Mehmet Güney

Endometrial apoptosis induced by a 900-MHz mobile phone: Preventive effects of vitamins E and C

Numerous reports have described the effects induced by an electromagnetic field (EMF) in various cellular systems. The purposes of this study were to examine oxidative stress that promotes production of reactive oxygen species induced by a 900-megahertz (MHz) mobile phone and the possible ameliorating effects of vitamins E and C on endometrial tissue against EMF-induced endometrial impairment and apoptosis in rats. Animals were randomly grouped as follows: (1) sham-operated control group (n=8), (2) 900 MHz EMF-exposed group (n=8; 30 min/d for 30 d), and (3) 900 MHz EMF-exposed group, treated with vitamins E and C (n=8; 50 mg/kg intramuscularly and 20 mg/kg body weight intraperitoneally before daily EMF exposure). Malondialdehyde (an index of lipid peroxidation) was used as a marker of oxidative stress-induced endometrial impairment; Bcl-2, Bax, caspase-3, and caspase-8 were assessed immunohistochemically. In this study, increased malondialdehyde levels in endometrial tissue and apoptosis illustrated the role of the oxidative mechanism induced by exposure to a 900-MHz mobile phone-like device and vitamins E and C; via free radical scavenging and antioxidant properties, oxidative tissue injury and apoptosis were ameliorated in rat endometrium. In conclusion, exposure to 900-MHz radiation emitted by mobile phones may cause endometrial apoptosis and oxidative stress, but treatment with vitamins E and C can diminish these changes and may have a beneficial effect in preventing endometrial changes in rats.

900 MHz radiofrequency-induced histopathologic changes and oxidative stress in rat endometrium: protection by vitamins E and C

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Mechanisms of adverse effects of EMR indicate that reactive oxygen species (ROS) may play a role in the biological effects of this radiation. The aims of this study were to examine 900 MHz mobile phone-induced oxidative stress that promotes production of ROS and to investigate the role of vitamins E and C, which have antioxidant properties, on endometrial tissue against possible 900MHz mobile phone-induced endometrial impairment in rats. The animals were randomly grouped (eight each) as follows: 1) Control group (without stress and EMR, Group I), 2) sham-operated rats stayed without exposure to EMR (exposure device off, Group II), 3) rats exposed to 900MHz EMR (EMR group, Group III) and 4) a 900MHz EMR exposed + vitamin-treated group (EMR + Vit group, Group IV). A 900 MHz EMR was applied to EMR and EMR + Vit group 30min/day, for 30 days using an experimental exposure device. Endometrial levels of nitric oxide (NO, an oxidant product) and malondialdehyde (MDA, an index of lipid peroxidation), increased in EMR exposed rats while the combined vitamins E and C caused a significant reduction in the levels of NO and MDA. Likewise, endometrial superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased in EMR exposed animals while vitamins E and C caused a significant increase in the activities of these antioxidant enzymes. In the EMR group histopathologic changes in endometrium, diffuse and severe apoptosis was present in the endometrial surface epithelial and glandular cells and the stromal cells. Diffuse eosinophilic leucocyte and lymphocyte infiltration were observed in the endometrial stroma whereas the combination of vitamins E and C caused a significant decrease in these effects of EMR. It is concluded that oxidative endometrial damage plays an important role in the 900 MHz mobile phone-induced endometrial impairment and the modulation of oxidative stress with vitamins E and C reduces the 900MHz mobile phone-induced endometrial damage both at biochemical and histological levels. Toxicology and Industrial Health 2007; 23: 411—420.

Protective effects of vitamins C and E against endometrial damage and oxidative stress in fluoride intoxication.

1 Fluoride (F) is an essential trace element that has protective effects against bone mineral loss. However, it becomes toxic at higher doses and induces some adverse effects on a number of physiological functions, including reproduction. The aims of this study were to examine F‐induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of vitamins C and E against possible F‐induced endometrial impairment in rats. 2 Rats were divided into three groups: control, F and F plus vitamins. The F group was given 100 mg/L orally for 60 days. Combined vitamins were also administered orally. Fluoride administration to control rats significantly increased endometrial malondialdehyde (MDA) but decreased superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and catalase (CAT) activities. Endometrial glandular and stromal apoptosis were investigated by DNA nick end‐labelling (TUNEL) method on each sample and the mean endometrial apoptotic index (AI) was calculated. 3 Vitamin administration with F treatment caused endometrial MDA to decrease, but SOD, GSH‐Px and CAT activities to increase, all to significant levels. Vitamins showed a histopathological protection against F‐induced endometrial damage. There was a significant difference in the AI between the groups. Lymphocyte and eosinophil infiltration in stroma in F‐treated rats were more than those in the control and F + Vit groups. 4 It can be concluded that oxidative endometrial damage plays an important role in F‐induced endometrial toxicity, and the modulation of oxidative stress with vitamins reduces F‐induced endometrial damage both at the biochemical and histological levels.

Effects of metformin on mammalian target of rapamycin in a mouse model of endometrial hyperplasia.

OBJECTIVE The effects of metformin on S6K1, which is a crucial effector of mTOR signaling, and on endometrium were studied in a mouse model of endometrial hyperplasia induced by unopposed estradiol or tamoxifen. STUDY DESIGN Forty-eight oophorectomized Balb/c mice were randomly assigned to receive saline, tamoxifen citrate (4 mg/kg), 17-beta estradiol hemihydrate (4 mg/kg), metformin (50 mg/kg), tamoxifen citrate (4 mg/kg) with metformin (50 mg/kg), or estradiol (4 mg/kg) with metformin (50 mg/kg) for 3 days. Histological markers of uterotrophy, including luminal epithelial cell height and density of endometrial glands were quantified for each slide. Immunohistochemical expression of PCNA and S6K1 was evaluated. H-score was used for S6K1 expression. Statistical analysis was performed using Students t-test for comparison of two continous variables and one-way ANOVA for comparison of multiple variables. RESULTS Mice treated either with tamoxifen or estradiol had significantly increased density of endometrial glands and epithelial heights compared to vehicle-only or metformin-only group (p<0.001). Addition of metformin to tamoxifen or estradiol treated mice significantly decreased the density of endometrial glands and epithelial cell heights (p<0.05). Addition of metformin to tamoxifen significantly decreased the H-score of S6K1 (p<0.05) and the immunohistochemical expression of PCNA (p<0.05) in uterine lining epithelium, glandular and stromal cells. Addition of metformin to estradiol significantly decreased the H-score of S6K1 (p<0.05) and the immunohistochemical expression of PCNA (p<0.05) in uterine lining epithelium, glandular and stromal cells. CONCLUSION Metformin seems to have possible antiproliferative effects on the endometrium of estradiol or tamoxifen treated mice via inhibiting the mTOR mediated S6K1 activation.

Placenta accreta associated with a ruptured pregnant rudimentary uterine horn

Abstract Pregnancy in a rudimentary uterine horn is rare and is usually associated with fetal death and serious maternal morbidity and mortality. A case of pregnancy in a rudimentary uterine horn with rupture 14 weeks after last menstrual period and is complicated with placenta accreta is presented. The patient had signs and symptoms of massive hemoperitoneum. An emergency exploratory laparotomy revealed rupture of the gravid rudimentary horn of a bicornuate uterus. Histologic examination of the specimen showed that placenta was accreta. The relative literature is reviewed and the association of placenta accreta in such situations is pointed out.

Ovarian toxicity in rats caused by methidathion and ameliorating effect of vitamins E and C

We have investigated the effect of subchronic administration of methidathion (MD) on ovary evaluated ameliorating effects of vitamins E and C against MD toxicity. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD + Vit group). MD and MD + Vit groups were given MD by gavage five days a week for four weeks at a dose level of 5 mg/kg/day by using corn oil as the vehicle. Serum malondialdehyde (MDA: an indicator of lipid peroxidation) concentration, serum activity of cholinesterase (ChE), and ovary histopathology were studied. The level of MDA increased significantly in the MD group compared with the control (P < 0.005). Serum MDA decreased significantly in the MD + Vit group compared with the MD group (P < 0.05). The activities of ChE decreased significantly both in the MD and MD + Vit groups compared with the controls ( P < 0.05). However, the decrease in the MD + Vit groups was less than in the MD group; the ChE activity in the MD + Vit group was significantly higher compared with MD group (P < 0.05). Number of ovarian follicles were significantly lower in the MD group compared to the controls (P < 0.05). Number of atretic follicles were significantly higher in the MD group than in the controls (P < 0.05). Follicle counts in MD + Vit group showed that all types of ovarian follicles were significantly higher, and a significant decrease in the number of atretic follicles compared with the MD group (P < 0.05). In conclusion, subchronic MD administration caused an ovarian damage, in addition, LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Treatment with vitamins E and C after the administration of MD reduced LPO and ovarian damage. Human & Experimental Toxicology (2007) 26 , 491—498

Effect of caffeic acid phenethyl ester on the regression of endometrial explants in an experimental rat model.

The objective of this study is to determine the effects of antioxidant and anti-inflammatory caffeic acid phenethyl ester (CAPE) on experimental endometriosis, peritoneal superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) levels in the rat endometriosis model. Thirty rats with experimentally induced endometriosis were randomly divided into 2 groups and treated for 4 weeks with intraperitoneal CAPE (CAPE-treated group; 10 µmol/kg/d, n = 13) or vehicle (control group; n = 13). The volume and weight changes of the implants were calculated. Immunohistochemical and histologic examinations of endometriotic explants by semiquantitative analysis and measurements of peritoneal SOD, CAT, and MDA levels were made. Following 4 weeks of treatment with CAPE, there were significant differences in posttreatment spherical volumes (37.4 ± 14.7 mm3 vs 147.5 ± 41.2 mm3) and explant weights (49.1 ± 28.5 mg vs 158.9 ± 50.3 mg) between the CAPE-treated groups and controls. The mean evaluation nomogram levels in glandular epithelium for COX-2 positivity by scoring system were 2.1 ± 0.3 in the CAPE-treated group and 3.9 ± 0.3 in the control group. In the CAPE-treated group, peritoneal levels of MDA and activities of SOD and CAT significantly decreased when compared with the control group (P < .01). Histologic analysis of the explants demonstrated mostly atrophy and regression in the treatment group, and semiquantitative analysis showed significantly lower scores in rats treated with CAPE compared with the control group. CAPE appeared to cause regression of experimental endometriosis.

Expression of cyclooxygenase-2, matrix metalloproteinase-2 and matrix metalloproteinase-9 in premenopausal and postmenopausal endometrial polyps.

OBJECTIVES Cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) are influenced by relative levels of estrogen and are involved in promoting cell proliferation and angiogenesis. The present study investigated expression of COX-2, MMP-2 and MMP-9 in endometrial polyps from premenopausal and postmenopausal women. METHODS Premenopausal (n=18) and postmenopausal (n=22) endometrial polyps were included in the study. None of the women were using non-steroid anti-inflammatory drugs, hormone replacement therapy or any other estrogen containing pills. Immunohistochemical analysis for MMP-2, MMP-9 and COX-2 were performed on formalin fixed, paraffin-embedded tissue using the streptavidin-biotin-peroxidase technique. The cut-off value for positiviy was set to 10% and staining more than 50% was regarded as intense staining. Staining of 10-25% and 25-50% were recorded as mild and moderate, respectively. RESULTS COX-2, MMP-2 and MMP-9 were stained in epithelial cells and stroma of premenopausal and postmenopausal endometrial polyps. Stromal expression of COX-2, MMP-2 and MMP-9 were found significantly higher in premenopausal polyps compared to postmenopausal polyps (p<0.05). There were no other significant differences in the immunohistochemical expressions in the epithelium of premenopausal and postmenopausal endometrial polyps except MMP-9. CONCLUSION Polyps from both premenopausal and postmenopausal women express epithelial and stromal COX-2, MMP-2 and MMP-9, however immunohistochemical expression of these markers may be different due to menopausal status. This may suggest a shared pathogenesis for pre- and postmenopausal endometrial polyps.

Intravesical migration of intrauterine device resulting in pregnancy

Abstract  Spontaneous migration of an intrauterine device into the bladder is very rare. A 29‐year‐old woman in whom an intrauterine device had been placed 6 years previously, presented complaining of chronic pelvic pain and recurrent irritative urinary tract symptoms. One year after insertion she had became pregnant and given birth without complications. Intravesical migration of the intrauterine device was confirmed by sonography and cystoscopy. The intrauterine device was removed by suprapubic cystostomy.

Efficacy of intrauterine lidocaine for removal of a "lost" intrauterine device: a randomized, controlled trial.

OBJECTIVE: To evaluate the efficacy of intrauterine lidocaine instillation in reducing patient discomfort during the removal of a “lost” intrauterine device (IUD). METHODS: This double-blinded, randomized, placebo-controlled trial included 68 women who underwent removal procedure for a “lost” IUD. Thirty-four women were allocated to the lidocaine group and 34 to the saline group. The main outcome measure was the intensity of pain during, immediately after, and 20 minutes after the procedure, assessed by a visual analog scale. Statistical analysis was performed using the Friedman test with Bonferroni correction, Student t test, and &khgr;2. RESULTS: There were no statistically significant differences between the study group and the control group in mean age, parity history of chronic pelvic pain and dysmenorrhea, history of curettage, education, socioeconomic status, menopausal status, breastfeeding, type of IUD, and duration of IUD. Pain scores demonstrated a significant difference between groups during the procedure (placebo 6.41 ± 1.15, lidocaine 5.23 ± 0.69, P < .01), immediately after procedure (placebo 6.05 ± 1.01, lidocaine 4.94 ± 0.60, P < .01), and 20 minutes after procedure (placebo 4.32 ± 0.63, lidocaine 4.44 ± 0.66, P < .01). The number needed to treat was 3 (95% confidence interval 2–9). CONCLUSION: Intrauterine lidocaine appears to be effective in decreasing pain in women undergoing the removal procedure of a “lost” IUD. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT00308841. LEVEL OF EVIDENCE: I