Özlem Bozoklu Akkar

The Efficacy of Bevacizumab, Sorafenib, and Retinoic Acid on Rat Endometriosis Model

Blood vessels are necessary for development and maintenance of the endometriosis and blood flow supplies oxygen and essential nutrient to the disease. Local angiogenesis is regulated by vascular endothelial growth factor (VEGF) and inhibitors of VEGF may be a novel therapeutic approach. We inducted endometriosis in 43 rats and they were randomly allocated into 4 groups. The rats in group I (control n = 11) were given no medication. The rats in group II (n = 11) were given bevacizumab. The rats in group III (n = 11) were given Sorafenib, and the rats in group IV (n = 10) were given retinoic acid (RA). Then groups were compared for microvessel density, VEGF, soluble tyrosine-kinase receptor, ovarian reserve, and treatment effectivity. All these medications were effective on endometriosis and we detected that volume of endometriotic implants were significantly decreased. Ovarian reserve was not affected from the medication, in addition RA have induced reproductive capacity.

Effects of Pazopanib, Sunitinib, and Sorafenib, Anti-VEGF Agents, on the Growth of Experimental Endometriosis in Rats.

We aimed to compare the effects of pazopanib, sunitinib, and sorafenib on endometriotic tissue morphology and histological characteristics as well as ovarian reserve in a rat model. Experimental endometriosis was established in 32 rats. They were randomly divided into 4 groups (8 rats for each group) to administer study drugs: pazopanib, sunitinib, sorafenib, and normal saline. Histological examination with hematoxylin and eosin staining to determine endometriosis score and immunostaining with primary vascular endothelial growth factor (VEGF), CD117, and Bax antibodies were performed. Bilateral ovaries excised to determine the ovarian follicle number. The endometriosis score was significantly reduced by pazopanib compared to other study drugs and by sunitinib compared to sorafenib and normal saline (P < .05). Sorafenib did not affect endometriosis score (P > .05). The VEGF score was significantly decreased similarly by pazopanib, sunitinib, and sorafenib compared to normal saline (P < .05). The CD117 score was reduced by pazopanib and sunitinib similarly compared to both sorafenib and normal saline that provided similar effect on the score (P < .05). The Bax scores of all the groups were found similar (P > .05). No study drugs caused meaningful change in the ovarian follicle number (P > .05). Pazopanib reduces the growth of endometriotic implants. This effect may be related to the suppressive effect of pazopanib on the endometriotic tissue expressions of VEGF and CD117 but not Bax. The study drugs do not affect ovarian reserve. The inconsistent effects of study drugs regarding study parameters require further studies to elucidate the molecular bases of their effects on the growth of endometriotic implants.

Effect of imatinib on growth of experimental endometriosis in rats

OBJECTIVE Currently, medical and surgical treatment options for endometriosis are limited due to suboptimal efficacy, and also safety and tolerance issues. Long-term use of gonadotrophin-releasing hormone analogs, androgenes, and the danazol, which are widely used drugs for endometriosis, is usually not possible due to their suboptimal safety and tolerance profile. The lack of an effective, tolerable and safe treatment option for endometriosis makes animal models of experimental endometriosis necessary to study candidate drugs. The aim of this study was to investigate the efficacy of imatinib on the experimental endometriosis in a rat model. STUDY DESIGN Endometriosis was induced by autotransplantation of uterine tissue into the peritoneal cavity. Twenty-four rats, which had visually confirmed endometriotic implants on subsequent laparotomy, were randomized into three groups to receive imatinib (25mg/kg/day, p.o.), anastrozole (0.004 mg/day, p.o.), or normal saline (0.1 mL, i.p.) for 14 days. After removal of endometriotic tissue and H & E staining, endometriosis score was determined according to a semiquantitative histological classification. Also, immunostaining with primary antibodies including VEGF, CD117, and Bax were used for immunohistochemical (IHC) examination. RESULTS Both anastrozole and imatinib suppressed the growth of endometriotic tissue and reduced the number of ovarian follicles. Although the difference was not statistically significant, imatinib was less effective than anastrozole for treatment of endometriosis. CONCLUSION Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation.

Value of in situ ovarian volume measured during cesarean delivery to assess the potential of diminished ovarian reserve

Abstract Objective: We aimed to determine the value of mean ovarian volume (OV) determined by three-dimensional in situ measurement of ovaries during cesarean delivery (CD) to assess the potential of diminished ovarian reserve (DOR) evaluated by hormonal and ultrasonographic parameters 3 months after the cesarean delivery. Methods: Each ovary was measured underwent CD in three dimensions, and three months after CD, the mean OV, serum AMH, FSH, LH, and estradiol levels, and antral follicle count (AFC) values were recorded as well as other demographic and obstetric parameters. Results: After categorizing the study subjects as having a potential of DOR by the criteria of serum AMH <1 pg/mL and AFC value ≤6, in patients with a potential of DOR, the mean intra-operative and post-operative OVs were significantly decreased (p < 0.05). Considering the correlation coefficients obtained by the correlations of post-operative AMH level and AFC value with the mean intra-operative and post-operative OV values, the mean intra-operative OV provided significantly higher correlation coefficients (p < 0.05). Conclusions: These findings, overall, support the diagnostic value of mean OV determined by the in situ measurement of three dimensions of left and right ovaries during cesarean delivery for the screening of potential for the DOR.

SDF-1/CXCL12 and CXCR4 gene variants, and elevated serum SDF-1 levels are associated with preeclampsia

ABSTRACT Objective: We aimed to compare the frequencies of stromal cell-derived factor-1 (SDF-1) 3′A and CXCR4 single-nucleotide polymorphisms (SNPs) and serum SDF-1 levels in patients with preeclampsia (PE). Methods: In total, 89 women with PE and 89 control women were included in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. Enzyme-linked immunosorbent assay method was used to measure serum SDF-1 level. Results: For SDF-1 3′A SNP, the frequency of GA genotype, total number of GA and AA genotypes, and the A allele frequency was higher in PE patients than controls (p = 0.04, 0.023, and 0.029, respectively). For CXCR4 SNP, the frequency of CT genotype, total number of CT and TT genotypes, and the T allele frequency were higher in PE patients than controls (p = 0.04, 0.006, and 0.005, respectively). SDF-1 serum level was detected higher in preeclamptic women compared with controls (p = 0.001). In PE patients, there was no significant association between serum SDF-1 levels and genotypes of SDF-1 3′A SNP. SDF-1 level was significantly higher in patients bearing CXCR4 CT genotype than CC genotype (p = 0.001). Furthermore, SDF-1 levels in patients bearing CT+TT genotype were found higher than that of patients with CC genotypes (p = 0.001). Conclusion: Results of our study suggest that SDF-1 3′A and CXCR4 polymorphisms and elevated serum SDF-1 levels may have a role in the development of PE.

Favorable Outcomes for both Mother and Baby Are Possible in Pregnant Women with Crimean-Congo Hemorrhagic Fever Disease: A Case Series and Literature Review

To assess the impact of Crimean-Congo hemorrhagic fever (CCHF) infection during pregnancy on maternal and fetal outcomes, we present the clinical and laboratory findings and outcomes of 5 pregnant women with CCHF infection as well as fetal outcomes. We also reviewed previously reported cases with CCHF infection in pregnant women. All pregnant women with CCHF infection who had been hospitalized between August 2007 and September 2011 were included. The gestational ages at the time of CCHF infection were 8, 18, 20, 21 and 32 weeks. CCHF infection was acquired during the 1st trimester in only 1 case and resulted in spontaneous abortion. The other 4 pregnant women completely recovered, all reached a healthy full-term gestation and 4 term babies were born. All infants had normal birth weight and were found to be healthy on their first examination and follow-up. In the literature concerning CCHF infection in pregnancy, 8 published articles including case reports or case series and 1 poster presentation including 1 case could be accessed. In conclusion, there is a risk of vertical transmission of CCHF infection, and infections acquired early in gestation had a poor prognosis for the fetus.

Evaluation of ovarian reserve using anti‐müllerian hormone and antral follicle count in Sjögren's syndrome: Preliminary study

The aim of this study was to determine ovarian reserve status using anti‐müllerian hormone (AMH) level and antral follicle count (AFC) in patients with Sjögrens syndrome (SS).

Genetic variants in the microRNA machinery gene (Dicer) have a prognostic value in the management of endometrial cancer

Aim: Although several associations were found between Dicer rs3742330 single nucleotide polymorphism (SNP) and development and prognosis of some epithelial cancers, relationship between the SNP rs3742330 and endometrial cancer (EC) has not yet been studied. We aimed to investigate the prognostic role of rs3742330 SNP of Dicer gene in EC patients. Subjects and Methods: A total of 80 EC patients and 80 control subjects included in the study. Real-time polymerase chain reaction and the allele discrimination technique was used for genotyping of rs3742330 SNP. Results: There was no significant difference between EC patients and control subjects with regard to the genotype and allele frequencies for Dicer rs3742330 SNP (P > 0.05). Despite Dicer rs3742330 SNP had no prognostic value in terms of stage, grade, lymphovascular invasion, myometrial invasion, tumor size, and histopathology; malignant peritoneal cytology has been detected higher in the patients bearing AA genotype compare with AG genotype (P = 0.023). Higher recurrence rate and shorter time to recurrence were found in patients bearing AG and GG genotype compare with AA genotype (P = 0.009). Conclusion: Dicer rs3742330 AG and GG genotypes may have the potential to be used as a predictor of poor prognosis in the management of EC case.

Primary Sjögren’s Syndrome Adversely Affects the Female Sexual Function Assessed by the Female Sexual Function Index: A Case-Control Study

Objectives This study aims to evaluate the sexual function of females with primary Sjögrens syndrome (pSS) in comparison to healthy females by using the Female Sexual Function Index (FSFI). Patients and methods This case-control study included 31 female patients (mean age 46.0±10.2 years; range 30 to 68 years) with pSS and 27 healthy females (mean age 44.2±8.5 years; range 30 to 55 years) as control group. The sexual function of the participants was assessed by 19-item FSFI. Results Mean duration of pSS in the patient group was 35.9 months (range 3 to 264 months). Significantly higher number of pSS patients reported positive history for vaginal infection compared to controls (n=26, 83.9% vs. n=7, 25.9%, respectively; p<0.001) without any difference in endocervical culture result. Cervical smear assessment revealed more inflammation and atrophy in patient group compared to control group (p=0.001). Mean FSFI total score was significantly lower in patient group than control group (18.9±9.9 vs. 25.1±5.1, respectively; p=0.004). Similarly, five out of six domains of FSFI -arousal, lubrication, orgasm, satisfaction, and pain- were significantly lower in patient group. FSFI total and subscale scores, except for pain, were found to be negatively correlated with duration of pSS. Conclusion The pSS causes sexual dysfunction in female patients. Furthermore, as disease duration increases, female sexual function decreases. Clinical management of female patients with pSS should cover the assessment of their sexual functionality and taking the necessary precautions to maintain satisfactory quality of life and treatment outcome.

Evaluation of Maternal Serum 25-Hydroxyvitamin D, Paraoxonase 1 Levels, and Neutrophil-to-Lymphocyte Ratio in Spontaneous Preterm Birth

Background The aim of this study was to evaluate the association of maternal serum 25-hydroxyvitamin D, paraoxonase 1, and neutrophil-to-lymphocyte ratio in women having early spontaneous preterm birth without clinical chorioamnionitis. Material/Methods This study was prospectively administered in women referred to our obstetrics service with preterm labor that resulted in preterm birth (n=35) and term labor that ended in term birth (n=44). The maternal serum levels of 25-hydroxyvitamin D and paraoxonase 1 were measured and neutrophil-to-lymphocyte ratio was calculated. Results The 25-hydroxyvitamin D and paraoxonase 1 levels of the preterm group were significantly lower than those of the term group (p<0.05). The neutrophil-to-lymphocyte ratio value of the preterm group was significantly higher than that of the term group (p<0.05). There was a significant but small positive correlation between the serum levels of 25-hydroxyvitamin D and paraoxonase 1 in the preterm group (r=0.35; p=0.021). Conclusions Decreased maternal serum 25-hydroxyvitamin D and paraoxonase 1 levels and increased neutrophil-to-lymphocyte ratio may have a role in the etiology of spontaneous preterm birth.