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: ObjectiveThe aim of this study was to investigate the effects of erythromycin on prostaglandin F2α (PGF2α)-induced contractions of isolated myometrial strips from non-pregnant rats.: DesignIn vitro pharmacological study.: SettingFirat University Faculty of Medicine.: SampleMyometrium samples were taken from 55 adult Wistar rats.: MethodsMyometrial strips were isolated from mature, non-pregnant Wistar rats. Isometric contractions of these strips were induced with 1 μM PGF2α. Effects of 0.01, 0.1, 0.2, 0.5 and 1 mM erythromycin on the frequency and amplitude of these PGF2α-induced contractions were recorded.: Main outcome measuresThe inhibition of prostaglandin F2α-induced contractions in vitro.: ResultsApplication of 0.01 mM erythromycin had no effect on either amplitude or frequency of contractions. However, 0.1, 0.2, 0.5 and 1 mM erythromycin decreased the frequency and amplitude of PGF2α-induced contractions. The inhibitory effect of erythromycin on amplitude was 27%, 38%, 54% and 83% (P < 0.05), and that on frequency was 10%, 16%, 32% and 61% (P < 0.05) at 0.1, 0.2, 0.5 and 1 mM concentrations, respectively.: ConclusionThe results of this study demonstrate that erythromycin inhibits PGF2α-induced contractions in rat myometrium. Because PGF2α-induced contractions have been suggested to be involved in the pathogenesis of primary dysmenorrhoea, effects of erythromycin in this clinical entity may present a new approach for the treatment. [Copyright &y& Elsevier]

A letter to the editor is presented which discusses a medical case study of a 72-year-old woman who has a basal cell carcinoma and its treatment.

Purpose: Ovarian cancer is the fifth leading cause of cancer related death in women. Platin-based doublet regimens plus bevacizumab is standard treatment in relapse. Due to formal regulation of Turkish Ministry of Health, adjuvant bevacizumab has not been reimbursed and clinicians can use bevacizumab at a dose of 7.5 mg/kg/3wk in platin-resistant and sensitive relapse settings. The primary aim of this study was to evaluate 7.5 mg/kg/3wk bevacizumab dosing in platin-resistant and sensitive relapse ovarian cancer and compare these findings with the current literature., Methods: A total of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included., Results: At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients died. Progression-free survival (PFS) and overall survival (OS) were estimated at 18.8 months (14.4-23.3) vs 29.7 months (24.3-35.1) of the whole group overall survival. We observed that 78.4% of patients treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients with debulking surgery relapsed. A significant number of patients (81%) treated with primary surgery without neoadjuvant treatment and 59 (76.6 %) had secondary debulking surgery at relapse. In relapse, 38 patients were treated with single agent liposomal doxorubicin (LPD) plus bevacizumab. On the other hand, 68 patients were treated with carboplatin and LPD plus bevacizumab. Multivariate analysis failed to show any clinicopathological characteristics with significant effect on PFS. However, cytoreductive surgery at relapse showed significant effect on OS. Bevacizumab-related toxicities were detected in 23 (21.7%) patients; hypertension, pulmonary embolism, perforation, and other toxicities (nephrotic syndrome in 2, osteonecrosis in 2, cerebrovascular and cardiac ischemia in 3 patients) were seen in 12 (11.3%), 3 (2.8%), 1 (0.9%) and 7 (6.6%) patients, respectively., Conclusions: In conclusion, our findings showed that 7.5 mg/kg/3week dosing of bevacizumab in relapsed ovarian cancer could have similar effectiveness compared to standard 15 mg/kg/3week dosing. Increase of OS and PFS in patients treated with primary and secondary debulking surgery with no-visible disease was more pronounced. No new safety information was observed but lower rate of grade 3 or above hypertension with similar rate of severe vascular and intestinal complications were detected.

Objective: To investigate the effect of circadian rhythm changes on fetal-placental development in pregnant rats., Material and Method: Pregnant rats were randomly allocated to 4 groups with 10 rats in each group. Group 1: 12 hours light 12 hours dark period (n:10, Control Group); Group 2: 6 hours light 6 hours dark period (n:10); Group 3: constant light group (n:10); Group 4: constant dark group (n:10). Rats were made to deliver by cesarean birth at the end of their pregnancy and their placenta, number and weight of the offspring, and placental histopathological changes were examined., Finding: Fetal number in the constant dark group was found significant in comparison to constant light group (p<0.01). Fetal weight in all groups with altered circadian rhythm was significantly lower than that in the control group (p<0.01). The decrease in fetal weight was more evident in the constant light group than in the constant dark group (p<0.01). Comparison of the histopathological findings of the placenta showed that placental edema, fibrin accumulation and leukocyte infiltration were significantly higher in constant light and constant dark groups than in other groups (p<0.01)., Conclusion: Circadian rhythm change in pregnancy adversely affects the fetal-placental development. More detailed studies are needed to clarify this mechanism.

Objective: Recent studies have concluded that an energy expenditure by an acute exercise session has no immediate effect on leptin levels while some showed a decline in leptin levels. The purpose of this study was to investigate any possible effects of training status of the subjects on acute exercise-leptin relationship in obese patients., Materials and Methods: Fourteen obese sedentary females were enrolled to the study and effects of acute incremental exercise on serum leptin levels were determined at rest and at maximal exercise performance. Then, they participated to a 12-weeks endurance aerobic training programme performed in the laboratory on a computer controlled cycle ergometer and their leptin levels were re-evaluated and the leptin-acute exercise relationships obtained under different training levels in the same group of subjects were compared. The body compositions were determined by bioelectrical impedance. Pre and post training blood samples were taken at rest and at the maximal exercise performance. Serum leptin levels were analysed in duplicate by RIA. Data were evaluated using, paired t and Pearson's tests., Results: Leptin levels were not acutely affected by the incremental exercise either before (23.62+/-3.5 ng/ml and 22.62+/-3.6 ng/ml) or after (13.13+/-3.4 ng/ml and 13.82+/-3.6 ng/ml) endurance training. The marked decrease in leptin levels following training was closely correlated with fat mass loss R= 0.899 (P= 0.0001)., Conclusions: This study indicates that an increase in energy expenditure by acute exercise has no significant acute effect on leptin level regardless of the training status of the subjects and decrease in leptin levels after a 12-weeks endurance aerobic training programme are closely associated with the fat mass loss.

Objective: To investigate the possible correlation between plasma malondialdehyde and homocysteine levels of preeclamptic patients., Design: Venous blood samples of 20 preeclamptics and 20 healthy pregnant controls were collected. Plasma malondialdehyde and homocysteine concentrations were measured and the correlation between them was investigated. Mann Whitney U test and Spearman correlation analysis were used for statistical analysis., Setting: University of Firat, Medical School., Results: Plasma malondialdehyde and homocysteine concentrations were higher in preeclamptic patients (p<0.05) and a positive correlation between these parameters was found (r: 0.77, p<0.01, n:20)., Conclusion: Our results may put forward some new strategies in the research of etiopathogenesis and treatment of preeclampsia.

Objectives: To comparatively investigate the effects melatonin and oxytetracycline as antioxidants on autologous intraperitoneal ovary transplantation in rats., Setting and Design: 28 adult female Wistar rats with regular estrous cycles were randomly divided into four groups. Group 1 (n=7) was the control group; Group 2 (n=7) bilateral oophorectomy and intraperitoneal transplantation group; and Groups 3 (n=7) and 4 (n=7) firstly received 20 mg/kg/IP melatonin and 10 mg/kg/IP oxytetracycline., respectively and fifteen minutes after that, they had bilateral oophorectomy and intraperitoneal transplantation. Ovarian tissue and blood malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) levels were determined. Vaginal cytology and ovarian necrosis were histopathologically investigated. Kruskall Wallis analysis of variance was used in the statistical analysis of data., Results: Ovarian necrosis, tissue MDA and plasma MDA levels were significantly higher in Group 2 compared to the Groups 1, 3 and 4 (p<0.03). SOD and GSHPx levels were significantly lower in group 2 compared to the groups 1, 3 and 4 (p<0.03). Melatonin was found to be more effective on ovarian necrosis and tissue MDA level than the use of oxytetracycline following autologous intraperitoneal ovary transplantation (p<0.03). There was a significant positive correlation between tissue MDA level and ovarian necrosis and a very strong negative correlation between tissue MDA and SOD level (rs = +/-0.9, n=28, p=0.000)., Conclusion: Although both melatonin and oxytetracycline were found to be effective in autologous intraperitoneal pelvic ovary transplantation, melatonin is more effective against both the ovarian necrosis and tissue MDA level in rats.

Objective: To investigate the use of omental graft following the repair of fistula between bladder and uterus (Youssef syndrome)., Methods: Primary repair was performed on four women who had developed vesico-uterine/vesico-cervical fistula and infertility due to previous low segment caeserean between October 1997 and January 2001. An omental graft of 4cm x 3.5cm was placed between bladder and uterus., Results: Repair was successful in all four patients. Complaints of amenorrhea, menouria and in three patients urine-type vaginal flux disappeared. Three patients did not want pregnancy, so contraceptives were administered. The fourth patient conceived after 4 months., Conclusions: This operation is both simple and effective. Fertility is recovered quickly.

Objective: The aim of this study was to investigate the effects of erythromycin on prostaglandin F2alpha (PGF2alpha)-induced contractions of isolated myometrial strips from non-pregnant rats., Design: In vitro pharmacological study., Setting: Firat University Faculty of Medicine., Sample: Myometrium samples were taken from 55 adult Wistar rats., Methods: Myometrial strips were isolated from mature, non-pregnant Wistar rats. Isometric contractions of these strips were induced with 1 microM PGF2alpha. Effects of 0.01, 0.1, 0.2, 0.5 and 1 mM erythromycin on the frequency and amplitude of these PGF2alpha-induced contractions were recorded., Main Outcome Measures: The inhibition of prostaglandin F2alpha-induced contractions in vitro., Results: Application of 0.01 mM erythromycin had no effect on either amplitude or frequency of contractions. However, 0.1, 0.2, 0.5 and 1 mM erythromycin decreased the frequency and amplitude of PGF2alpha-induced contractions. The inhibitory effect of erythromycin on amplitude was 27%, 38%, 54% and 83% (P < 0.05), and that on frequency was 10%, 16%, 32% and 61% (P < 0.05) at 0.1, 0.2, 0.5 and 1 mM concentrations, respectively., Conclusion: The results of this study demonstrate that erythromycin inhibits PGF2alpha-induced contractions in rat myometrium. Because PGF2alpha-induced contractions have been suggested to be involved in the pathogenesis of primary dysmenorrhoea, effects of erythromycin in this clinical entity may present a new approach for the treatment.

Objective: The aim of this study was to investigate the effects of erythromycin on pregnancy duration and on live birth weight in lipopolysaccharide (LPS)-induced preterm labor model in rats., Study Design: Total of 60 pregnant rats on day 16 of gestation was intraperitoneally injected with 25 microg/kg LPS. Animals were randomly divided into six groups and 20mg/kg (n=10), 40 mg/kg (n=10), 60 mg/kg (n=10), 80 mg/kg (n=10), and 100mg/kg (n=10) erythromycin and equal volume of physiological saline (n=10) were given intraperitoneally. Injection of LPS-to-vaginal bleeding interval, vaginal bleeding-to-delivery interval, LPS injection-to-delivery interval was monitored and live birth weight of neonates was determined. Statistical analysis was performed using Kruskal-Wallis, Mann-Whitney U-test and Spearman correlation analysis., Results: Intraperitoneal injection of erythromycin to LPS-administered rats caused significant increase in latent period, labor period, total period and live birth weight in a dose dependent manner., Conclusion: These data shows that erythromycin causes prolongation of pregnancy period and increases live birth weight in LPS-induced preterm labor of pregnant rats.

Recent studies have suggested association between the elevated homocysteine levels and pregnancy complications. The aim of this study was to investigate the effects of homocysteine on spontaneous contractions of myometrium isolated from pregnant guinea pig. Full-thickness myometrial strips were obtained from late-pregnant guinea pigs following decapitation, and suspended in an organ bath which was filled with physiological saline solution (pH 7.4), maintained at 37 degrees C and continuously bubbled with 95% O2 and 5% CO2. After the observation of spontaneous contractions under one gram of resting tension, homocysteine (0.2, 0.5 and 1 mM) was added to the organ bath and effects of this agent on frequency and amplitude of contractions were evaluated in 20-min periods. One-way analysis of variance was used for statistical analysis of the data. Homocysteine caused increase in both frequency and amplitude of spontaneous contractions in a dose-dependent manner. The results from this in vitro study indicate that cardiovascular risk factor homocysteine has contracting pharmacological effects on guinea pig myometrium.

Objectives: Pulmonary edema has been shown to occur following ischemia-reperfusion injury in a variety of organs and effects of several pharmacological agents on ischemia-reperfusion-induced damage has been investigated previously. However, there are only a few studies in the literature about pulmonary injury following adnexial ischemia-reperfusion. In this study we aimed at investigating pulmonary changes following adnexial ischemia-reperfusion and the effects of melatonin on noncardiogenic pulmonary edema secondary to adnexial ischemia-reperfusion., Methods: A total of 32 Dunkin-Harley guinea pigs were randomly divided into four groups. In group I, oopherectomy was performed following adnexial torsion of three hours (ischemia). Adnexial torsion of three hours followed by a 3 hours detorsion period (reperfusion) and then oopherectomy was performed in remaining three groups. No therapy was given in group one and two while isotonic saline and melatonin was applied intraperitoneally in groups three and four, respectively. Serum malondialdehyde (MDA) levels of operated ovaries and lungs and polimorphonuclear leucocyte infiltration of lungs were determined., Results: MDA levels in serum, ovary and lungs were higher in detorsion groups (groups II, III) than torsion group (group I) (p<0.01). Melatonin administration significantly decreased the polimorphonuclear leukocytes infiltration of lung parenchime and MDA levels in serum, ovaries and lungs (groups II and IV; groups III and IV; p<0.01, p<0.01). MDA levels and lung tissue PNL infiltration levels of melatonin administered detorsioned group was similar to those levels of only salphingo-oopherectomy performed group (Group I and IV, p>0.05)., Conclusion: Pathophysiology of ischemia-reperfusion must be considered in the cases of adnexial torsion where detorsion is thought. As an antioxidant, melatonin administration might be helpful in decreasing post-operative morbidity by decreasing reperfusion injury of lungs.