73 vs. 0.237 ± 0.143 mIU/ml (p < 0.0005), and 0.023 ± 0.0012 vs. 0.012 ± 0.004 mIU/ml (p < 0.025), respectively], the levels of antioxidant potential were identified to be lower in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR: 63.3 ± 11.9 vs. 198.0 ± 31.9 U/ml (p < 0.0005), 32.6 ± 3.7 vs. 206.5 ± 27.1 U/ml (p < 0.0005), and 0.56 ± 0.23 vs. 1.16 ± 0.29 U/ml (p < 0.0005), respectively. On the other hand, the activities of adenosine deaminase of the IUGR patients were higher than those of the control group in maternal plasma (204.8 ± 103.5 vs. 115.6 ± 31.8 U/l, p < 0.01) and umbilical cord blood samples (584.2 ± 285.2 vs. 147.9 ± 44.8 U/l, p < 0.0005) which may suggest that oxidative stress has a role in IUGR. Moreover, an increased superoxide dismutase activity in maternal plasma (128.2 ± 37.4 vs. 88.8 ± 16.6 U/ml, p < 0.005) and cord blood (162.1 ± 37.0 vs. 116.6 ± 20.7 U/ml, p < 0.005) and an increased glutathione peroxidase activity in maternal plasma (1.83 ± 0.26 vs. 1.47 ± 0.31 IU/ml, p < 0.01) and placental tissue (0.007 ± 0.0015 vs. 0.003 ± 0.0012 IU/ml, p < 0.0005) were detected, while decreased catalase activities in cord blood (23,717 ± 3,538 vs. 16,397 ± 2,771 IU/ml, p < 0.0005) and placental tissue (47.2 ± 17.2 vs. 70.7 ± 11.3 IU/ml, p < 0.005) were identified in IUGR groups. Conclusions: In the light of the results of this study, it can be stated that the oxidative stress increases in patients with IUGR. Providing high-risk patients with an antioxidant may be useful in the prevention or treatment of IUGR, although it is a condition with no certain treatment outcome.

Circulating concentrations of adiponectin and tumor necrosis factor-α in gestational diabetes mellitus

Adiponectin and tumor necrosis factor-α (TNF-α) have been implicated in insulin resistance and diabetes mellitus (DM). In the present study we investigated levels of adiponectin and TNF-α and their relationships with each other and metabolic factors in women with gestational DM (GDM). Thirty-four pregnant women with GDM and 31 pregnant women with normal glucose tolerance (NGT) were included in the study. Plasma adiponectin levels were lower in GDM than in NGT (36.9 ± 6.7 vs. 61.3 ± 13.0 ng/ml, p = 0.028). Serum TNF-α levels were increased in GDM compared with NGT (20.5 ± 2.4 vs. 14.0 ± 1.5 pg/ml, p = 0.042). After adjustment for pre-pregnancy and current body mass index (BMI), adiponectin levels correlated negatively with insulin resistance by homeostasis model assessment-insulin resistance (HOMA-IR) and 0-h and 1-h glucose both at glucose challenge test and oral glucose tolerance test in GDM. Adiponectin levels were correlated only with very low-density lipoprotein cholesterol and triglyceride levels in NGT. TNF-α levels were correlated with glycated hemoglobin in GDM. There was a significant positive correlation between TNF-α levels and pre-pregnancy and current BMI in GDM as well as NGT. HOMA-IR for adiponectin and pre-pregnancy BMI for TNF-α remained as significant determinants in multiple regression analyses. In conclusion, these data suggest that reduced adiponectin and increased TNF-α may be involved in the pathogenesis of GDM.

Comparison of transvaginal ultrasonography and saline infusion sonohysterography in evaluating the endometrial cavity in pre- and postmenopausal women with abnormal uterine bleeding.

Objective:To compare the diagnostic accuracy of transvaginal ultrasonography (TVUS) and saline infusion sonohysterography (SIS) of the endometrial cavity in pre- and postmenopausal women with abnormal uterine bleeding. Design:In a prospective study, TVUS and concurrent SIS findings of 100 pre- and 33 postmenopausal women were recorded. The pathological diagnoses of the specimens, obtained by means of dilatation and curettage, hysteroscopy, and hysterectomy, were taken as reference and compared with the results of TVUS and SIS. Results:When TVUS and SIS findings were compared with pathological results, the sensitivity and specificity of TVUS in diagnosing endometrial pathologies were 83% and 70.6%, respectively, whereas the sensitivity and specificity of SIS were 97.7% and 82.4%, respectively. The sensitivity and specificity of SIS in the diagnosis of endometrial polyps were 100% and 91.8%, respectively, and in the diagnosis of fibroids were 95% and 100%, respectively. Conclusion:SIS is more accurate than TVUS alone in the evaluation of the endometrial cavity in women with abnormal uterine bleeding.

The mean platelet volume in gestational diabetes

AbstractObjective: To compare the platelet count and mean platelet volume (MPV) values of pregnancies diagnosed with gestational diabetes with those of healthy pregnancies. Material—method: Between June 2003 and September 2004, 100 healthy pregnancies and 100 pregnancies with gestational diabetes were studied at Gazi University, Department of Obstetrics and Gynecology. Results: While no statistically significant difference was observed in the platelet count between the two groups, the MPV of the gestational diabetes group (9.4 ± 1.6 fl) was evaluated to be significantly higher than the MPV of the healthy pregnancy group (8.3 ± 1.1 fl). Additionally, when linear regression analysis was performed an inverse relationship was observed between platelet number and MPV. Conclusion: There is a need for further research focusing on the platelet function in the observation and treatment of gestational diabetes, which can pose the risk of developing Type 2 diabetes for the mother and has negative consequences for the fetus.

The relationship of homocyteine, B12 and folic acid with the bone mineral density of the femur and lumbar spine in Turkish postmenopausal women

ObjectiveThe relationship of homocyteine, B12 and folic acid with osteoporosis has already been studied in various populations. We compared the important factors in the metabolism of homocysteine, such as homocysteine, B12 and folic acid levels, of Turkish postmenopausal women, and their relationship with the femur and lumbar spine bone mineral density.MethodsThis cross-sectional study was conducted at Gazi University, Department of Obstetrics and Gynecology. The study group consisted of 178 postmenopausal women. Serum homocysteine, folic acid and Vitamin B12 were measured. BMD was measured using DEXA at the right femoral neck and lumbar spine (L1–L4).ResultsUpon evaluation of both the femur and lumbar spine, it was determined that osteoporosis could be associated with a homocysteine level above the median and with a B12 value under the lowest quintile value.ConclusionPlasma Hcy and vitamin B12, but not folate levels, were associated with osteoporosis. Future interventional studies are needed to determine methods to reduce Hcy levels with dietary supplements and extra vitamin B12, which will restore bone health and reduce risk of fractures.

The role of frozen section evaluation in the diagnosis of adnexal mass

The purpose of this study was to evaluate the accuracy of frozen section diagnosis in patients who were subjected to the exploratory laparotomy for pelvic mass. Overall, 207 patients were included in this study and the mean age of the patients was 50.9 ± 14.9 years (range, 18–84 years). Of these patients, 98 (47%) had benign, 16 (8%) had borderline, and 93 (45%) had malignant histologies at permanent section. The diagnosis at frozen section was deferred for three patients (1.4%) and these patients were excluded from the further analyses. The overall discordance rate was 5.3%. To calculate the sensitivity and specificity values, 2 × 2 contingency tables were constructed in two ways. In the first calculation, borderline histology was considered malignant, and the sensitivity and specificity rates were 97% and 92%, respectively. In the second analysis, it was accepted as benign, and these values were 100% and 98%, respectively. To determine the possible factors related with discordant diagnoses, age, menopausal status, tumoral size, laterality of tumors, and histologic diagnoses were analyzed. Significant association was noted for size and borderline and mucinous histologies. In patients with borderline histology, the discordance rate was 40%. This value for the remaining patients was 3.2% (P< 0.001). The rate of misdiagnosis was 17.4% for mucinous tumors, whereas it was 4.8% for the remaining epithelial tumors (P= 0.03). Frozen section evaluation revealed high sensitivity and specificity values in this study. To increase the accuracy of diagnosis, further diagnostic markers are needed especially for patients with large lesions, borderline tumors, and mucinous histologies.

Investigation of free radical scavenging enzyme activities and lipid peroxidation in human placental tissues with miscarriage.

Background: Miscarriage (early pregnancy failure) is a pregnancy-related disease, the pathophysiology of which is still not completely understood. Lipid peroxidation and alterations in antioxidant enzyme activities may be of importance in the pathogenesis of this disorder. This study was planned to investigate the possible relation between free radical scavenging enzyme activities and lipid peroxidation levels in placenta tissues with miscarriage. Methods: Placental tissue samples were obtained from 21 patients who had miscarried and 25 normal pregnant women undergoing elective abortion as a control group. Total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities and levels of thiobarbituric acic reactive substances (TBARS), antioxidant potential (AOP), and nonenzymatic superoxide radical scavenger activity (NSSA) were measured in the placental tissues. Results: GSH-Px, CAT activities, and TBARS levels were found to be significantly increased, while T-SOD and NSSA values decreased in patients with early pregnancy failure when compared with women undergoing elective abortion (control group). However, there were no significant differences in AOP levels between the groups. Conclusions: Our results reflects oxidative stress in placenta tissues of early pregnancy failure, as the oxidative processes seem to be counteracted by the physiologic activation of antioxidant enzymes such as CAT and GSH-Px. Moreover, a compensatory mechanism might be developed against possible oxidative damage in patients with miscarriage.

Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells

OBJECTIVE To analyze the association of micro-ribonucleic acid (miRNA) expression with the number of oocytes retrieved, in women undergoing in vitro fertilization (IVF). DESIGN Experimental study. SETTING Academic medical center. PATIENT(S) A total of 189 women undergoing IVF-intracytoplasmic sperm injection (ICSI). INTERVENTION(S) Pooled cumulus cells were collected. MAIN OUTCOME MEASURE(S) Poor responders were identified as patients who produced fewer oocytes than the 25th percentile of their respective age group. MicroRNAs were extracted from cumulus cells, and an miRNA microarray was performed, comparing poor responders (n = 3) to non-poor responders (n = 3). Expression of miR-21-5p (active strand of miR-21) and miR-21-3p was tested in poor responders (n = 21) and non-poor responders (n = 29), using reverse transcription real-time polymerase chain reaction (qRT-PCR). Regulation of miR-21-5p and miR-21-3p, in human granulosa-like tumor (KGN) cells, by estradiol (E2), was tested in vitro. RESULT(S) MicroRNA microarray analysis showed up-regulation of 16 miRNAs and down-regulation of 88 miRNAs in poor responders. Notably, miR-21 was significantly up-regulated 5-fold in poor-responder samples. Analysis using qRT-PCR confirmed that miR-21-5p expression was significantly up-regulated in poor responders, whereas miR-21-3p expression was significantly lower, suggesting that elevated miR-21-5p expression in cumulus cells is not regulated at the pre-miR-21 level in poor responders. Both miR-21-5p and miR-21-3p were increased in KGN cells in response to higher doses of E2; their expression was not affected at lower E2 concentrations. CONCLUSION(S) We found that poor response to IVF is associated with altered miRNA expression in cumulus cells, specifically with elevated expression of miR-21-5p, and that this elevated expression is independent of lower serum E2 levels in poor responders.

Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the significance of preoperative platelet counts in advanced epithelial ovarian cancer with respect to second-look laparotomy results and disease progression. METHODS: We prospectively evaluated 37 consecutive patients with advanced epithelial ovarian cancer who underwent primary surgical treatment. In addition to platelet counts, all patients were evaluated with respect to age, gravida, parity, and stage and grade of tumor. Thirty-six patients had stage III, and 1 patient had stage IV disease. Optimal debulking (diameter of residual tumor, less than 1 cm) was performed in all patients who subsequently received adjuvant chemotherapy (platin-paclitaxel). According to second-look laparotomy and follow-up results patients were divided into 2 groups. The first group had negative second-look laparotomy or no evidence of disease during follow-up (n = 20), and the second group had positive second-look laparotomy or progressive disease (n = 17). Sensitivity and specificity values were calculated for different cutoff values of platelet counts with receiver operating characteristic curve analysis. RESULTS: Age, gravida, and parity were not significantly different compared with controls (P > .05). Mean platelet counts were 371 × 109/L and 446 × 109/L in the first and second groups, respectively (P = .03). Different cutoff values of platelet counts for the diagnosis of thrombocytosis were evaluated. A cutoff value of 380 × 109/L had sensitivity 77% and specificity 60% for recurrence, whereas a cutoff value of 400 × 109/L had sensitivity 59% and specificity 65%. Area under the curve (± standard error) was 0.72 ± 0.08 (P = .026). CONCLUSION: In patients with progressive disease and positive second-look laparotomy, preoperative platelet counts were significantly higher compared with patients with no evidence of disease on follow-up. LEVEL OF EVIDENCE: II-2

Antioxidant enzyme activities and lipid peroxidation in preeclampsia

Oxidative stress and uncontrolled lipid peroxidation are considered to be key events in preeclampsia. The aim of this study was to elucidate the relation between superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and xanthine oxidase (XO) enzyme activities and levels of thiobarbituric acid reactive substance (TBARS) parameters that were measured in maternal plasma, umbilical cord plasma and placental tissues of patients with preeclampsia and those having a healthy pregnancy [1]. Human placental tissues, fasting maternal blood and cord blood were obtained from 13 patients with preeclampsia and 13 healthy pregnant women at Gazi University Medical School Department of Obstetrics and Gynecology. Some characteristics of the subjects studied are summarized in Table 1. Results are illustrated in the Table 2. SOD activities and TBARS levels increased while GSH-Px activities decreased in maternal blood and GSH-Px and CAT activities decreased. However, TBARS levels increased in cord blood of preeclamptic cases when compared with the healthy pregnancies. Moreover, SOD and CAT enzyme activities decreased while GSH-Px activities increased in preeclamptic placentae. Also, maternal plasma, umbilical cord plasma and placental tissue XO activities increased in preeclamptic cases. Reduced uteroplacental flow in preeclampsia leads to placental hypoxia and oxidative stress. SOD, GSH-Px and CAT are antioxidant enzymes responsible for the defense against oxidative tissue damage [2]. In this study, SOD levels showed a decline in placentae of preeclamptic women. Our results are consistent with the literature as GSH-Px is concerned. In the study mentioned, CAT levels decreased both in maternal, cord plasma and placental tissues of preeclamptic patients when compared with the healthy pregnancy control group. This might result from elevated free radicals suppressing GSH-Px and CAT activities in patients with preeclampsia. XO is an integral mediator of reactive oxygen species generation. XO increases in maternal, cord plasma and placental