Zehra Sema Ozkan

Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia, and their relation with severity of disease

Abstract Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants. Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version. Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p < 0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p < 0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age. Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.

What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility?

Implantation necessitates complex interactions among the developing embryo, decidualizing endometrium, and developing maternal immune tolerance and/or alterations in cellular and humoral immune responses. Overstimulation of T helper 1 (Th1) or Th2 cytokines in systemic and local environments, alterations of the prevalence of IL17 and regulatory T cell (Treg) cytokines have also been suggested to contribute to the pathogenesis of implantation failure. We aimed to investigate the plasma levels of IL4, IL6, IL10, TNFα, IFNγ, TGFβ, IL17, IL35, and SOCS3 in infertile and fertile women. This case-control study was conducted with 80 women suffering from unexplained infertility and 40 fertile women. Peripheral venous blood samples were drawn on day 21 of the menstrual cycle. The extracted plasma samples were assayed by an enzyme linked immunosorbent assay. Statistical analysis was performed using SPSS version 16.0. Our main findings were as follows: despite the significantly high IL17 and IL35 plasma levels of infertile women, IL35/IL17 ratio was significantly lower in the infertile group compared with that in the fertile group; SOCS3 plasma levels showed an inverse relation with plasma levels of all cytokines except IL35; increased plasma IL17 levels (>3.42 pg/mL) have a negative impact on fertility; TNFα/IL10, IFNγ/IL10, IFNγ/IL6, and IFNγ/IL4 ratios were significantly higher in infertile group compared with those in the fertile group. It is not possible to show the major immunological factor(s) of unexplained infertility, but our findings point out that the decreased suppressor activity of the immune system may play a role in implantation failure.

Impact of intracystic ethanol instillation on ovarian cyst diameter and adjacent ovarian tissue

OBJECTIVE To investigate the regression level of simple ovarian cyst size after local ethanol application and the damage level of adjacent ovarian reserve in rats. STUDY DESIGN This study was conducted at Firat University Animal Laboratory with 18 mature (12-14 weeks old) female Wistar albino rats weighing 200-220g, with regular cycles. Ovarian cyst induction was performed with unilateral salpingectomy. Fourteen rats with ovarian cysts after a second laparotomy were divided into two groups as follows: Group 1 (n=7): cyst aspiration group, and Group 2 (n=7): intracystic 95% ethanol application group. One month after the cyst aspiration procedure a third laparotomy was performed. The cyst number and size were recorded for each rat. Right ovariectomy was performed and formalin-fixed/paraffin-embedded tissues were sectioned at 5μm thickness. Under light microscopy, ovarian total follicle reserve and fibrosis were evaluated with Masson trichrome staining and apoptosis was evaluated with TUNEL staining. The groups were compared with the Mann-Whitney U test and Wilcoxon Rank test. p<0.05 was considered significant. RESULTS Ovarian cyst formation was observed in 85% (15/18) of rats. The mean diameter of ovarian cysts in Groups 1 and 2 were, respectively, 10.3mm and 10.1mm. After aspiration, there was no significant reduction in the cyst diameter (10.3mm vs 8.1mm), but after ethanol application the diameter significantly reduced (10.1mm vs 3.4mm, p<0.05). Mean ovarian follicle count in Group 2 was significantly lower than in Group 1 (25 vs 42, p<0.05), and mean fibrosis and apoptosis scores in Group 2 were significantly higher than in Group 1 (2.5 vs 0.9, p<0.05). CONCLUSION Local ethanol application reduces cyst diameter but concomitantly decreases ovarian reserve due to increased fibrosis in rats. In humans, intracystic ethanol application should be performed cautiously.

What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Abstract Objective: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls. Methods: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay. Results: The mean age of RPL and control cases were 31.6 ± 0.6 and 32.1 ± 0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk. Conclusion: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.

Is there any relation between IL-6 gene -174 G>C polymorphism and postmenopausal osteoporosis?

OBJECTIVE IL-6 gene single nucleotide polymorphisms (SNPs) have been reported to have a protective effect against bone resorption. We aimed to investigate the association between bone mineral density and IL-6 promoter region -174 G>C SNP. STUDY DESIGN This study included 356 postmenopausal Turkish women, of whom 201 were osteoporotic (lumbar spine T score<-2.5 SD) and 155 non-osteoporotic (lumbar spine T score>-1.5 SD). Bone mineral density (BMD) measures were obtained using dual-energy X-ray absorptiometry. SNP of the IL-6 gene (-174 G>C) was examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS The frequencies of the variant C allele (24% vs. 30%, p=0.074) and mutant CC genotype (12% vs. 20%, p=0.094) were higher in non-osteoporotic women. Lumbar spine and total hip BMD values were lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype. The GG (p=0.022) and GC (p=0.037) genotypes were covariates which approached statistical significance in the regression model fitting of BMD. CONCLUSION IL-6 promoter region SNP showed an association with BMD in this postmenopausal Turkish population and these data suggest that the wild GG genotype influences the phenotype.

Our clinical experience about prenatal diagnosis and neonatal outcomes of fetal central nervous system anomalies.

Objective. To present a retrospective analysis of the prenatal diagnosis and the outcome of fetuses diagnosed with central nervous system (CNS) anomalies. Materials and methods. We reviewed the medical records and ultrasound data of 69 cases diagnosed with CNS anomalies from 2007 to 2008. We described the prenatal diagnosis, associated findings, and outcome of these patients. Results. Sixty-nine patients were diagnosed with CNS anomalies. Of these, 31 had ventriculomegaly + hydrocephaly, 14 had spina bifida + meningomyelosel, 5 had choroid plexus cyst, 5 had Dandy Walker malformation, 3 had sacrocoxigeal teratoma, 2 had encephalosel, 1 had microcephaly, and 1 had Arnold Chiari malformation. Eight amniocentesis, three cord blood sampling, and two fetal reduction procedure were performed. Nine pregnancy termination and 36 delivery were performed. Neurosurgical correction was performed for neonates with spina bifida, hydrocephaly and sacrocoxigeal teratoma. Twenty-one neonates were discharged with cure, 4 neonates with follow-up, 7 neonates with paraplegia, and 13 neonates died. Conclusion. The outcome of fetuses with CNS anomalies was shown to depend mainly on the degree of neural tube defect and the associated anomalies were the most important factors in surviving.

Heterotopic pregnancy following bilateral tubal ligation: Case report

ABSTRACT Case report A 38-year-old woman presented, one year after bilateral tubal ligation, with vaginal bleeding, vomiting, and stupor. Ten days earlier, she had submitted to a dilatation and curettage for an unexpected intrauterine pregnancy. At the time of this presentation there was rebound tenderness and guarding on abdominal examination, and a 2.5 cm right adnexal mass was detected on transvaginal ultrasound together with free fluid in the pelvis. The serum level of beta-hCG was 8522 mIU/ml. At laparoscopy a right tubal pregnancy and a large haematocele in the pouch of Douglas were detected. A right salpingectomy and a bipolar electrocoagulation of the left tubo-cornual junction were performed laparoscopically. Conclusion Pregnancy after tubal sterilisation may be heterotopic and this possibility should be considered in the differential diagnosis.

Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study.

Objective To examine the effects of low-to-high doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome (OHSS) in an experimental setting. Materials and methods A total of 20 female Wistar albino rats, 22 days of age, were randomly divided into four groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15 rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2 (n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3 mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats. Kruskal–Wallis variance analysis and the Mann–Whitney U-test were used for statistical comparisons. A Bonferroni correction was performed to control the inflation of significance, with a significance level set at a P-value of less than 0.025. Results Despite higher serum VEGF, endothelin 1, follicular reserve, and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to controls, these differences were not significant (P>0.025, Mann–Whitney U-test). There was a significant reduction in the ovarian follicular reserve in tamoxifen groups compared to controls (P<0.025, Mann–Whitney U-test), while angiogenesis of the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were significantly higher in rats receiving tamoxifen (P<0.025, Mann–Whitney U-test). Also, significantly lower follicular reserve and fibrosis were observed among rats in the low-dose tamoxifen group in comparison with rats in the high-dose tamoxifen group (P<0.025, Mann–Whitney U-test). No groups had a significant change in endothelin 1 levels (P>0.025, Mann–Whitney U-test). Conclusion Tamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and endothelin 1 levels, and ovarian follicle reserves were significantly reduced in our experimental model.

Impact of grandmultiparity on perinatal outcomes in eastern region of Turkey.

Abstract Objective: It is suggested that grandmultiparity is a troublesome condition in obstetric settings because of increased perinatal complications. Our objective was to compare the incidence of antenatal and intrapartum complications and perinatal outcomes among women who had delivered ≥5 times (grandmultiparous) with those of women who had delivered 1–4 times (parous). Method: A retrospective study was conducted in a university hospital. The study population consisted of age-matched 249 grandmultiparous women and 338 parous women, who had delivered between January 2008 and January 2011. Maternal case records were retrieved and analyzed from the labor ward records. Statistical analysis was done using SPSS version 14.0; χ2 test was used to analyze categorical variables. Results: The frequencies of hypertensive disorders and gestational diabetes mellitus did not differ between gropus (p > 0.05). Obstructed labor, cord prolapse, placenta previa and abruptio placenta were higher in grandmultiparous women. A significantly higher rate of cesarean deliveries was observed in the study population. There was no difference in terms of mode of delivery, prevalence of low and high birthweight (<2.5 and >4 kg) babies, stillbirth, multiple pregnancy and fetal distress. Conclusions: We did not observe an increased incidence of perinatal complications in grandmultiparous women.

Coexistence of adenomyosis in women operated for benign gynecological diseases

Background: To compare demographic, clinical and histopathological characteristics of women diagnosed with adenomyosis (AG) after hysterectomy to those of women diagnosed with leiomyoma (LG) and to investigate the predisposing factors for AG. Methods: This study was carried out on 204 patients who underwent gynecologic surgery for various indications except for gynecologic malignancy between January 2005 and December 2009 and whose histopathological analysis of hysterectomy/myomectomy specimen revealed either AG or LG. Women with AG and those with LG were compared with respect to age, parity, menstrual pattern, history of induced abortion, history of prior uterine surgery, smoking, dysmenorrhea, dyspareunia, chronic pelvic pain and coexisting endometrial and ovarian pathologies. Results: The mean age of our patients was 51 ± 8 years (range 28–85), 40% of them were postmenopausal, and 64% had a history of uterine surgery. The mean age (p = 0.014), gravida (p = 0.018), parity (p = 0.017) and previous endometrial sampling (p < 0.01) were significantly higher in AG. Main symptoms were abnormal uterine bleeding (39%), dysmenorrhea (63%) and nonmenstrual pelvic pain (62%). Age (p = 0.01), menometrorrhagia (p = 0.02) and endometrial sampling (p < 0.01) were the significant covariants in binary logistic regression for AG. Conclusion: AG is an enigmatic disease frequently causing gynecologic complaints and endomyometrial junction deterioration during endometrial sampling may be a trigger point for developing AG.