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.

Comparison of Effectiveness of Laminaria versus Vaginal Misoprostol for Cervical Preparation Before Operative Hysteroscopy in Women of Reproductive Age: A Prospective Randomized Trial.

STUDY OBJECTIVE: To compare the effectiveness and safety of intracervical laminaria dilator versus intravaginal misoprostol administered before surgery to facilitate cervical dilation before operative hysteroscopy. DESIGN: A prospective randomized study (Canadian Task Force classification 1). SETTING: A university hospital. PATIENTS: A total of 150 women were assigned at random to the following groups: laminaria dilation (n = 50), misoprostol dilation (n = 50), and mechanical dilation (n = 50). INTERVENTIONS: Hysteroscopic surgery of intrauterine lesions. MEASUREMENTS AND MAIN RESULTS: In this study, 150 women were assigned at random to receive cervical priming with an intracervical laminaria dilator, 200 µg of intravaginal misoprostol, or a mechanical dilator before operative hysteroscopy. Cervical response, surgical outcome, and complications of operative hysteroscopy were assessed. Visual analog scale (VAS) pain scores were recorded in the misoprostol and laminaria dilation groups. Demographic variables of the study groups were comparable (p = .278-.988). The duration of cervical pretreatment was similar with the intracervical laminaria dilator and intravaginal misoprostol (p = .803); however, intravaginal misoprostol was associated with more adverse effects (p = .031). Compared with the misoprostol dilation group, in which all patients required additional cervical dilation, notably fewer patients in the laminaria dilation group required additional cervical dilation after cervical preparation (p = .001). VAS pain scores were significantly higher in the laminaria dilation group, however (p = .001). CONCLUSION: Cervical priming with an intracervical laminaria dilator before operative hysteroscopy reduces the need for cervical dilation and better facilitates hysteroscopic surgery compared with intravaginal misoprostol. Oral analgesic use may be required before the use of this device.

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.

Hypogastric artery ligation for obstetrical hemorrhage: clinical experience in a tertiary care center.

BACKGROUND/AIM: Several authorities advocate the use of hypogastric artery ligation (HAL) in the treatment of cases of obstetrical hemorrhage related to uterine atony or placenta accreta. We assessed the morbidity and mortality of patients who underwent HAL as a component of emergency procedures to control life-threatening uterine bleeding in a tertiary-care university hospital. MATERIALS AND METHODS: In this retrospective study, the clinical data of 24 eligible patients who underwent HAL between 2010 and 2013 in a university hospital to prevent or control severe uterine bleeding were collected and analyzed with regard to intraoperative and postoperative findings. RESULTS: In the study population, there were nine patients with uterine atony managed without hysterectomy after HAL and there were 15 patients with placenta previa complicated with placenta accreta after HAL. Of these 15 patients, seven underwent hysterectomy and eight were managed without hysterectomy. Overall, the clinical features of the patients managed with or without hysterectomy were similar for patients with uterine atony and placenta previa. CONCLUSION: We suggest that if HAL is performed in a surgical setting as mentioned in this study, it may be a life-saving and fertility-sparing procedure.

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.

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.