Ganoderma lucidum and Hypericum perforatum Exhibit Anti-Inflammatory, Antioxidant, and Anti-Androgen Effect in Rat Model of Experimental Polycystic Ovarian Syndrome.

OBJECTIVE: Chronic inflammation is considered to be of key importance in the pathogenesis of polycystic ovarian syndrome (PCOS). Ganoderma lucidum polysaccharide (GLP) and Hypericum perforatum (HP) have been reported to have anti-inflammatory and antioxidant activities. We studied the effects of these agents on ovarian tissue in a rat model of experimental PCOS. MATERIALS AND METHODS: Forty-two Sprague-Dawley female rats were divided into 6 groups with 7 animals in each group as listed below: Group 1: Control, Group 2: PCOS, Group 3: PCOS + HP, Group 4: HP only, Group 5: PCOS+ GLP, Group 6: GLP only. At the end of the experimental procedures, all the animals underwent bilateral oophorectomy and blood samples were collected. Ovarian tissue and blood samples were used for biochemical and histopathological analysis. RESULTS: Follicle degeneration in the PCOS group showed a statistically significant increase compared to the other groups (p < 0.05). Cystic follicles were significantly reduced in the PCOS+GLP and PCOS+HP groups as compared to the PCOS group. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were elevated in PCOS rats (p < 0.01). Levels of sex hormone binding globulin (SHBG) levels were diminished (p < 0.01). Levels of malondialdehyde (MDA) and insulin-like growth factor 1 (IGF-1) were increased in PCOS rats as compared to the other groups (p < 0.02, p < 0.02, respectively). GLP supplementation diminished the levels of IGF-1 and MDA. GLP or HP supplementation increased reduced glutathione (GSH). CONCLUSION: GLP and HP treatment normalizes SHBG levels while correcting PCOS-induced hyperandrogenemia. Both herbs regulate the redox balance by decreasing the levels of MDA and increasing the level of GSH.

VEGF I/D variant and preeclampsia risk in Turkish women: a case-control study.

Preeclampsia (PE) is a systemic vascular disorder, is caused by an imbalance of pro- and anti-angiogenic factors that directly affect endothelial function. Vascular endothelial growth factor A (called VGF), a pro-angiogenic factor associated with endothelial dysfunction, plays an important role in the pathophysiology of PE. Therefore, we investigated the relationship between -2549 insertion/deletion (I/D) variant in the VEGF promoter region and PE in pregnant women in Turkey. A total of 100 patients diagnosed with PE and 118 healthy pregnants were recruited. To genotype the VEGF I/D variant, the PCR method was used. The results of analyses were evaluated for statistical significance. The weight of the PE group was found to be higher before and after pregnancy than the control group (p = 0.009, p = 0.012, respectively). The birth weight, and Apgar score (1 min and 5 min) of the PE group was lower than that of the control group (p= <0.001, p= <0.001, p= <0.001, respectively). The mean 24-h urine protein, ALT and AST levels in the PE group were higher than the control group (p= <0.001, p= <0.001, p= <0.001, respectively). There was no significant difference between the patients and the controls in terms of VEGF I/D genotype and allele distribution. There was no deviation from HWA for VEGF I/D variant in patient and control groups. In the patients carrying D/D genotype and the D allele had low gestational week and birth weight. Knowing the risk factors for PE is very important for its prevention and treatment. In conclusion, for the first time, our results supported that the VEGF I/D variant is not a risk factor for the development of PE in a group of Turkish populations. But VEGF I/D variant D/D genotype associated with low gestational week and birth weight while I/D genotype seems to be protective from high systolic blood pressure.

The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study.

BACKGROUND: Endometriosis is a chronic inflammatory pathology that can cause persistent pelvic pain and infertility by affecting women of reproductive age. It is defined as the placement of endometrial tissue outside the uterine cavity. Hormonal, genetic and immunological factors have an effect on the development of endometriotic implants. Adalimumab is a monoclonal antibody specific for tumor necrosis factor alpha (TNF-á), used in the treatment of autoimmune diseases. OBJECTIVES: To investigate the effectiveness of adalimumab on histopathological and biochemical values in rats with experimental endometriosis. MATERIAL AND METHODS: This study is a comparative, prospective, experimental rat study. Wistar albino female rats were divided into 4 groups. Group 1 was separated as the control group. Endometriotic implants were simultaneously induced in group 2 and group 3. After 4 weeks, developing endometriotic foci were measured. Adalimumab (5 mg/kg) was simultaneously intraperitoneally (ip.) administered to group 3 and group 4 for 4 weeks. At the end of the study, histopathological scoring and fibrillin-1 scoring were performed. Total antioxidant status (TAS), total oxidant status (TOS) and malondialdehyde (MDA) values were measured. Findings in all groups were compared. RESULTS: When group 1 and group 2 were compared, the histopathological score, as well as MDA and TOS levels increased, while TAS levels decreased in group 2 (p < 0.001). After adalimumab treatment, the average endometriotic implant size in group 3 (0.32 ±0.002 mm) decreased compared to group 2 (0.77 ±0.04 mm) (p = 0.032). While fibrillin-1 score increased in group 2 and group 3 compared to group 1, it decreased in group 3 compared to group 2 (p < 0.001). Histopathological score decreased, TAS levels increased and MDA levels decreased in group 3 compared to group 2 (p < 0.001). CONCLUSIONS: Adalimumab may play a role in the regression of endometrial implants by showing antioxidant and anti-inflammatory effects on histopathological damage and fibrosis.

The effect of carbamazepine, which increases oestrogen destruction, on the endometriotic implants; an experimental rat model.

We planned this experimental study to investigate the effect of carbamazepine (CMZ) on the endometriotic implants. Rats were randomised into four groups after endometriosis surgery. Drinking water was given to the sham group, 0.2 mg/kg oestradiol valerate (EV) to the EV group, 100 mg/kg/day CMZ to the CMZ group, and 0.2 mg/kg EV and 100 mg/kg/day CMZ to the EV-CMZ group. The endometrium of the rats using CMZ stained more intensely with cytochrome P450-3A4 (CYP3A4) enzyme. No endometrial hyperplasia was found in these rats. Endometriotic implants weight was found to be higher in these rats. There was no difference between the groups in terms of staining of the endometriotic implants with CYP3A4 enzyme. Endometriotic implants were less stained with the CYP3A4 enzyme than the endometrium. According to our results, CMZ does not increase the destruction of oestrogen in the endometriotic implants, unlike the endometrium. It may even cause the lesion to enlarge.Impact statementWhat is already known on this subject? Endometriosis is an oestrogen-dependent, progressive disease. Carbamazepine (CMZ) is known to increase oestrogen degradation by activating the cytochrome P450-3A4 (CYP3A4) enzyme. CMZ can be used in the treatment of endometriosis because it increases oestrogen breakdown in tissues.What do the results of this study add? CMZ can protect the endometrium against hyperplasia by increasing the amount of CYP3A4 enzyme in the endometrium. This effect could not be demonstrated in the endometriotic implants. The presence of CYP3A4 enzyme less in the endometriotic implants than in the endometrium may explain this situation. In addition, the fact that CMZ does not increase the enzyme in the endometriotic implants may contribute to this situation.What are the implications of these findings for clinical practice and/or further research? CMZ may not be a suitable alternative in the treatment of endometriosis. However, it may protect against endometrial hyperplasia. Clinical studies are needed for this effect.

Effects of Different Progesterone Doses on the Concentrations of Proinflammatory and Anti-inflammatory Cytokines in Pregnant Women With Threatened Abortion.

Background and objective This study aimed to investigate how different doses of progesterone influence the concentrations of interleukin-6 (IL-6) and tumor necrotizing factor-alpha (TNF-α), which are proinflammatory cytokines, as well as that of IL-10, which is an anti-inflammatory cytokine, in pregnant women with threatened abortion. Materials and methods This is a prospective, single-center, randomized controlled trial conducted with 221 patients with a threatened abortion diagnosis. Group 1 consisted of IL-6, IL-10, and TNF-α values in pre-treatment blood samples from 221 patients diagnosed with imminent abortion. Group 2 included 81 patients who received natural oral 100 mg micronized progesterone MP twice a day for two weeks. Group 3 included 83 patients who were administered oral 200 mg of natural micronized progesterone MP twice a day for two weeks. Group 4 included 57 patients who received oral 200 mg of natural micronized progesterone MP twice a day for two weeks, and one depot progesterone was added to the treatment by administering it at a dosage of 500 mg/day intramuscularly. Results IL-6 values between groups were lower in group 4 compared to group 3 (p=0.007). When IL-10 values were compared between the groups, the IL-10 ratio was highest in group 4 and lowest in group 2 (p<0.001, p=0.003, p<0.001). When the TNF-α values between the groups were compared, the value in group 4 was decreased compared to groups 1 and 2 (p=0.031, p<0.001). In the logistic regression analysis, the IL-6 value above 12.01 increased the abortion imminens rate 1.01 times, and a TNF-α value above 11.04 increased the abortion imminens rate 1.21 times. Conclusion Progesterone used to treat imminent abortion reduces the levels of proinflammatory cytokines, such as IL-6 and TNF-α, while increasing those of anti-inflammatory cytokine IL-10 in proportion to the dose administered. Progesterone can prevent imminent abortion by generating an anti-inflammatory environment.

Histopathological Examination of the Mucosal Effects of Obstetric Gel on Vaginal Wound Healing in an Incision-Inflicted Rat Model.

Background and objective The present study intended to investigate the histopathological efficacy of obstetric gels on the healing of vaginal lacerations in rats. To the best of our knowledge, this is the first such study. Materials and methods Twenty-one female Wistar albino rats were divided into three groups, comprising seven animals per group. The first group (group 1) was the control group, the second (group 2) was the polyvinyl iodine (PI) group, and the third group (group 3) was the obstetric gel (OG) group. In all three groups, a vaginal incision was made with a No. 10 scalpel, and the incision site was sutured with a 3-0 Vicryl suture. In the control group, the incision site was left for routine healing. The incision site was washed with PI in the PI group and with OG in the OG group. After 15 days, vaginal tissues were obtained from all three groups for histopathological examination. In addition, immunohistochemistry staining was performed using caspase 3 and fibrillin 1 antibodies. Results There was no significant difference between the groups in terms of congestion, vascular proliferation, and inflammation stages in the examinations performed on the vaginal wall. However, the amount of collagen and elastic fibers increased during the remodeling and fibrosis phase, and the fibrillin 1 score increased in immunohistochemistry staining (p < 0.001). Conclusion It has been shown in rat vaginal tissue that obstetric gels do not have negative effects on wound healing; however, they contribute to wound healing by positively affecting the fibrosis stage.

Vitamin D improves oxidative stress and histopathological damage in rat ovaries caused by hyperthyroidism.

OBJECTIVE: The aim of this study is to investigate the histopathological and biochemical efficacy of vitamin D on oxidative damage and fibrosis in rat ovaries induced by experimental hyperthyroidism. METHODS: This study is a comparative, prospective experimental rat study. Sprague-Dawley female rats were divided into four groups. Only distilled water was given to the rats in group 1 for 25 days. In group 2, 100 µg/day L-thyroxine was given to rats for 25 days. In Group 3, 100 µg/day L-thyroxine and 200 IU/day vitamin D were given to rats for 25 days. In group 4, only 200 IU/day vitamin D was administered for 25 days. RESULTS: This study is the first to demonstrate the protective effect of vitamin D against ovarian damage caused by experimental hyperthyroidism. Hyperthyroidism caused fibrotic degenerative changes in the ovaries and an increase in the fibrillin 1 score. It caused serum follicle-stimulating hormone (FSH) levels to increase and serum E2 levels to decrease. In addition, malondialdehyde (MDA) and total oxidant status (TOS) levels increased in rats with hyperthyroidism. Vitamin D decreased MDA and TOS values and increased total antioxidant status (TAS) values in rats with hyperthyroidism. It also increased TSH values by causing a decrease in TT3 and TT4 values. It decreased fibrosis, follicle degeneration, stromal degeneration, and fibrillin 1 score in ovarian tissue. CONCLUSION: Vitamin D has positive histopathological and biochemical effects on the oxidative stress and follicle damage caused by hyperthyroidism in ovarian tissue. Human studies with larger case populations should be conducted to evaluate the effects and clinical applications of vitamin D.

Can complete blood count parameters that change according to trimester in pregnancy be used to predict severe preeclampsia?

We aimed to evaluate the effectiveness of changes over time in complete blood count (CBC) parameters to estimate the diagnosis of preeclampsia. Data on 161 severe preeclampsia patients and 161 healthy pregnant patients who met the study criteria of pregnant women whose CBC had been measured at 10-12, 22-24 and 28-30 weeks of pregnancy were compared. In the preeclampsia group, an increase in the mean platelet volume (MPV) value and a decrease in the number of platelets were statistically significant in the transition from the second to the third trimester. MPV and lymphocyte counts were more significant in the third trimester and neutrophil lymphocyte ratio (NLR) were more significant in the second trimester. We found that evaluation of the changes in lymphocyte, MPV and NLR values in three different trimesters of pregnancy rather than a single trimester was more meaningful to predict severe preeclampsia.Impact StatementWhat is already known on this subject? Studies have shown that MPV and NLR can predict preeclampsia. However, a clear cut off value could not be determined. The reasons for this may be that the gestational week during which the measurement is made is not standard and the patient groups are not homogeneous.What the results of this study add? In this study, CBC parameters at different stages of the preeclampsia process were compared in the severe preeclampsia group. According to our results, lymphocytes, NLR and MPV can be used to predict severe preeclampsia. In addition, NLR measurements in the second trimester and MPV and lymphocyte measurements in the third trimester were found to be more significant in predicting severe preeclampsia.What the implications are of these findings for clinical practice and/or further research? In order to predict severe preeclampsia, instead of a single measurement of CBC parameters, new calculations should be made that add change over time.

The parameters affecting the success of uterus-sparing surgery in cases of placenta adhesion spectrum disorder.

OBJECTIVE: This study aimed to evaluate the parameters affecting the treatment success of conservative surgery in cases with placental invasion anomaly. METHODS: Archive files and digital image records of 67 patients with placental invasion anomaly were studied. The patients were divided into two groups, a conservative surgery group and a cesarean hysterectomy group. Demographic data, cervical length, placental localization, placental surface area adhering to previous cesarean section line, preoperative and postoperative hematocrit values, transfused blood products, and surgical complications were compared between the two groups. RESULTS: In the conservative surgery group, the cervical length was longer (p < .001) and the surface area of the placenta in the previous cesarean scar line was smaller (p < .001). For cervical length, the sensitivity and specificity values were 97 and 81%, respectively, when the cut-off value was 35.5 mm. When the cut-off value for the placental surface area in the previous cesarean scar line was 85.5 cm2, the sensitivity and specificity values were 68 and 72%, respectively. In the caesarean hysterectomy group, the preoperative and postoperative hematocrit values were lower (p < .001, p = .003, respectively), and the amount of transfused erythrocyte suspension and fresh frozen plasma were higher (p < .001, p = .001, respectively). CONCLUSION: In this study, it was concluded that the presence of the nondestructive intact cervical tissue, in the cases with placental invasion anomaly and/or the small size of the placental surface area adhering to the previous cesarean scar line, increase the feasibility of conservative surgery.

The effect of vaginal bleeding and non-spesific pelvic pain on pregnancy outcomes in subchorionic hematomas cases.

OBJECTIVES: To determine the clinical differences and factors affecting early pregnancy outcome in the first and early secondtrimester subchorionic hematoma cases. MATERIAL AND METHODS: This study involved with the retrospective analysis and evaluation of 81 cases diagnosed withsubchorionic hematoma. The patients were grouped according to the gestational periods, symptoms at the time of admission,ratio of surrounding hematoma to the gestational sac, and whether there was a pregnancy loss. The groups werecompared according to the clinical features and pregnancy outcomes. RESULTS: The ratio of surrounding hematoma to the gestational sac in the group with pregnancy loss was significantly higher(p = 0.002). When the cut-off value was 35.5%, it could determine the possibility of a complication in pregnancy with 70%sensitivity and 75% specificity. Nonspecific pelvic pain were significantly higher in the pregnancy loss group than in theother group. Logistic regression analysis was performed to determine the effect of these two parameters on the pregnancyoutcome. Although the presence of non-specific pelvic pain is more in the group with pregnancy loss; there was no effectof on pregnancy outcome (p = 0.141). The risk of pregnancy loss increased 4.5 fold if the ratio of ScH to gestational sacwas above 35% (p = 0.027). CONCLUSIONS: In the cases of subchorionic hematoma, we concluded that when the ratio of surrounding hematoma tothe gestational sac increased and when it was accompanied by nonspecific pelvic pain, the hospitalization period of thepatients increased and the ratio of pregnancy loss was higher.

Metabolic and carbohydrate characteristics of different phenotypes of polycystic ovary syndrome.

OBJECTIVE: To compare the prevalence of various metabolic and cardiovascular risk factors and insulin resistance between polycystic ovary syndrome (PCOS) patients with or without hyperandrogenism. MATERIAL AND METHODS: This is a retrospective cross-sectional study involving women with PCOS as diagnosed according to the Androgen Excess (AE) Society definition (n=504) and women with normoandrogenemic PCOS (n=183). Anthropometrics, lipid profile, glucose, insulin, oral glucose tolerance test (OGTT), and reproductive hormone levels were evaluated. RESULTS: Women with PCOS diagnosed according to the AE Society had a significantly higher prevalence of metabolic syndrome compared with the normoandrogenemic PCOS phenotype: odds ratio (OR) 2.95 [95% confidence interval (CI) 1.21-7.21]. There was no significant difference in the prevalence glucose intolerance test between the groups [OR: 2.15, 95% CI 0.71-6.56]. The prevalence of low high density lipoprotein (HDL)-cholesterol in the group under the AE-PCOS Society criteria was higher than that of the normoandrogenemic PCOS group [OR: 2.82, 95%CI 1.29-3.36]. CONCLUSION: The risks of metabolic syndrome and cardiovascular disease may vary among the phenotypes of PCOS based on the Rotterdam criteria. This new data may be of reference in informing women with PCOS, although further prospective studies are needed to validate this proposition.

Assessment of early decline in the percentage of ß-hCG values between days 0 and 4 after methotrexate therapy in ectopic pregnancy for the prediction of treatment success.

OBJECTIVE: To evaluate percentage changes in serum beta-human chorionic gonadotropin (ß-hCG) values between days 0-1, 0-4 and 0-7 as an indicator of methotrexate therapy success in extra-uterine pregnancies. MATERIAL AND METHODS: Women with ectopic pregnancy treated with single-dose methotrexate therapy between January 2011 and August 2012 were assessed. Recorded data were reviewed electronically from patient files. All women (n=93) with an ectopic pregnancy treated medically with intramuscular methotrexate (50 mg/m(2)) were included. The percentage changes in serum ß-hCG levels from day 0 to 1, day 0 to 4 and day 0 to 7 were calculated for each case. RESULTS: The median ß-hCG values decreased between days 0 and 4 by 55.8%, and 89.6% of these cases were treatment successes. The median initial serum ß-hCG values were lower in women with successful treatment, but this was not statistically significant (p=0.11). CONCLUSION: A decline in serum ß-hCG values between days 0 and 4 appears to be the best predictor. It would be beneficial to determine whether a woman with an ectopic pregnancy treated with single-dose methotrexate administration will be treated successfully.