A potential role of Sirtuin3 and its target enzyme activities in patients with ovarian endometrioma.

OBJECTIVE: Sirtuin3 (SIRT3) is a NAD+-dependent major mitochondrial deacetylase. In this study, we aimed to investigate SIRT3 levels and their target enzyme activities, including glutamate dehydrogenase (GDH), succinate dehydrogenase (SDH), and manganese superoxide dismutase (MnSOD), also to determine the antioxidant capacity and oxidative stress in tissue, mitochondria and serum samples in ovarian endometrioma patients. METHODS: We collected serum and endometrioma tissue samples from 30 patients. In the control group, we collected serum and eutopic endometrial tissue samples from 26 women without endometriosis. RESULTS: SIRT3 levels were significantly decreased in endometrioma tissue samples compared to the control group. There was no statistically significant difference in SIRT3 levels between patient and control serum samples. Furthermore, there was a decrease in GDH and SDH enzyme activities in both endometrioma tissue homogenate and mitochondria. MnSOD activity was decreased in tissue homogenate but increased in mitochondria and there was no difference in serum. While total SOD activity was decreased, CuZnSOD activity was increased in both tissue and serum samples. Besides these, total antioxidant capacity and advanced oxidation protein products (AOPP) levels were decreased in endometrioma tissue and mitochondria, but there was no difference in serum. CONCLUSIONS: Our results suggested that decreased levels of SIRT3 in endometrioma may be an important factor in the weakening of mitochondrial energy metabolism and antioxidant defense in endometriosis. We think that SIRT3 deficiency may be an important factor underlying the pathogenesis of endometriosis. More detailed studies are needed to reveal the relationship between SIRT3 and metabolism and oxidative stress in ovarian endometrioma.

The role of unfolded protein response in the pathogenesis of endometriosis: contribution of peritoneal fluid.

RESEARCH QUESTION: Endoplasmic reticulum stress (ERS) is caused by the accumulation of the misfolded or unfolded proteins in the endoplasmic reticulum and induces the unfolded protein response (UPR). Peritoneal fluid is important in the pathogenesis of endometriosis. In this study, the role of UPR associated with ERS in endometriosis, and peritoneal fluid, were investigated. DESIGN: Normal, eutopic and ectopic endometrium tissues were divided into menstrual cycle phases, and endometrial stromal cells (ESC) were treated with 10-20% concentration of control peritoneal fluid and peritoneal fluid obtained from women with endometriosis for 10, 30 and 60 min, and 24 and 48 h. The UPR signalling proteins were analysed immunohistochemically and immunocytochemically. Data were compared statistically. RESULTS: p-IRE1 was increased in ectopic glandular and stromal cells in the early proliferative phase compared with normal and eutopic endometrium. p-PERK increased in ectopic glandular and stromal cells in the late proliferative phase compared with normal endometrium. ATF6 was increased in ectopic glandular epithelium compared with normal endometrium in the proliferative phases, versus eutopic endometrium in the late secretory phase. p-IRE1 and p-PERK were increased in high concentrations of ESC treated with peritoneal fluid obtained from women with endometriosis for 10, 30 and 60 min compared with controls. In ESC treated with peritoneal fluid from women with endometriosis, p-IRE1 decreased at 24-48 h compared with 30 min. CONCLUSIONS: In endometriosis, UPR pathways are activated as highly dependent on cell type and phase. Also, p-PERK and p-IRE1 increased because of exposure to high-dose peritoneal fluid from women with endometriosis in stromal cells. Our findings provide a basis for further studies searching for a potential biomarker for the diagnosis of endometriosis.

Serum caveolin-1 levels in patients with preeclampsia.

Aim: The expressions of caveolin-1 have only been examined in the placental tissue of patients with preeclampsia and were reported to be low. Therefore, we decided to investigate the maternal serum levels of caveolin-1 in patients with preeclampsia.Material and methods: This cross-sectional study was conducted including 87 pregnant women; 32 with normal pregnancy and 55 with preeclampsia. Maternal serum levels of caveolin-1 were measured by using enzyme-linked immunosorbent assay kit (ELISA).Results: The mean serum caveolin-1 level was significantly lower in women with preeclampsia (PE) compared with the control group (11.48 ± 0.92 versus 12.94 ± 1.36 ng/ml) and being lowest in the early onset PE group (11.24 ± 0.74 ng/ml). Serum caveolin-1 concentrations did not correlate with maternal age and BMI. However, caveolin-1 concentrations were negatively correlated with systolic blood pressure (r = -0.467, p = .001) and diastolic blood pressure (r = -0.441, p = .001) as well as with umbilical artery resistance index (r = -0.275, p = .01).Conclusion: Maternal serum caveolin-1 levels are significantly lower in patients with PE than controls. The serum caveolin-1 levels inversely correlate with blood pressure and umbilical artery Doppler parameters.

Serum collectrin levels in patients with early- and late-onset preeclampsia.

AIM: The aim of this study is to investigate the maternal levels of collectrin in early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). To assess the correlation between serum collectrin levels and blood pressure in humans. MATERIAL AND METHODS: This cross-sectional study was conducted including 79 pregnant women, 27 with normal pregnancy, 30 with EOPE and 22 with LOPE. Maternal serum levels of collectrin were measured by using enzyme-linked immunosorbent assay kits. RESULTS: The mean serum collectrin level was significantly lower in women with PE compared with the control group (8.49 ± 3.12 ng/ml (EOPE), 9.69 ± 3.01 ng/ml (LOPE) versus 11.51 ± 4.33 ng/ml) and was found to be the lowest in the EOPE group (8.49 ± 3.12 ng/ml). The mean serum urea and uric acid levels were significantly higher in the PE group than the control group. Serum collectrin concentrations did not correlate with maternal age, BMI and serum creatinine levels. However, collectrin concentrations were negatively correlated with systolic blood pressure (r = -0.284, p = .011) and diastolic blood pressure (r = -0.275, p = .014) as well as with maternal serum urea (r = -0.269, p = .017) and uric acid (r = -0.219, p = .049) concentrations. CONCLUSION: Maternal serum collectrin levels are significantly lower in patients with preeclampsia than in the control group. There is an inverse correlation between serum collectrin levels and blood pressure.

Maternal serum autotaxin levels in early- and late-onset preeclampsia.

PURPOSE: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital. METHODS: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients. The control group was composed of 32 healthy pregnant patients. RESULTS: The mean autotaxin levels were 1.16 ± 0.97 and 0.7 ± 0.35 ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin levels were significantly higher in early-onset preeclampsia group compared with late-onset preeclampsia group. Autotaxin levels were found to be significantly higher in preeclamptic patients compared with control group. Serum autotaxin levels showed a significant positive correlation with maternal systolic, diastolic blood pressures and uric acid levels. CONCLUSION: Autotaxin might be a promising marker for detecting early-onset preeclampsia. However, further studies are necessary to confirm this hypothesis.

Does telomerase activity have an effect on infertility in patients with endometriosis?

OBJECTIVE: This study aimed to investigate the role of telomerase activity in the development of endometriosis-related infertility by evaluation of the serum telomerase in eutopic and ectopic endometrial tissue. STUDY DESIGN: Eutopic endometrium, cystic wall/ovarian cortex, and venous blood were assessed in forty-seven patients. The following groups of patients were identified: females with endometriosis requiring surgical intervention and healthy control females. Patients with histopathologically confirmed endometriosis were further subdivided in the infertile (n=14) and fertile (n=17) groups. Patients who underwent hysterectomy and oophorectomy for benign gynecological conditions were enrolled in the healthy control group (n=16). Telomerase activity was evaluated with three-group, endometriosis-based and fertility-based designs. Analyses were performed regardless the menstrual cycle phase (Phase G), in proliferative (Phase P) (n=22) and secretory phases (Phase S) (n=25). Telomeric Repeat Amplification Protocol PCR was applied for telomerase activity assessment. All statistical analyses were performed with STATA 14.2, GraphPad Prisma 7.01. RESULTS: In analyses of the eutopic endometrium, with three-group design, a significant difference was not found in Phase G and P (p=0.58 and p=0.33, respectively). However, a statistical difference was shown in Phase S (p=0.008). A significant difference was not established in Phase G, P and S of endometriosis-based design (p=0.35, p=1.0, p=0.13, respectively). No difference was detected in Phase G and P of fertility-based design (p=0.66 and p=0.14, respectively), whereas in secretory phase difference was approved (p=0,049). Telomerase activity was not established in ectopic endometrium and in serum assessment. CONCLUSIONS: Telomerase activity is useless as a biomarker in peripheric blood analysis. The absence of activity in cystic wall approves the high differentiation of endometriosis tissue, what is the possible reason of low malignancy risk. The high rate of telomerase activity in the eutopic endometrium of the infertile group may be considered as a cause of endometriosis-related infertility.

Progestin therapy in endometriosis.

Progestins are synthetic compounds that mimic the effects of progesteron. For over 50 years, oral progestins have been demonstrated to be effective in the treatment of endometriosis. They were reported to reduce or eliminate pain symptoms in approximately 90% of the patients. Progestins are available in many forms, including oral preparations, injections, subdermal implants and intrauterine systems. Continuous progestin use is an effective therapy for the treatment of painful symptoms associated with endometriosis but there had been no evidence of progestin use being superior to other types of treatment in endometriosis-related pain symptoms.

Promoting Effects of Heparin on ex vivo Expansion of Megakaryocytopoiesis from Human Cord Blood CD34+ Cells.

INTRODUCTION: Transfusion of ex vivo expanded megakaryocytes (MKs) has been proposed to sustain platelet recovery after cord blood (CB) hematopoietic stem cell transplantation. In this study, we investigated the effects of heparin on ex vivo colony forming unit-megakaryocytes (CFU-MKs) and MKs expansion from CB CD34+ cells. METHODS: CB CD34+ cells were stimulated by a combination of thrombopoietin (TPO), stem cell factor (SCF), Flt3-Ligand (FL), IL-6, and IL-11 supplemented with autologous serum and heparin during 14 days. Expanded cells were analyzed by flow cytometry and cultured in a CFU-MK assay. RESULTS: Compared to control cultures, the 5-factor combination with heparin induced significantly (p ≤ 0.05) higher numbers of: CFU-MKs and CD41+ cells on days 7 and 14; CD41+ cells displaying hyperploidy levels (≥8N) on day 14; platelets on day 14. The culture-derived platelets were activated upon collagen stimulation. CONCLUSION: Heparin can significantly enhance the stimulating effects of a combination of TPO, SCF, FL, IL-6, and IL-11 supplemented with autologous serum on CFU-MK, MK, and platelet production from CB CD34+ cells. This expansion system could represent a promising method to generate CFU-MKs and MKs cells for transfusion to sustain platelet reconstitution following CB transplantation.

Female genital system tuberculosis: a retrospective clinicopathological study of 1,548 cases in Turkish women.

PURPOSE: The incidence of tuberculosis (TB) has increased worldwide in the past decade and it still remains an important global public health problem. METHOD: A retrospective clinicopathological study of 1,548 cases of female genital tuberculosis between 1940 and 2011 was conducted. RESULTS: The mean age of the cases was 29.49 years. Involvement of the endometrium was noted in 1,073, fallopian tubes in 164, cervix in 157, and 154 had multiple organ involvement. Clinically, 115 cases (7.4%) were diagnosed as having primary infertility and 12 cases (0.8%) as having secondary infertility. There was a coexistent carcinoma in 1.5% of the cases. Peritoneal tuberculosis in 21 cases and tuberculous lymphadenitis in 7 cases were seen as well. CONCLUSION: The clinicopathological criteria of female genital tuberculosis in the different organs are described, and special attention is paid to infertility associated with tuberculous lesion, and awareness of the fact that the disease is still with us is thus particularly important.

Perinatal mortality and morbidity in twin pregnancies: the relation between chorionicity and gestational age at birth.

AIM: To investigate perinatal mortality and morbidity rates of twin pregnancies and to determine the underlying factors responsible for the increase in these rates. METHODS: Records of 300 twin pregnancies which have been followed in our clinic between 1996 and 2005 were reviewed retrospectively. Perinatal mortality and morbidity rates, zygocity, chorionicity, gestational age at delivery, route of conception, birth weight, route of delivery, fetal gender and cesarean rates were investigated. RESULTS: A total of 16,549 deliveries have been reviewed and 2.9% (n = 484) of these were detected to be twin deliveries. Perinatal mortality, adjusted perinatal mortality, fetal loss, neonatal mortality and perinatal morbidity rates were 7.5, 6.9, 3, 5.8 and 15.4%, respectively. The principal causes of perinatal mortality were prematurity, fetal demise and congenital abnormalities. The main cause of morbidity was respiratory distress syndrome (RDS). In neonatal period 28% of newborns needed neonatal intensive care unit (NICU) and 12.1% received positive pressured ventilation (PPV). Perinatal mortality and morbidity rates were found to be independent from zygocity, instead they were closely linked with chorionicity. Perinatal mortality and morbidity were higher if maternal age was under 18 and over 35, and were not effected by intrauterine growth retardation (IUGR), discordance between twins or RDS prophylaxis. CONCLUSION: Twin pregnancies have higher perinatal mortality and morbidity rates and potential obstetrical complications compared to singleton pregnancies, therefore should be monitored more intensely, appropriate precautions should be taken against obstetrical complications, especially before 31-32 weeks of gestation, deliveries should be performed in referral centers with competent NICUs.

Involvement of prostaglandin F2α in preeclamptic human umbilical vein vasospasm: a role of prostaglandin F and thromboxane A2 receptors.

OBJECTIVE: Preeclampsia is characterized by hypertension and proteinuria developing after 20 weeks of gestation. Increased vasoconstriction can be one of the major underlying pathophysiological event in this syndrome. We examined the role of vasoconstrictor prostanoid, prostaglandin F2α (PGF2α) in preeclamptic and normotensive human umbilical veins. METHODS: Umbilical veins were set up in organ bath. The concentration-response curves of PGF2α (endogenous agonist of prostaglandin F receptor) and fluprostenol (prostaglandin F receptor selective agonist) were determined in normal and preeclamptic veins either in the absence or presence of BAY u3405 (thromboxane A2 receptor selective antagonist). PGF2α and its major metabolite concentrations were measured by enzyme immunoassay kit. The expression of vasoconstrictor prostanoid receptors was determined by western blot. RESULTS: The concentration-dependent contractions to PGF2α and fluprostenol were significantly increased in umbilical vein preparations derived from preeclamptic women compared with those of normotensives. Increased reactivity was related with enhanced sensitivity to these spasmogens in preeclamptic veins. BAY u3405 (10 µmol/l) did not modify the responsiveness to PGF2α in normal umbilical veins whereas moderately reduced the contractions in preeclamptic preparations. Serum concentrations of PGF2α and its major metabolite, 13,14-dihydro-15-keto-PGF2α, were comparable between preeclamptics and normotensives whereas the metabolite concentration was elevated in umbilical cord serum of preeclamptics. 13,14-dihydro-15-keto-PGF2α, release was also increased in umbilical vein preparations of preeclamptic women. An increased prostaglandin F receptor protein expression was determined whereas EP3 and thromboxane A2 protein expressions were unchanged in preeclamptic umbilical veins. CONCLUSION: Prostaglandin F and thromboxane A2 receptors activation by PGF2α could be involved in umbilical vasospasm observed in preeclampsia.

Chitotriosidase and YKL-40 in normal and pre-eclamptic pregnancies.

OBJECTIVE: To compare macrophage activation in normal and pre-eclamptic pregnancies by determining YKL-40 concentration and chitotriosidase activity in maternal and cord serum. METHODS: In this prospective case-control study samples of maternal peripheral blood and umbilical venous blood were collected from 28 pre-eclamptic and 24 normotensive pregnant women and their newborns. YKL-40 concentration and chitotriosidase activity were determined by enzyme-linked immunoassay and fluorometry, respectively. RESULTS: Chitotriosidase activity in maternal and cord serum and YKL-40 concentration in cord serum were significantly higher in pre-eclamptic pregnancies (P<0.001), but there was no significant difference in maternal serum levels of YKL-40 between the case and control groups (P>0.05). There was a significant positive correlation between diastolic blood pressure and (1) chitotriosidase activity in both maternal and cord serum and (2) cord serum concentration of YKL-40 (r=0.61, r=0.84, and r=0.58, respectively). CONCLUSION: This study may be the first to demonstrate maternal and fetal macrophage activation in pre-eclampsia.

Transobturator tape (TOT) procedure with fluoroscopic guidance: gaining confidence and valuable experience!

OBJECTIVES: To report a successful transobturator tape (TOT) procedure performed under fluoroscopic guidance without any complications. METHODS: The diagnosis of stress urinary incontinence (SUI) was confirmed with urodynamic tests in a 54-year-old woman. TOT procedure was performed under the guidance of fluoroscopy. RESULTS: SUI was treated successfully with TOT procedure. Fluoroscopic guidance not only decreased the length of the procedure but also avoided the possible complications. The operator gained confidence and valuable experience. CONCLUSIONS: TOT procedure can be successfully performed under fluoroscopic guidance avoiding the possible complications and enhancing the learning curve period. We recommend the usage of fluoroscopy especially for the inexperienced operators. The benefits overweigh the cost of fluoroscopy and the absorbed dose of radiation which is calculated to be lower than accepted limits.

Effect of different hormonal therapies on thyroid function in surgical menopause: short-term results.

OBJECTIVE: To determine the effects of different hormone replacement therapy (HRT) regimens on thyroid function in surgical menopause. STUDY DESIGN: In a randomized, controlled study, 59 euthyroid women with surgical menopause were randomized to an estrogen-only (n=20), tibolone (n=20) or calcium-only (n=19) group. On the 5th postoperative day and 4th and 12th weeks, serum E2, TSH, free T3 and free T4 levels were determined. RESULTS: Although the initial and week 4 serum E2, TSH, free T3 and free T4 levels were comparable, the week 12 serum E2 and TSH levels were different between the subjects on estrogen therapy and those receiving tibolone or calcium only (p=0.008 and 0.000, respectively). Serum E2 levels were higher and TSH levels lower in subjects receiving estrogen. Moreover, serum TSH levels correlated negatively with serum E2 levels in the 12th week of estrogen use (r=-0.354, p=0.006). TSH increased in the tibolone group as compared to the estrogen group but was still lower than in the calcium-only group; however, the differences were not statistically significant. CONCLUSION: Irrespective of different regimens, HRT does not have an important short-term effect on thyroid function in women with surgical menopause.

Hyperprolactinaemia does not always mean 'hyperprolactinaemia'!

The presence of macroprolactinaemia was investigated in the symptom-free hyperprolactinaemia cases to reveal its incidence. The serum prolactin (PRL) fractions in 21 female patients with hyperprolactinaemia without any clinical symptoms were analyzed with PEG (polyethylene glycol precipitation) procedure. In 14 of these 21 cases, hyperprolactinaemia was detected with a high fraction of macroprolactin. In cases with asymptomatic hyperprolactinaemia, it is more appropriate to employ the PEG precipitation test to detect the disorder. High levels of serum prolactin, do not essentially indicate the presence of a prolactinoma but may only indicate macroprolactinaemia.

Seventeen-year review of hysterectomy procedures in a university clinic in Istanbul (1985-2001).

OBJECTIVE: Our objective was to review the hysterectomies performed in our clinic for the last 17 years to reveal the facts in relation to the operation. MATERIALS AND METHODS: The records of the patients who had undergone hysterectomy in Istanbul University Cerrahpasa School of Medicine Department of Obstetrics and Gynecology between January 1985 and August 2001 were reviewed retrospectively. Students' t-test and one-way ANOVA test were utilized to compare the data of different hysterectomy groups. RESULTS: Between 1985 and 2001, there were 3,956 women who had undergone hysterectomy operation in the Department of Obstetrics and Gynecology of Cerrahpasa School of Medicine, Istanbul University. There were 3,274 (82.7%) total abdominal hysterectomies (TAH), 424 (10.7%) total vaginal hysterectomies (TVH), 28 (0.7%) subtotal hysterectomies and 230 (5.8%) radical hysterectomies. There were no significant differences in the distribution of hysterectomy type with respect to interval of years. The common indications for hysterectomy were myoma uteri (38.49%), followed by gynecological cancers (21.6%) and uterine prolapse (11.9%). The rate of concurrent procedures were 87.3% for TAH (2,856/3,274) and 95.8% for TVH (406/424). The rate of 'unjustified' hysterectomies (pathological diagnosis that is inappropriate to the indication of the operation) determined as 8.9% in all of the cases. The pathological examination of the specimen was normal in 170 cases (5.1%) of TAH. This rate was 42.1% (183/435) in TVH group. In the TAH group there was no complication in 86.5% of the cases while it was 89.3% in the TVH group. The most common complication was febrile morbidity in the whole group. During the study period, 5 deaths that can be attributed to the hysterectomy operation were observed. The mortality rate was calculated as 0.1% for hysterectomy operation in the study period. CONCLUSION: Although it is widely performed, hysterectomy is a relatively safe surgical procedure. The morbidity and mortality of the operation may be further decreased by the efforts to minimize the rate of the unnecessary hysterectomies and selecting the most appropriate mode for the surgery.

Laparoscopic management of cornual pregnancy without sutures.

INTRODUCTION: Cornual pregnancy is a rare form of ectopic pregnancy. The incidence is reported as 3% of all ectopic pregnancies accounting 20% of deaths due to ectopic pregnancy. When an unruptured cornual pregnancy is diagnosed, there are a variety of management options. Many successful endoscopic management options for cornual pregnancy have been reported. CASE REPORT: In this case, cornual resection was performed. DISCUSSION: The other possible treatment options were reviewed.

Oxytocin infusion in labor: the effect different indications and the use of different diluents on neonatal bilirubin levels.

OBJECTIVE: To investigate the relationship of neonatal bilirubin levels to oxytocin infusion and the diluent used for oxytocin infusion. MATERIALS AND METHODS: The study was carried out as a prospective, randomized study in Istanbul University Cerrahpasa School of Medicine, Department of Obstetrics and Gynecology between January to December in 1995. A total of 80 patients managed with oxytocin during labor, enrolled to the study. These patients randomly divided into isotonic % 0.9 saline (Group 1) and 5% glucose solutions (Group 2) by a consecutive order using a balanced block randomization scheme. Forty multiparous patients delivering without oxytocin infusion formed the control group (Group 3). The details of maternal age, gestational age, labor duration, mode of delivery, birth weight of the babies, total volume of fluid administered until delivery and total oxytocin dose were noted in each case. Sodium and initial bilirubin levels were measured in the cord blood. Later on, capillary blood bilirubin and hematocrit concentrations were measured on day 1 and 2 in the newborn nursery. The groups were compared according to these parameters. RESULTS: The data of 29 patients in Group 1, 36 patients in Group 2 and 40 patients in Group 3 were suitable for analysis. The difference between study and control groups regarding the rate of hyponatremia, neonatal hyperbilirubinemia and neonatal jaundice was not statistically significant. Cord plasma sodium levels, cord plasma bilirubin levels and day 1 and 2 hematocrit and plasma bilirubin levels were not statistically different between the groups. irrespective of the diluent used, the cord plasma bilirubin levels and day 2 plasma bilirubin levels were significantly higher in the accelerated group. CONCLUSION: No significant effect of oxytocin infusion was revealed on neonatal hyperbilirubinemia unless oxytocin was for the augmentation of labor.