Ertan Adali

Circulating levels of obestatin and copeptin in obese and nonobese women with polycystic ovary syndrome

OBJECTIVE Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies, affecting 5-8% of reproductive-age women. It is associated with insulin resistance, central obesity, type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases. The current study was undertaken to evaluate serum copeptin and obestatin levels, carotid artery intima-media thickness, and brachial artery flow mediated dilatation in obese and nonobese women with PCOS and age-matched healthy controls and to investigate their relationship with each other and with clinical, metabolic, and hormonal parameters and cardiovascular risk factors. METHOD In the study population, we analyzed 60 patients with PCOS and 30 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (BMI>30kg/m(2), n=30) or nonobese group (BMI<30kg/m(2), n=30). History was obtained and a physical examination, peripheral venous blood sampling, and carotid and brachial artery ultrasonography were performed. Serum copeptin and obestatin levels, total testosterone, C-reactive protein (CRP), glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, homeostasis model assessment for insulin resistance (HOMA-IR), carotid artery intima-media thickness (CIMT), and brachial artery flow-mediated vasodilation (FMD) were determined and compared among the groups. RESULTS Women with PCOS, especially obese ones, had higher triglycerides, HOMA-IR, total testosterone, CRP, systolic and diastolic blood pressure, and waist-to-hip ratio (WHR), and lower HDL. Serum obestatin levels were significantly lower in the obese PCOS group than they were in the nonobese and control groups (p<0.001). Serum copeptin levels were significantly higher in the obese PCOS group than they were in the nonobese PCOS and control groups (p<0.001). CIMT values were similar among the groups (p>0.05). Brachial artery FMD was lower in the PCOS groups than it was in the control group (p<0.001). Obestatin and FMD values were negatively correlated with cardiovascular risk factors, whereas copeptin was positively correlated. A significant positive correlation was found between copeptin, BMI, WHR, hirsutism score, total testosterone, and HOMA-IR. There was no correlation between CIMT, copeptin, obestatin, and FMD. A positive correlation was seen between CIMT, BMI, triglycerides, and HOMA-IR. CONCLUSION Copeptin and obestatin may provide useful information regarding future cardiovascular risk in PCOS patients as copeptin was positively correlated and obestatin was negatively correlated with cardiovascular risk factors.

Effect of 2-aminoethoxydiphenyl borate on ischemia-reperfusion injury in a rat ovary model

OBJECTIVE The aim of this study is to evaluate the effects of 2-aminoethoxydiphenyl borate (2-APB) as an antioxidant and analyze biochemical and histopathologic changes in experimental ischemia-reperfusion (I/R) injury in rat ovaries. STUDY DESIGN Thirty female rats were utilized to create four groups. Group 1: I/R and 2-APB (2mg/kg); Group 2: I/R and 2-APB (4mg/kg); Group 3: I/R; Group 4: sham operation. Ovarian tissue and serum malondialdehyde, nitric oxide (NO) levels; ovarian tissue and serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) were determined. In ovarian tissue samples histopathologic examination, immunoflourescence staining by TUNEL method was studied. RESULTS Tissue TOS, serum TOS, and OSI levels were elevated in I/R group. After treatment with 2-APB, tissue and serum TOS levels and OSI levels were markedly decreased. There was a significant difference in terms of tissue and serum NO levels between the sham group and I/R group. Elevation in tissue NO and serum NO levels were decreased after treatment with 2-APB. TUNEL-positive cell number gradually decreased with dose of 2-APB in groups 1 and 2. CONCLUSION Conservative treatment with 2-APB is beneficial for mitigation of I/R injury, and the ovarian protective effect of 2-APB appears to be mediated through its antiapopitotic and antioxidative effects.

Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats

Abstract The aim of this study is to evaluate the effects of sildenafil citrate on cisplatin-induced ovarian toxicity. Thirty-two female rats were divided into four groups. Group 1: saline control; group 2: cisplatin; group 3: sildenafil citrate; and group 4: cisplatin plus sildenafil citrate group. In groups 2 and 4, the rats were injected with 5 mg/kg cisplatin intraperitoneally (i.p.). In groups 3 and 4, the rats were injected with 1.4 mg/kg sildenafil citrate i.p. The ovaries were removed two weeks later in all groups. Histopathologic examination, follicle counting and classification were performed. The expression of anti-Müllerian hormone (AMH) was detected immunohistochemically in the ovarian tissues. Sildenafil alleviated cisplatin-induced histopathological changes in the ovarian tissue. Primordial, secondary and tertiary follicles were diminished in group 2 compared with group 1 (p < 0.05). Pretreatment with sildenafil citrate preserved primordial follicle count in group 4 compared with group 2, and the difference was statistically significant (p < 0.05). According to our results, immunoreactivity intensity of AMH was lower in group 2 compared with group 1 (92.4 ± 3.97 versus 88.8 ± 1.77) but not significantly, whereas immunoreactivity intensity of AMH was higher in group 4 compared with group 2 (88.8 ± 1.77 versus 94.1 ± 2.36; p < 0.05). Our results demonstrated that pretreatment with sildenafil citrate is beneficial for protecting the ovaries from cisplatin-induced damage. Sildenafil citrate can be a choice for fertility preservation.

A Humanized Anti-Interleukin 6 Receptor Monoclonal Antibody, Tocilizumab, for the Treatment of Endometriosis in a Rat Model

Objective: The aim of this study was to investigate the efficacy of anti-interleukin 6 (IL-6) therapy in the treatment of endometriosis in a rat model. Study Design: After the peritoneal implantation of autologous endometrial tissue, 22 Wistar female rats were divided to create 2 intervention groups: the tocilizumab group (n = 13) and the control group (n = 9). After measuring implant volume, saline was administered to the rats in the control group and 8 mg/kg tocilizumab was administered intraperitoneally to the rats in the tocilizumab-treated group every 2 weeks. After a 4-week treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate the preservation of epithelia. Fibrosis score was assessed between the groups. Ectopic and eutopic endometrium were evaluated immunohistochemically for IL-6 and vascular endothelial growth factor (VEGF). Results: There was a significant difference between the volumes of implants before and after treatment in the tocilizumab group (P < .05). The posttreatment volumes of lesions were smaller in the tocilizumab group than in the control group. Histologic and fibrosis scores were lower in the tocilizumab group than in the control group. Immunoreactivity intensity for VEGF was significantly decreased in the tocilizumab group for ectopic and eutopic endometrium (P < .05). Interleukin 6 levels and endometrial thickness for ectopic and eutopic endometrium were similar between the groups. Conclusion: Tocilizumab treatment had a regressive effect on the endometriotic implants.

Accessory spleen in the pelvis: A case report

Highlights • Ectopic splenic tissue can be either congenital (accessory spleen) or acquired (splenosis).• Accessory spleen (AS) is commonly located near the spleen’s hilum and in the pancreas tail.• Pelvic AS is a very rare entity.• AS is generally determined incidentally during radiological investigation or surgery.• Pelvic AS may be considered in differential diagnosis of adnexal masses.

The Expression of Cyclophilin A in Ovarian Endometrioma: Its Correlation with Recurrence and Vascularity

Endometriosis is defined as the presence of functional endometrial tissues outside of the uterine cavity. Ovarian endometrioma is the most common type of endometriosis. It is an estrogen-dependent inflammatory disease that frequently causes infertility and chronic pelvic pain. Cyclophilin A (CyPA) is secreted from various types of cells in response to inflammatory stimuli. Many previous studies have shown that the increased expression and/or heightened plasma levels of CyPA exacerbates inflammation. The aim of this study is to evaluate CyPA immunoreactivity in ovarian endometrioma cyst wall. In this cross-sectional study, CyPA immunoreactivity in endometrial tissue samples obtained from uterine cavity and in endometrioma cyst walls of 44 consecutive women with ovarian endometrioma were compared with control endometrial tissue samples obtained from uterine cavity of 40 women without endometrioma. All endometrioma samples were confirmed via histopathological examination. Finally, the relationship between CyPA immunoreactivity and the clinicopathological findings related to endometrioma were evaluated. The CyPA expression rates in glandular cells, stromal cells, and the capillary endothelium were significantly higher in endometrioma cyst walls of women with ovarian endometrioma than in the control endometrial tissue of women without endometrioma (p = 0.0002, p = 0.0417 and p = 0.0067, respectively). The correlation analysis demonstrated that glandular CyPA expression was correlated with endometrioma recurrence (p = 0.0267). However, stromal and vascular endothelial CyPA expression were correlated with dysmenorrhea recurrence (p = 0.0023 and p = 0.0003, respectively). In conclusion, the increased expression of CyPA in ectopic endometrial tissue is associated with endometrioma recurrences and vascularity.

Prevention of ovarian hyperstimulation syndrome in a rat model: comparison of the efficacy of tocilizumab with that of ranibizumab, cabergoline, and a gonadotropin-releasing hormone antagonist.

Abstract The aim of the study is to investigate the effects of the interleukin-6 (IL-6) blocker tocilizumab in a hyperstimulated rat model and compare it with ranibizumab, a gonadotropin-releasing hormone antagonist (GnRHA), and cabergoline. Forty-seven rats were randomly divided into the following seven groups: Group 1: OHS; Group 2: OHS+ GnRHA; Group 3: OHS + ranibizumab; Group 4: OHS + cabergoline; Group 5: OHS + low-dose tocilizumab (TL); Group 6: OHS + high-dose tocilizumab (TH); Group 7: sham. Ovarian weight was significantly lower only in the ranibizumab group than in the OHS group. Estrogen levels were significantly lower in the GnRHA group than in the OHS and the treatment groups. Progesterone levels were significantly lower in the ranibizumab, cabergoline, and TL groups than in the OHS group. Among the treatment groups, corpus luteum counts were lower than in the OHS group. Corpus luteum counts were lowest in the tocilizumab groups. IL-6 intensity was lower in all treatment groups than in the OHS group. In the ranibizumab group IL-6 intensity was the lowest. The TL group did not significantly differ from the GnRHA and cabergoline groups regarding IL-6 expression. Ovarian VEGF expression was significantly lower in all treatment groups. For the TL, ranibizumab, and cabergoline groups VEGF intensity was similar. Tocilizumab may be a new strategy for preventing ovarian hyperstimulation syndrome by inhibition of IL-6.

The Usefulness of CD34, PCNA Immunoreactivity, and Histopathological Findings for Prediction of Pain Persistence After the Removal of Endometrioma

Endometriosis is an estrogen-dependent inflammatory disease that causes infertility and chronic pelvic pain. Ovarian endometrioma is the most common form of endometriosis, and conservative surgery is the main preferred therapeutic approach for endometrioma-associated symptoms. The aim of this study was to investigate the persistence of cyclic and noncyclic pelvic pain (NCPP) after endometrioma excision and their relationship to clinical and histopathological findings. In this prospective observational study, 41 symptomatic patients were evaluated for the presence of pain symptoms 3 to 6 months after endometrioma excision. Tissue specimens of endometrioma were collected during the operation and embedded in paraffin. The persistence of pain was 41.4%. Surgical excision of endometrioma significantly decreased NCPP and dysmenorrhea, but not dyspareunia (P < .0001, P = .0001, and P = .25, respectively). Histopathological changes, including depth of endometriosis penetration into the cyst wall, the presence of macrophage infiltration, and vascularity of endometrioma cyst walls were significantly higher in patients with pain persistence than in patients without pain persistence (P = .0034, P = .0042, and P = .0007, respectively). Moreover, proliferating cell nuclear antigen (PCNA) and CD34 immunoreactivity in both glandular and stromal cells and vascular endothelium were significantly higher in patients with pain persistence (P = .0079 and P = .0025, respectively). Additionally, these histopathological changes and PCNA and CD34 immunoreactivity were significantly correlated with the persistence of NCPP and dysmenorrhea. The discovered differences in patients with endometrioma with or without pain persistence may indicate a possible relationship between endometrioma-associated pain and histopathological variability of endometrioma.

Placental fractalkine immunoreactivity in preeclampsia and its correlation with histopathological changes in the placenta and adverse pregnancy outcomes

Abstract Introduction: Preeclampsia is a systemic inflammatory disorder and a major cause of maternal and fetal mortality. Fractalkine (CX3CL1) is a member of the chemokine family with multiple functions in the organization of the immune system. It is up-regulated in inflammatory disorders. During inflammation, fractalkine enhances tissue destruction and inflammatory cell invasion. We aimed to investigate the alteration of fractalkine in the placental tissues of pregnant women with preeclampsia and the correlation of this alteration with clinicopathological variables. Materials and methods: Alteration of fractalkine in placental tissue specimens was determined immunohistochemically in 84 pregnant women: 33 women with mild preeclampsia, 19 women with severe preeclampsia, and 30 women with normal pregnancy. Preeclampsia was diagnosed using current guidelines of the American College of Obstetricians and Gynecologists. Results: Pregnant women with mild and severe preeclampsia revealed significantly higher fractalkine expression in syncytiotrophoblast cells than in the normotensive group (p = .0051 and .0001, respectively). The expression of fractalkine in preeclampsia was positively correlated with clinical parameters including the presence of intrauterine growth restriction, systolic and diastolic blood pressure, and 24-h urine protein, whereas it was negatively correlated with plasma albumin levels and placental weight. Additionally, the pathological changes in the placenta-including the presence of syncytiotrophoblast basement membrane thickening, increased number of syncytial knots, and vascularization of terminal villi were significantly correlated with fractalkine expression in pregnant women with preeclampsia. Conclusions: Overexpression of fractalkine in pregnant women with preeclampsia, as well as the correlation between fractalkine expression and poor pregnancy outcomes and placental histopathological changes may be associated with the underlying mechanisms of preeclampsia.

Osteogenesis imperfecta Type IV: a newly identified variant at position c.560 (G > T; p.Gly187Val) in the COL1A2 gene

Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis of the newborn revealed a novel mutation at position c.560 (c.560 G > T) of the exon 12 in the COL1A2 gene; which lead to the glycine modification with valine (p.Gly187Val) at codon 187. The pregnancy follow-up was uneventful. After delivery, the newborn underwent biphosponat therapy and no fracture was detected until 1 year old.