Search

Objectives: The most diagnosed tumor among infiltrating tumors of the female genital tract is endometrial carcinoma. The Wnt/β-catenin signaling pathway has an important role in organogenesis, self-renewal of tissues, and adult stem cell maintenance. However aberrant activation of it causes many types of tumors and also related to the prognosis of patients. Therefore, we aimed to investigate whether Wnt/β-catenin pathway inhibitors have any effect on the proliferation and migration of tumor cells. Methods: As cancer cell line, HEC-1A endometrial adenocarcinoma was used. The Wnt/β-catenin pathway inhibitors effects on proliferation and migration were demonstrated by real-time cell analysis device and wound healing model respectively. Results: Wnt/β-catenin pathway inhibitors FH535 (25 μM at 36th hour, p < 0.05; 50μM at 48th hour p < 0.001) and niclosamide inhibited cell proliferation (10, 25 and 50μM at 60th hours; p < 0.01, p < 0.05 and p < 0.001, respectively) whereas ICRT14 and IWP-2 did not. However only niclosamide which is also an antihelmintic drug inhibited migration of the cells in all concentrations tested (10, 25 and 50μM, p < 0.05). Conclusions: The present study shows that the Wnt/β-catenin pathway has an substantial role in both proliferation and migration of endometrial adenocarcinoma. We suggest that the antihelmintic drug niclosamide could be further investigated for its potential therapeutic effect in endometrial adenocarcinoma.

The aim of this study was to investigate the expression of RhoA/Rho-kinase in the uterus and the effect of Rho-kinase inhibitors on uterine contractions of dehydroepiandrosterone (DHEA) induced polycystic ovary syndrome (PCOS) rats. Forty-four female Sprague-Dawley (21 days old) rats divided into three groups: The control group (n = 14, any procedure was not performed), vehicle group (n = 14, 0.2 ml of sesame oil, subcutaneous injection, 20 days) and PCOS group (n = 16, DHEA 6 mg/100 g in 0.2 ml of sesame oil, subcutaneous injection, 20 days). The myometrium thickness and uterine wet weight were assessed. The mRNA and protein expressions of Rho A, the effect of Rho-kinase inhibitors (fasudil and Y-27632) on KCI, carbachol, and PGF2 alpha induced contractions were evaluated in the uterus. In the PCOS group, the myometrium thickness and uterine wet weight significantly increased compared to the control group and vehicle group. The mRNA expression level and the immunoreactive score of Rho A, ROCK 1, ROCK 2 were similar in all groups. In the PCOS group, KCI, carbachol, and PGF2 alpha induced uterine contractions significantly increased compared to the control group and vehicle group. Fasudil and Y-27632 significantly inhibited KCI, carbachol, and PGF2 alpha induced uterine contractions in all groups. In conclusion, the expression of Rho A, ROCK 1, ROCK 2 not changed although myometrium thickness, uterine wet weight and the contractile responses of uterus increased in the PCOS group. The results suggest that the Rho-kinase inhibitors effectively suppressed increased contractions in the PCOS group they might be potential therapeutic agents.

OBJECTIVE To examine the effect of candesartan cilexetil with hydrochlorothiazide (6 mg and 12.5 mg, respectively) on blood pressure and ST-segment depression during daily life of patients with treated but not controlled arterial hypertension (blood pressure taken at doctor's practice (3)140/90 mmHg, despite being on at least two antihypertensive drugs) PATIENTS AND METHODS 51 patients (45 men, 17 women) with treated but reportedly uncontrolled hypertension were placed on self-measurement of blood pressure for 4 weeks of a run-in period and 8 weeks as a follow-up period. Combined 24-hour automatic blood pressure measurement (ABPM) and electrocardiography were done at the end of the run-in and the follow-up periods. Ten patients proved to be normotensive according to the self-measurement and ABPM after the run-in period (group A), while 41 were still uncontrolled according to both methods (group B). In group B the least efficacious component of the antihypertensive medication was replaced by candesartan with hydrochlorothiazide (C + HCT) and any changes in blood pressure and ST-segment depression analysed after 8 weeks of follow-up in both groups. RESULTS In group A no significant blood pressure change was observed between run-in- and follow-up periods. But in group B (n=41) the self-measured systolic blood pressure had significantly decreased (155/84 mmHg compared with [vs] 147/81 mmHg; p

This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI).The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats' cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months.PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1-4 of MWM testing (p 0.001). On day 2-4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3-4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms.Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance.

To investigate the antimuscarinic effect of oxybutynin in the rat detrusor muscle after estrogen pretreatment because, to our knowledge, no study has been done on the interaction of estrogen with antimuscarinic drugs. Estrogen has been shown to affect muscarinic receptors in the detrusor muscle of animals. In addition, oxybutynin has been shown to block muscarinic receptors in the bladder.Estradiol benzoate (150 microg/kg) or saline was given subcutaneously to virgin female Wistar albino rats (n = 6, each group) for 10 consecutive days. On the 11th day, isolated detrusor muscle strips were taken, and acetylcholine (ACh)-induced contractions were evaluated in the absence or presence of oxybutynin (10 and 100 nM).ACh induced concentration-dependent contractions in the detrusor muscle. In the estradiol-pretreated group, the maximum of the ACh-induced contractions was diminished compared with that in the control group (P0.05). Oxybutynin (10 and 100 nM) inhibited ACh-induced contractions competitively (pK(B) 8.85). In the estradiol-pretreated group, the concentration-response curve to ACh was shifted further to the right in the presence of oxybutynin (100 nM).We have demonstrated for the first time that oxybutynin further inhibits ACh-induced and muscarinic receptor-mediated contractions in rat detrusor muscle after pretreatment with estrogen.

In human internal mammary artery (IMA), testosterone induces vasodilation that shows marked variability among patients. We aimed to investigate the relationship of this variability with cardiovascular risk factors. Cumulative relaxations to testosterone after precontraction with KCl were examined in IMA segments from patients with identified cardiovascular risk factors such as hypercholesterolemia, diabetes, hypertension, smoking, age, gender, body mass index (BMI), and number of occluded vessels. Testosterone responses were significantly diminished in subjects with 3 compared with 1 risk factor. Hypercholesterolemia independently influenced testosterone responses by significantly decreasing its maximum, and smoking significantly decreased the sensitivity to testosterone. Thus, the variability observed in testosterone-induced vascular relaxations may in part be related to differences in risk factors present among the individuals studied.

Aim: The aim of the present study is to give a brief evaluation about plants used for the treatment of obstetric and gynecological conditions by using Cerrâhiyyetu’l-Hâniyye which has been written by Serefeddin Sabuncuoglu who was a famous surgeon in Anatolia in the 15th Century. Material and Methods: Based on the Cerrâhiyyetu’l-Hâniyye, we selected plants that used for women health, and systematically arranged plants according to diseases. Plant species that detected in this book compared with the plants of three works (Soranus’ On Gynecology, Paulus Aeginata’s The Seven Books, and Zahavi's At Tasrif). Results: Cerrâhiyyetu’l-Hâniyye contains 24 different medical plants for women health. Six plants were found in Cerrâhiyyetu’l-Hâniyye were different from the other books compared. Sabuncuoglu wrote 18 same plants which typed by other authors for women health. Conclusion: This study shade light on the Ottoman herbal remedy. Regard to plant treatment, difference between Cerrâhiyyetu’l-Hâniyye and other books submitted by the present study.

The objective of the present study was to investigate the prevalence, the risk factors, the hemodynamic triggering mechanisms, the circadian variability of ST segment depression (ST depression) and the effect of day and night fall in blood pressure on the prevalence of ST depression in hypertensive patients.In a multicentric study in Germany, 1,244 CardioTens registrations (combined 24-h ambulatory blood pressure measurement/electrocardiography with ST segment triggering; Meditech, Budapest, Hungary) from patients with arterial hypertension were consecutively monitored and evaluated centrally at the University of Bonn. Inclusion criterion was treated or untreated arterial hypertension. The ST segment was measured in accordance with the "1 : 1 : 1 rule" (horizontal or descending ST depression by 1 mm, 1 min duration, 1 min interval from the previous episode).ST segment depression was observed in 250 (20.1%) patients; 90.3% of the transient ST-segment depression was silent (without angina pectoris). Ambulatory 24-h blood pressure measurement, but not office-based blood pressure measurement, was predictive for the occurrence of ST-segment depression. Risk factors for ST-segment depression were the Sokolow indexor =3.5 mV, smoking status, severity of coronary heart disease, use of diuretics, reduced left ventricular function, pulse pressureor =60 mmHg and increase of double product (1,000 mmHg/min). A significant rise of the systolic/diastolic blood pressure (+8+ or -18/+7+ or -10 mmHg), of the heart rate (+12+ or -13/min) and of the double product (+2,471+ or -2,517 mmHg/min) was found during the transient ST depression as compared with the corresponding 24-h ambulatory blood pressure measurement mean values (P0.0001 for all parameters specified). In most intermittent ST depressions, a rise of the double product was seen (n=789 episodes), and in the remaining 239 ST depressions, a fall of the double product was observed. ST depressions with fall of the double product showed a circadian distribution with a peak in the late evening. ST depression accompanied by a rise in double product showed two peaks (one in the early morning and one in the late evening). The prevalence of ST depression was significantly higher (28.6%) in extreme dippers than in dippers (18.2%), risers (21.8%) and non-dippers (19.6%).ST depressions have a high prevalence of 20.1% in hypertensive patients. Clinical predictors for the occurrence of ST-segment depression were classical risk factors and cardiac target organ damage. Office-based blood pressure measurement was not a useful measuring tool for forecasting the likelihood of ST-segment depression. ST depressions were triggered inter alia by variations of blood pressure and the heart rate. The circadian variability of the ST depressions is crucially affected by the pressure double product characteristics on which the ST depression is based.