Halil Gursoy Pala

The effects of sunitinib on endometriosis

Abstract The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Students t-test, analysis of variance (ANOVA) and the Mann–Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.

Ovarian failure in diabetic rat model: Nuclear factor-kappaB, oxidative stress, and pentraxin-3

OBJECTIVE The aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models. MATERIALS AND METHODS An experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-κB immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Müllerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann-Whitney U and χ(2) tests. RESULTS We found statistically significantly lower glutathione and anti-Müllerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration, stromal fibrosis scores, and NF-κB immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups. CONCLUSION These findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-κB pathway with resveratrol. We thought that the NF-κB pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Müllerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further.

Prenatal Diagnosis of Congenital High Airway Obstruction Syndrome: Report of Two Cases and Brief Review of the Literature

Congenital high airway obstruction syndrome (CHAOS) is the obstruction of the fetal upper airways, which may be partial or complete. It is usually incompatible with life. Prenatal recognition of the disease is quite important due to the recently described management options. We report here two cases of CHAOS due to tracheal atresia diagnosed by antenatal ultrasonography and fetal MRI. We also briefly review the relevant literature with the associated management options.

Three-dimensional ultrasonographic placental volume in gestational diabetes mellitus

Abstract Objectives: We aimed to evaluate the placental volume and placental mean gray value in gestational diabetes mellitus (GDM) and healthy placentas using three-dimensional (3D) ultrasound and Virtual Organ Computer-aided AnaLysis (VOCAL). Methods: This case-control prospective study consisted of 39 singleton pregnancies complicated by GDM and 42 healthy singleton pregnancies matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. The placental volume (cm3) was analyzed using the VOCAL imaging analysis program and 3D histogram was used to calculate the volumetric mean gray value (%). Results: Placental volume was significantly larger in GDM (411.59 ± 170.82 versus 343.86 ± 128.94 cm3; p = 0.046). There was no significant difference in mean gray value between GDM and healthy placentas (36.65 ± 7.02 versus 38.71 ± 7.91, respectively; p = 0.277). Placental volume was significantly correlated with gestational week (r = 0.219, p = 0.035) and parity (r = 0.228, p = 0.048). There was negative significant relation between placental volume and umbilical artery systolic/diastolic ratio, pulsatility index and resistance index (r = −0.278, p = 0.007; r = −0.315, p = 0.002; r = −0.322, p = 0.001, respectively). Conclusions: Placental volume increases significantly in GDM, whereas mean gray values do not alter significantly. These data may reflect the placental changes in GDM placentas that may help to understand the pathophysiology better.

The alteration in placental volume and placental mean grey value in growth-restricted pregnancies assessed by 3D ultrasound: (Growth Restriction & 3D Ultrasonography)

Abstract We aimed to evaluate the volumetric and echogenic alterations in placentas between the intrauterine growth restriction (IUGR) and normal pregnancies using three-dimensional ultrasound and virtual organ computer-aided analysis (VOCAL) software. This case–control prospective study consisted of 48 singleton pregnancies complicated by IUGR and 60 healthy singleton pregnancies matched for maternal age, gestational age and parity. Placental volume (PV) and placental volumetric mean grey values (MGV) were evaluated. PV (cm3) was analysed using the VOCAL imaging analysis program, and 3D histogram was used to calculate the volumetric MGV (%). PV was 278.50 ± 63.68 and 370.98 ± 97.82 cm3 in IUGR and control groups, respectively (p = 0.004). MGV of the placenta was 38.24 ± 8.41 and 38.24 ± 8.41 in IUGR and control groups, respectively (p = 0.30). receiver operator curve (ROC) curve analysis revealed that area under curve was 0.731 for PV. Correlation analysis revealed that PV was significantly associated with estimated fetal weight (r = 0.319, p = 0.003), biparietal diameter (r = 0.346, p = 0.002), head circumference (r = 0.269, p = 0.019), abdominal circumference (r = 0.344, p = 0.002) and femur length (r = 0.328, p = 0.004). PV was inversely related to the umbilical artery pulsatility index (r = − 0.244, p = 0.017). To the best of our knowledge, this is the first study evaluating volumetric MGV in IUGR placentas by comparing them with healthy pregnancies. Our study showed that PV diminishes significantly in IUGR pregnancies, whereas volumetric MGV does not alter significantly.

The Protective Effect of Granulocyte Colony-Stimulating Factor on Endometrium and Ovary in a Rat Model of Diabetes Mellitus

Aims: To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on the endometrium and ovaries in an experimental diabetes mellitus (DM) rat model. Methods: A total of 18 female Sprague-Dawley albino mature rats (8 weeks, 200-220 g) were used in this study. Diabetes was induced by intraperitoneal (i.p.) injection of streptozocin randomly in 12 rats. No drug was administered to the remainder of the rats (control group, group 1, n = 6). The other 12 rats were randomly divided into 2 groups; 1 ml/kg i.p. saline was given as vehicle to group 2 (diabetic nontreated control group, n = 6) and 100 µg/kg/day of i.p. G-CSF was given to group 3 (G-CSF-treated group, n = 6) for 4 weeks. After 4 weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Results: The mean endometrial gland degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Ovarian follicle degeneration, stromal degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Plasma TGF-β and malondialdehyde levels were significantly lower in groups 1 and 3 compared with group 2. Antimüllerian hormone levels were significantly lower in group 2 compared with groups 1 and 3. Conclusion: Glucose toxicity occurred severely in the ovaries and endometrium of the DM rats. After G-CSF treatment, ovarian and endometrial injury and fibrosis scores decreased significantly. The effects of G-CSF in rat models give hope to improved treatment of human DM complications such as premature ovarian failure and endometrial dysfunction.

Abnormal Elevated CA 19-9 in the Dermoid Cyst: A Sign of the Ovarian Torsion?

Dermoid cyst is the most common germ cell tumor of the ovary containing various tissue elements. Ovarian torsion is a common complication of which ultrasonographic diagnosis is confusing. We report here a 14-year-old adolescent with painless torsion of the ovary including dermoid cyst and with abnormal elevated CA 19-9 serum levels. Elevated CA 19-9 level may be related to ovarian torsion and may predict the extent of tissue necrosis.

Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study.

Abstract The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) – Group-2 and sunitinib treatment group – Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student’s t-test, analysis of variance (ANOVA) and Mann–Whitney’s U-test. There was a significant increase in no-medication (water given) diabetic rat’s ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats’ ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat’s ovary (Group-3) when compared with no-medication (water given) diabetic rat’s ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.

The assessment of placental volume and mean gray value in preeclamptic placentas by using three-dimensional ultrasonography.

Abstract Objectives: We aimed to evaluate the placental volume and placental mean gray value in preeclampsia and healthy placentas by using three-dimensional (3D) ultrasonography and Virtual Organ Computer-aided AnaLysis (VOCAL). Methods: This case–control prospective study consisted of 27 singleton pregnancies complicated by preeclampsia and 54 healthy singleton pregnancies matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. The placental volume (cm3) was analyzed using the VOCAL imaging program, and 3D histogram was used to calculate the volumetric mean gray value (%). Results: Preeclamptic and control group consisted of 27 (mean age: 28.90 ± 5.95 years, mean gestation: 32.0 ± 4.55 weeks) and 54 (mean age: 29.48 ± 5.78 years, mean gestation: 32.61 ± 4.23 weeks) singleton pregnancies, respectively. Placental volume was significantly smaller in preeclampsia (250.62 ± 91.69 versus 370.98 ± 167.82 cm3; p = 0.001). Volumetric mean gray value of the placenta was significantly higher in preeclampsia (38.24 ± 8.41 versus 33.50 ± 8.90%; p = 0.043). Placental volume was significantly correlated with the estimated fetal weight (r = 0.319; p = 0.003). There was negative significant relation between placental volume and umbilical artery pulsatility index, resistance index and systolic/diastolic ratio (r = –0.244, p = 0.024; r = –0.283, p = 0.005; r = –0.241, p = 0.024, respectively). Conclusions: Placental volume diminishes significantly in preeclampsia, whereas volumetric mean gray values increases. This may reflect the early alterations in preeclamptic placentas, which may help to understand the pathophysiology better.

Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats.

Abstract We aimed to evaluate: (1) endometrial and ovarian tissue injury caused by the glucose toxicity in diabetic rat model and (2) the effect of GLP-1 analog (exenatide) on endometrial and ovarian diabetes induced injury with emphasizing the underlying mechanism. The study group composed of 24 female rats assigned randomly into 3 groups. Group 1 was the control group (n = 8) and received no treatment. Diabetes was induced by intraperitoneal injection of streptozocin for 16 rats which are further assigned randomly into 2 groups: 1 ml/kg intraperitoneal saline was given to Group-2 (diabetic non-treated control group, 8 rats) and 10 µg/kg/day of intraperitoneal exenatide was given to Group 3 (exenatide treated group, 8 rats) for four weeks. After four weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Diabetes caused endometrial and ovarian tissue injury in rats (p < 0.0001). Serum transforming growth factor beta (TGF-ß), malonylaldehyde (MDA), pentraxin-3 (PTX-3) levels were higher in diabetic rats (p < 0.0001), whereas antimullerian hormone (AMH) was lower (p < 0.001). Serum levels of these markers reflected that Diabetes induced injury in the reproductive tract occured via oxidative stress, fibrosis and severe inflammation. Diabetes diminished ovarian reserve. Exenatide treatment improved the histological degeneration and fibrosis in the endometrium and ovary with concomitant decrease in inflammatory and oxidative stress markers (p < 0.05). Exenatide also improved ovarian reserve (p < 0.05). Glucose toxicity occured severely in ovary and endometrium in DM. After exenatide treatment; ovarian and endometrial injury and fibrosis seems to decrease significantly. The effects of exenatide in rat models give hope to prevent the women with DM from premature ovarian failure and endometrial dysfunction.