Effects of uterus derived mesenchymal stem cells and their exosomes on asherman's syndrome.

Asherman's syndrome has become a growing problem with the incidence of cesarean and endometrial surgical procedures. A surgical procedure that can damage to the basal layer of the endometrium is formed as intrauterine adhesion and can cause asherman's syndrome. Mesenchymal stem cells (MSCs) are characterized by some characteristics such as non-immunogenic, angiogenic, antifibrotic, antiapoptotic and antiinflammatory properties, also they support tissue repair by secretion of various factors and chemokines in cellular therapy. Exosomes are active paracrine components with a great potential for repairing damaged tissue. Exosomes include many paracrine factors responsible for regeneration and angiogenesis. In this study, 10 newborn Wistar rats were used to obtain MSCs. A total of 24 adult Wistar rats were also used. The rats were divided into 4 groups: untreated control group; asherman control group; asherman + uterine-derived MSCs group; asherman + uterine-derived MSCs-exosomes group. At the end of the experiment, uterine tissues were evaluated by histochemical and immunohistochemical. As a result of MSCs and exosomes treatments, proliferation and vascularization in uterine tissue was increased. It was also shown to reduce fibrosis with masson's trichrome staining. MMP-2 and MMP-9 expression was enhanced by MSC and exosomal therapy; in addition, TIMP-2 expression was decreased. In our study, it was shown that proliferation and vascularization increased and fibrosis decreased in uterus as a result of MSC and exosome treatments. Our results indicate that the exosomal treatment restored the damage of asherman's syndrome at tissue at a shorter time than the MSCs group.

The ratio of anterior anogenital distance to posterior anogenital distance: A novel-biomarker for polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. The etiopathogenesis of the disease remains uncertain. Additionally, a full consensus has not been reached regarding PCOS diagnostic criteria. Several attempts have been made to diagnose PCOS with a simple clinical biomarker, but most of them failed. This study aims to investigate the possible association between PCOS and anogenital distance (AGD), which is an important sign of intrauterine androgen exposure. METHODS: A prospective cohort study was conducted on 130 women. The study group contained 65 women with PCOS whereas 65 healthy women were recruited for the control group, all between 18 and 40 years in age. The groups were compared in terms of demographics and clinical and laboratory parameters. Both anterior and posterior AGDs and associated ratios were recorded for each woman. RESULTS: The mean ratio of anterior AGD to posterior AGD for the PCOS and control group were 4.4 ± 1.0 and 4.9 ± 1.0, respectively (p = 0.003). Regression analysis demonstrated that this ratio significantly and positively correlated with the waist to hip ratio and negatively correlated with the free androgen index. CONCLUSION: AGD was initially used to define sexual differentiation of animals. Subsequent human studies showed that boys have longer AGDs than girls. Recent studies supporting the hypothesis that extreme prenatal androgen exposure contributes to PCOS found that AGD in adult PCOS patients was longer than control PCOS patients. However, a novel biomarker other than AGD needs to be identified to standardize these measurements. This work represents the first study to evaluate the ratio of anterior AGD to posterior AGD in PCOS patients. In this study, AGD anterior and posterior measurements were longer in PCOS patients than in controls. However, the strongest predictor of PCOS is the ratio of anterior to posterior AGD.

Determination of the effects of bone marrow derived mesenchymal stem cells and ovarian stromal stem cells on follicular maturation in cyclophosphamide induced ovarian failure in rats.

OBJECTIVE: Chemotherapy causes depletion of primordial follicles that leads to premature ovarian failure in female cancer survivals. We investigated the effect of bone marrow derived mesenchymal (BMMSCs) and ovarian stromal stem cells (OSSCs) on follicle maturation in chemotherapy induced ovarian failure. MATERIAL AND METHODS: Thirty six Wistar Albino female rats were divided into three groups. Cyclophosphamide at a dose of 200 mg/kg was intraperitoneally (IP) given to the rats in all groups two times. 4 × 106 BMMSCs (IP) was injected to the group-2 and 4 × 106 OSSCs (IP) was injected to the group-3. Serum Anti-Müllerian Hormone (AMH) levels was determined with ELISA and primordial follicles were counted for investigation of primordial follicle reserve. The ovarian structure were evaluated histomorphologically. Localization of BrdU labeled stem cells, the expression of the cell cycle regulator p34Cdc2, gap junction protein p-connexin43 and intraovarian regulators of folliculogenesis Bone Morphogenic Protein 6 and 15 (BMP-6 and BMP-15) were investigated by immunohistochemistry. RESULTS: The immunstaining of BMP-6 was higher in oocytes of group-3 more than group-1 and group-2. The immunpositivity of p34cdc2 and BMP-15 were also higher in follicular cells of group-3 than the other groups. The presence of p-connexin43 in group-3 was determined more than group-1 and group-2. The ovarian follicles with normal histological structure were observed just in group-3. Although, The AMH levels were decreased in rats from all groups at the end of experimental procedure the primordial follicle counts in group-3 was significantly higher than group-1. CONCLUSION: Our findings suggest that OSSCs have more protective effect on follicle maturation than BMMSCs in cyclophosphamide induced ovarian damage.

Ovulation Induction is a More Effective Stimulant on Antiovarian Antibody Production than In Vitro Fertilization.

INTRODUCTION: Our aim in this study is to evaluate the effects of in vitro fertilization (IVF), including controlled ovarian hyperstimulation (COH) and the number of oocyte pick-up (OPU) procedures on the development of anti-ovarian antibodies (AOA). METHODS: To evaluate the effects of IVF procedures, namely, COH and OPU, serum samples for measuring AOA concentration levels by enzyme-linked immunosorbent assay were collected on the third day of the menstrual cycle, at the end of the COH, and after OPU. RESULTS: The AOA levels in IVF patients were significantly higher than the fertile control groups'. In the IVF group, neither COH nor OPU caused any increase in AOA levels when compared to the basal results. AOA levels were higher in patients with a history of 5-8 cycles of ovulation induction, before IVF treatment. There was no relationship between the basal AOA concentrations and the type of infertility, the etiology of infertility or the pregnancy outcomes, whereas there was a relationship between the AOA and the duration of infertility. CONCLUSION: AOA levels of IVF patients were found to be higher than the fertile control groups'. AOA was found to be related to infertility in patients who had a longer duration of infertility and repeated ovulation induction procedures without IVF. COH and OPU during an IVF cycle did not cause an increase in AOA levels.

Melatonin causes regression of endometriotic implants in rats by modulating angiogenesis, tissue levels of antioxidants and matrix metalloproteinases.

PURPOSE: The aim of this study was to test if melatonin causes regression of endometriotic implants and whether it influences implant levels of superoxide dismutase (SOD), malondialdehyde (MDA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in rats. METHODS: Endometriotic implants were introduced surgically to 20 female Wistar albino rats, which were either treated with melatonin via intraperitoneal injection for four weeks (melatonin group, n = 10) or with saline (control group, n = 10) after a second-look laparotomies. The main outcome measures included volume (mm(3)) and weight (mg) of explants and tissue levels of SOD, MDA, VEGF, TIMP-2 and MMP-9. RESULTS: Before and after treatment implant volumes of the melatonin group were decreased significantly (P < 0.01) while there was no significant difference between the pretreatment and posttreatment implant volumes of the control group. Moreover, weight (P < 0.05) and histologic score (P < 0.05) of implants of the melatonin-treated rats were significantly lower than controls. Activity of SOD and TIMP-2 staining in melatonin group was significantly higher (both P < 0.01) while there were significant reductions in implant levels of VEGF and MMP-9 in melatonin group (both P < 0.01) than controls. CONCLUSIONS: Melatonin induces the regression of endometriotic implants in rats by modulating implant levels of SOD, MDA, VEGF, MMP-9 and TIMP-2.

Alterations of ionized and total magnesium levels in pregnant women with gestational diabetes mellitus.

BACKGROUND/AIMS: The aim of this prospective study was to determine ionized and total magnesium (Mg) levels in pregnant subjects with and without gestational diabetes mellitus (GDM). METHODS: Eighty-five women, 26-28 weeks pregnant, were recruited for routine oral glucose tolerance tests (OGTT); 45 had normal OGTT results and 40 were diagnosed with GDM. Electrolyte levels, including ionized and total Mg, were analyzed. RESULTS: Gestational age and BMI were similar between the two groups (p = 0.800, p = 0.025). Multivitamin use was higher in the control group (p = 0.036). Fasting blood glucose was higher in the GDM group (p < 0.001). The median total Mg levels were 1.9 mg/dl (range 1.6-2.2) in the control group and 1.8 mg/dl (range 1.2-2.1) in the GDM group (p < 0.001). The median ionized Mg levels were 0.5 mmol/l (range 0.4-0.6) in the control group and 0.4 mmol/l (range 0.4-0.5) in the GDM group (p < 0.001). CONCLUSION: Our study revealed a relationship between low total and ionized Mg levels and GDM, as in type 2 diabetes mellitus (DM). The literature regarding type 2 DM and our findings suggest that Mg is the key ion in the pathophysiology of GDM. Low-dose Mg supplementation was not related to GDM; however, pharmacological doses in the various stages of pregnancy could be beneficial and should be investigated.

Environmental Tobacco Smoke Exposure during Intrauterine Period, Promotes Caspase Dependent and Independent DNA Fragmentation in Sertoli-Germ Cells.

Objectives. To investigate the effect of cigarette smoke exposure during intrauterine period on neonatal rat testis. Methods. Twenty-five rats were randomized to be exposed to cigarette smoke with the Walton Smoking Machine or to room air during their pregnancies. The newborn male rats (n = 21) were grouped as group 1 (n = 15) which were exposed to cigarette smoke during intrauterine life and group 2 (n = 6) which were exposed to room air during intrauterine life. The orchiectomy materials were analyzed with TUNEL immunofluorescent staining for detection of DNA damage. To detect apoptosis, immunohistochemical analyses with caspase-3 were performed. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORES); secondary outcomes were Sertoli-cell count and birth-weight of rats. Results. Sertoli cell apoptosis was increased in group 1 (HSCORE = 210.6 ± 41.9) when compared to group 2 (HSCORE = 100.0 ± 17.8) (P = 0.001). Sertoli cell count was decreased in group 1 (P = 0.043). The HSCORE for the germ cells was calculated as 214.0 ± 46.2 in group 1 and 93.3 ± 10.3 in group 2 (P = 0.001) referring to an increased germ cell apoptosis in group 1. The apoptotic indexes for group 1 were 49.6 ± 9.57 and 29.98 ± 2.34 for group 2 (P = 0.001). The immunofluorescent technique demonstrated increased DNA damage in seminiferous epithelium in group 1. Conclusions. Intrauterine exposure to cigarette smoke adversely affects neonatal testicular structuring and diminishes testicular reserve.

Effect of stem cell application on Asherman syndrome, an experimental rat model.

PURPOSE: We evaluate the effect of stem cells to induce endometrial proliferation and angiogenesis on Asherman Syndrome (AS). METHODS: The experimental study was performed in stemcell research laboratory. Forty Wistar-Albino rats were divided according to groups. In group1 (n = 10) to establish the model; trichloroacetic acid was injected to right uterine horn. Two weeks later, intrauterine synechia was confirmed. In group2 (n = 10), 2 weeks later, 2 × 106 mesenchymal stem cells (MSC) were injected into right uterine horn followed by three intraperitoneal injections of MSCs. In group3 (n = 10), daily oral estrogen was initiated on the second week. In group4 (n = 10), MSC injections and oral estrogen was given together. The amount of fibrosis, vascularisation, inflammation and immunohistochemical staining with vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and Ki-67 were evaluated in the uterine tissues. RESULTS: In all treatment groups; fibrosis decreased but vascularisation and immunhistohemical stainings increased in the experimental side. The amount of fibrosis, vascularisation, Ki-67 and PCNA scores were similar between group2 and 3. In group4, comparing to group2, less fibrosis but more Ki-67, PCNA and VEGF staining was observed. CONCLUSION: Stem cells, when added to estrogen, are a highly effective alternative to induce regeneration of endometrium in Asherman Syndrome therapy.

Effect of injectable medroxyprogesterone acetate and etonogestrel implants on GABA-A and serotonin receptors in white and gray matter of the brain: experimental study in rats.

The aim of this study was to evaluate the time-dependent effect of progesterone-only contraceptives on the brain and to obtain an improved understanding of mood disorders experienced under this medication. A total of 66 Wistar albino rats were divided into three groups: etonogestrel (ENG) implant (group 1, n = 30); depot medroxyprogesterone acetate (MPA)-injectable (group 2, n = 30); and control (group 3, n = 6) groups. Groups 1 and 2 were each divided into five subgroups, which were examined every 10 d for up to 50 d after medication administration, to evaluate its time-dependent effect. There was no difference in terms of gamma-aminobutyric acid (GABA) and serotonin immunohistochemical staining in white and gray matter among the subgroups of group 1. In group 2, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on day 50, when compared to the control group (p = 0.041). When the subgroups of group 2 were compared, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on days 40 and 50 when compared to day 10. In conclusion, we showed that ENG and MPA have no effect on apoptosis and GABA-A receptors in the brain. We also showed that MPA has time-dependent effects on serotonin receptors, which may be a possible mechanism involved in mood disorders during long-term usage of injectable progesterone-only contraceptives.

Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived mesenchymal stem cells during puberty.

OBJECTIVE: In female cancer survivors, the accelerated loss of primordial follicles may lead to premature ovarian failure. We investigated the protective effects of bone marrow derived mesenchymal stem cells (BMMSC) and gonadotropin releasing hormone analogue (GnRHa) against chemotherapeutic-induced ovarian toxicity in a rat model. MATERIAL AND METHODS: Forty-eight Wistar albino female rats were divided into four groups. Group 1 was composed of rats that were given 200 mg/kg cyclophosphamide injection for each cycle (two cycles for each rat). Both cyclophosphamide and 0.4 µg GnRHa were administered to Group 2. Cyclophosphamide and 4 million/kg BMMSC were administered to Group 3. Cyclophosphamide, GnRHa, and BMMSC were administered to Group 4. Germ cell apoptosis, DNA fragmentation and primordial follicular count were investigated with Cleave Caspase-9 and TUNEL analysis. The presence of the SRY gene on the Y chromosome in the ovary of the recipient female rats was checked with PCR. RESULTS: Immunohistochemical staining (IHS) of Caspase-9 and TUNEL was higher in Group 1 than in Group 3 (p < 0.05). Similarly, Group 4 had higher values than Group 3 (p < 0.05). The presence of the SRY gene was detected in Groups 3 and 4 with the PCR analysis. The mean primordal follicle count was lowest in Group 1 and the mean primordial follicle counts were higher in Groups 2 and 3 than in Group 1. The difference between Group 1 and Group 4 was not significant. CONCLUSION: BMMSC therapy was found to be protective from germ cell apoptosis and DNA damage when it was used with chemotherapy regimens including alkylating agents.

Time dependent influence of etonogestrel on the caspase-3 immunoreactivity and apoptotic indexes of rat uterus and ovaries.

Apoptosis is necessary for the balance between cell proliferation and loss. Thirty-six Wistar-Albino rats were subjected to investigate apoptotic effect of widely used implantable progestins on ovarian and uterine tissues. Rats were divided into 6 groups. In the first five groups, we applied etonogestrel (IMP) subcutaneous implants (n = 30). The rats in groups were sacrificed sequentially every 10 days after application. The rats in the last group (n = 6) were accepted as controls. Apoptotic index (AI) values and Caspase-3 immunoreactivities of ovaries and uterus were recorded. In IMP groups, AI and Hscore values in stroma and glandular epithelium of uterus, granulosa and teca-lutein cells of the ovary increased with the longer progesterone exposure. Increase in AI and Hscore values were more prominent after 30 days of exposure for teca-lutein cells of ovary. Progestins increased apoptosis in ovaries and uterus by the longer exposure. Apoptosis increased in ovaries by chronic progesterone exposure. The apoptotic effect of progestin on endometrium is clear but long-term systemic application may lead to alterations in ovarian physiology. We evaluated time dependent apoptotic effect of etonogestrel on reproductive physiology and discussed progestins effect from another point of view in this study.

Environmental tobacco smoke exposure during intrauterine period promotes granulosa cell apoptosis: a prospective, randomized study.

OBJECTIVE: To evaluate the intrauterine effect of cigarette smoke on cell death and DNA damage in follicular cells of fetal ovarian tissue. METHODS: A prospective, randomized study was conducted with 25 female wistar-albino rats. The rats were randomized to be exposed either to cigarette smoke or to room air, initiating from proestrous period and during pregnancy. Newborn female rats were categorized as Group 1 (n = 24) that had been exposed to cigarette smoke during intrauterine life and Group 2 (n = 7) that had been exposed to room air during intrauterine life. Bilateral ooferectomies were performed on the 2nd week of their life. TUNEL (in-situ Terminal Deoxynucleotidyl-Transferase Mediated dUTP-Nick-End Labeling) immunofluorescent staining and immunohistochemical analyses with caspase-3 were used for detection of DNA damage and apoptosis. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORE). Secondary outcomes were ovarian follicle counts and birth weights of newborn rats. RESULTS: There was a significant increase of HSCORE and apoptotic index in Group 1. Increased immunofluorescent staining; evaluating DNA damage, with TUNEL method was observed in granulosa cells in Group 1. CONCLUSIONS: Intrauterine exposure to cigarette smoke diminishes ovarian reserve of female offspring, raising the concern about the generational impact of maternal smoking on ovarian function in the human.

Regression of endometrial autografts in a rat model of endometriosis treated with etanercept.

OBJECTIVE: To determine the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in the rat endometriosis model. STUDY DESIGN: A randomized, placebo-controlled, blinded study using rat endometriosis model. After the peritoneal implantation of endometrial tissue, twenty-eight Wistar female rats were randomized to two equal intervention groups: the control group and the etanercept-treated group. After measuring implant volume, pretreatment blood and peritoneal fluid samples were obtained. A vehicle treatment of 2 mL saline to the rats in control group and 0. 4 mg/kg etanercept SC once weekly were administered in the etanercept-treated group. After four weeks treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate preservation of epithelia. Endometrial explants were evaluated immunohistochemically for tumor necrosis factor receptor type 2 (TNFR2). A scoring system was used to evaluate expression grade of TNFR2. RESULTS: There was not a significant difference in spherical volume between control (131.0 (60.3-501.2)) and treatment groups (72.8 (31.2-149.6)) (p>0.025). There was a significant change in between the volumes of implants before and after treatment in etanercept group (p<0.05). At the end of the treatment significant differences among the groups were found in histopathological and immunohistochemical parameters (p<0.05) also histologic scores and HSCORES were decreased in the treatment group significantly (p<0.05). CONCLUSION: These results indicate that etanercept was found to effectively reduce the development of endometriosis in this experimental rat model.

Anti-Mullerian hormone is a better marker than inhibin B, follicle stimulating hormone, estradiol or antral follicle count in predicting the outcome of in vitro fertilization.

OBJECTIVE: The present study aims to compare anti-Mullerian hormone (AMH) with other ovarian reserve markers and to find a cut-off value of AMH for predicting ovarian response towards controlled ovarian hyperstimulation in an in vitro fertilization (IVF) program. MATERIALS AND METHODS: A prospective analysis was performed in 180 patients undergoing their first IVF trial, which is being conducted at a department of assisted reproduction in a tertiary medical center. The main outcome measures were determined as age and antral follicle count as well as the serum concentrations of follicle stimulating hormone, luteinizing hormone (LH), estradiol (E2), inhibin B and AMH. The predictive power of the aforementioned measures in specifying ovarian response was determined by means of discriminate analyses. RESULTS: As expected, day 3 LH levels were significantly high in the poor responder group. The poor responders had significantly lower antral follicle counts, retrieved oocyte number, and mature oocyte counts as well as day 3 AMH levels (5.8 ± 2.32 vs. 1.8 ± 0.80 ng/ml). There was a positive correlation with antral follicle count, basal AMH, E2 and follicle count on the day of HCG administration and negative correlation with age. The AMH level was addressed as the only significant factor in determination of mature oocyte number. A cut-off point for serum AMH concentration indicating the value of 2.97 ng/ml was found to predict the poor ovarian response with a sensitivity of 100.0% and a specificity of 89.6%. However, the same cut-off point was not as predictive for the non-conception circumstance. CONCLUSION: The present study concludes that AMH is a promising biochemical marker for the prediction of ovarian response and that a cut-off point indicating the value of 2.97 ng/ml can be adopted for this prediction.

Effect of bevacizumab on postoperative adhesion formation in a rat uterine horn adhesion model and the correlation with vascular endothelial growth factor and Ki-67 immunopositivity.

We investigated whether adhesion formation is prevented by the inhibition of angiogenesis in a rat uterine horn adhesion model. A single-dose of bevacizumab was effective in preventing postoperative intraperitoneal adhesion formation among 30 Wistar albino rats that underwent serosal injury by use of a standard technique after laparotomy with intraperitoneal bevacizumab.

Rehabilitation of irradiated patients with modified and conventional sandblasted acid-etched implants: preliminary results of a split-mouth study.

PURPOSE: The aim of this study was to evaluate the success rate of chemically modified and conventional sandblasted acid-etched surface (SLA) titanium implants in irradiated oral squamous cell carcinoma patients. MATERIAL AND METHODS: Twenty patients with a mean age of 61.1 years were treated with dental implants after ablative surgery and radio-chemotherapy of oral cancer. All patients were non-smokers. The placement of SLA and modSLA implants was performed bilaterally according to a split-mouth design. All 102 implants (50 SLA, 52 modSLA) placed showed an unloaded healing time of 6 weeks in the mandible and 10 weeks in the maxilla. Mean crestal bone changes using standardized orthopantomographies and clinical parameters like pocket depths, mPII and mBI were evaluated. RESULTS: Of 102 implants, 55 implants (27 SLA implants, 28 modSLA) were located in the maxilla and 47 implants (23 SLA, 24 modSLA) in the mandible. The average observation period was 14.4 months. The amount of bone loss at the implant shoulder of SLA implants was 0.4 mm mesial and 0.4 mm distal. The modSLA implants displayed a bone loss of mesial 0.3 mm and distal 0.3 mm. Two SLA implants were lost resulting in a success rate of 96%. The success rate of modSLA implants was 100%. CONCLUSION: Regarding the data found in this investigation, we can conclude that implants with chemically modified and conventional SLA titanium surface show high success rates in irradiated patients. SLA implants with or without a chemically modified surface regardless of the location can be restored with a high predictability of success at least in the short time range observed.

Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment.

Our aim was to evaluate the optimal treatment strategy addressing cardiovascular risk in obese and nonobese patients with polycystic ovary syndrome (PCOS). We planned a prospective randomized clinical study. Normoandrogenemic and oligoamenorrheic women with PCOS and impaired glucose tolerance (n = 96) were enrolled in the study. Six months of treatment with metformin HCL or oral contraceptive pills (OCPs) were given to the patients. Group 1 were obese and receiving metformin. Group 2 were obese and receiving OCPs. Group 3 were nonobese and receiving metformin, and Group 4 were nonobese receiving OCPs. ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated. ADMA, homocysteine, hs-CRP and HOMA-IR were similar in obese and nonobese groups before the treatment. After 6 months of treatment, a significant decrease was observed in ADMA, homocysteine and HOMA-IR levels in Groups 1 and 3. An increase in ADMA and hs-CRP levels was observed in Groups 2 and 4. In this study, metformin treatment leads to improvement in hormonal and metabolic parameters and decreases ADMA and homocysteine levels possibly independent of BMI. However, the use of oral contraceptives in obese and nonobese patients with PCOS with impaired glucose tolerance increases ADMA and hs-CRP levels and creates an increase in the metabolic risk.

Predictive value of middle cerebral artery to uterine artery pulsatility index ratio in preeclampsia.

OBJECTIVE: To determine the predictive value of middle cerebral artery (MCA) to uterine artery pulsatility index (PI) ratio in preeclamptic patients. METHODS: This prospective cross-sectional study was performed on 64 preeclamptic and 131 normal pregnancies at or beyond 26 weeks of gestation between June 2007-August 2008 in the high-risk pregnancy unit of Dr. Zekai Tahir Burak Women Health Teaching and Research Hospital, Ankara. Doppler blood flow velocimetry of the uterine and umbilical arteries and fetal MCA was measured. The ratios between the PI of MCA and the mean PI value of both uterine arteries were calculated and values below the fifth percentile were considered as brain-sparing. The ratios between the PI of MCA and PI of the umbilical artery were calculated and values lower than 1.08 were considered as brain-sparing and the results were related to perinatal outcome. Statistical analysis were performed using the SPSS Software (SPSS, Chicago, IL, USA) version 9.0 for Windows. Odds ratio with 95% confidence interval (95%) was also used for statistical analysis. RESULTS: In 11 (42.3%) of the preeclamptic pregnancies that had abnormal MCA/uterine artery PI, 4 of them had severe preeclampsia and 7 had mild preeclampsia. In the low MCA/uterine artery PI ratio group, a statistically significantly higher rate of Cesarean section (66 vs. 88.46%), NICU admission (26.3 vs. 57.6%), preterm birth (52.6 vs. 92.3%) was found. Abnormal MCA/uterine artery PI ratio and abnormal MCA/umbilical artery PI ratio in the prediction of adverse outcome of pregnancy was compared. In the prediction of preterm birth, which was better for the MCA/uterine artery, there was a significant difference between the ratios (P = 0.005). CONCLUSION: Our results suggest that MCA/uterine artery PI ratio is a good predictor of neonatal outcome in preeclamptic patients in the third trimester and could be used to identify fetuses at risk of morbidity and mortality.

Efficacy of anti-tumor necrosis factor therapy on endometriosis in an experimental rat model.

OBJECTIVE: To show the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in an experimental model. DESIGN: A randomized, placebo-controlled, blinded study using rat endometriosis model. SETTING: Experimental research center of Ankara Education and Research Hospital. ANIMAL(S): Twenty-two Wistar female rats. INTERVENTION(S): After peritoneal implantation of endometrial tissue, rats were randomized to two equal intervention groups: control and etanercept-treated groups. After measuring implant volume, blood and peritoneal fluid samples were obtained. Vehicle treatments of 2 mL saline to rats in control and 0.4 mg/kg etanercept SC once weekly were administered in treatment group. Four weeks later, a third laparotomy was performed to remeasure implant volumes, blood, and peritoneal fluid samples. MAIN OUTCOME MEASURE(S): To compare spherical volume, peritoneal fluid and serum levels of VEGF, IL-6, and TNF-α between groups. RESULT(S): There was a significant difference in spherical volume between control [131.0 (60.3-501.2)] and treatment groups [72.8 (31.2-149.6)] (p < 0.025). In etanercept-treated group, a significant difference was found between peritoneal fluid and serum levels of VEGF, IL-6, and TNF-α (p < 0.01). CONCLUSION(S): These results indicate that etanercept was found to effectively reduce the development of endometriosis.